Limbic+System

> **Limbic System Overview** > > Buried within the depths of the cerebrum are several large aggregates of limbic structures and nuclei which are preeminent in the control and mediation of memory, emotion, learning, dreaming, attention, and arousal, and the perception and expression of emotional, motivational, sexual, and social behavior including the formation of loving attachments.The structures and nuclei of the limbic system are exceedingly ancient, some of which began to evolve over 450 million years ago. Over the course of evolution, these emotional structures have expanded in size, some becoming increasingly cortical in response to increased environmental opportunities and demands. In fact, as the neocortical forebrain expanded and until as recently as 50 million years ago, the cerebrum of the ancestral line that would eventually give rise to humans, was dominated by the limbic system. Indeed, the old limbic brain has not been replaced and is not only predominant in regard to all aspects of motivational and emotional functioning, but is capable of completely overwhelming "the rational mind" due in part to the massive axonal projections of limbic system to the neocortex. > > > **FUNCTIONAL OVERVIEW** > > In general, the primary structures of the limbic system include the hypothalamus, amygdala, hippocampus, septal nuclei, and anterior cingulate gyrus; structures which are directly interconnected by massive axonal pathways. > > The hypothalamus could be considered the most "primitive" aspect of the limbic system, though in fact the functioning of this sexually dimorphic structure is exceedingly complex. The hypothalamus regulates internal homeostasis including the experience of hunger and thirst, can trigger rudimentary sexual behaviors or generate feelings of extreme rage or pleasure. In conjunction with the pituitary the hypothalamus is a major manufacturer/secretor of hormones and other bodily humors, including those involved in the stress response and feelings of depression. > > The amygdala has been implicated in the generation of the most rudimentary and the most profound of human emotions, including fear, sexual desire, rage, religious ecstasy, or at a more basic level, determining if something might be good to eat. The amygdala is implicated in the seeking of loving attachments and the formation of long term emotional memories. It contains neurons which become activated in response to the human face, and which become activated in response to the direction of someone else's gaze. The amygdala also acts directly on the hypothalamus via the stria terminalis, medial forebrain bundle, and amygdalafugal pathways, and in this manner can control hypothalamic impulses. The amygdala is also directly connected to the hippocampus, with which it interacts in regard to memory. > > The hippocampus is unique in that unlike other structures, almost all of its input from the neocortex is relayed via the overlying entorhinal cortex. The hippocampus is exceedingly important in memory, acting to place various short-term memories into long-term storage. Presumably the hippocampus encodes new information during the storage and consolidation (long-term storage) phase, and assists in the gating of afferent streams of information destined for the neocortex by filtering or suppressing irrelevant sense data which may interfere with memory consolidation. Moreover, it is believed that via the development of long-term potentiation the hippocampus is able to track information as it is stored in the neocortex, and to form conjunctions between synapses and different brain regions which process and store associated memories. > > The septal nuclei is in part an evolutionary and developmental outgrowth of the hippocampus, and the hypothalamus, and links these two structures along with the brainstem. It consists of both lateral and medial segments; i.e. the lateral and medial septal nuclei. Presumably these interconnections allow the septal nuclei to exert modulatory influences on hippocampal regarding memory functioning and arousal. The septal nuclei is also interconnected with and shares a counterbalancing relationship with the amygdala, particularly in regard to hypothalamic activity and emotional and sexual arousal. For example, whereas the amygdala promotes indiscriminate contact seeking, and perhaps promiscuous sexual activity, the septal nuclei inhibits these tendencies thus assisting in the formation of selective and more enduring emotional attachments. > The septal nuclei can produce extremes of emotion, including explosive violence, known as "septal rage." > > The anterior cingulate is considered a transitional cortex, or mesocortex. It is intimately interconnected with the hypothalamus, amygdala, septal nuclei, and hippocampus, and participates in memory and emotion including the experience of pain, misery, and anxiety. The evolution and expression of maternal behavior is also directly related to this structure. The anterior cingulate is also the most vocal aspect of the brain, becomes active during language tasks, and generates emotional-melodic aspects of speech which is expressed via interconnections with the right and left frontal speech areas, and the vocalization center in the midbrain periaqueductal gray. Thus, the anterior cingulate is implicated in the more cognitive aspects of social-emotional behavior including language and the establishment of long term attachments beginning with the mother-infant bond. > > The olfactory bulb and olfactory system are also implicated in the functioning of the limbic system. The limbic striatum (nucleus accumbens, olfactory tubercle, substantia innominata, ventral caudate and putamen), the orbital frontal and inferior temporal lobes and the midbrain monoamine system. These systems and structures are also directly connected or separated by only a single synapse, and which tend to become aroused not only as a function of emotional arousal, but in reaction to olfactory input which continues to exert profound effects on the human limbic system, and upon human behavior.

> HYPOTHALAMUS > The hypothalamus is an exceedingly ancient structure and unlike most other brain regions it has remained somewhat similar in structure throughout phylogeny and apparently over the course of evolution. Located in the most medial aspect of the brain, along the walls and floor of the 3rd ventricle, this nucleus is fully functional at birth and is the central core from which all emotions derive their motive force. Indeed, the hypothalamus is highly involved in all aspects of emotional, reproductive, vegetative, endocrine, hormonal, visceral and autonomic functions and mediates or exerts significant or controlling influences on eating, drinking, sleeping and the experience of pleasure, rage, and aversion. > In fact, almost every region of the cerebrum interacts with and communicates with the hypothlamus and is subject to its influences. Moreover, the hypothalamus utilizes the blood supply to transmit hormonal and humoral messages to peripheral organs as well as other brain structures and utilizes the blood supply to receive information as well, thus bypassing the synaptic route utilized by almost all other regions of the neuroaxis. Through the blood supply (as well as via the cerebrospinal fluid), the hypothalamus not only regulates, but is subject to feedback regulation by the same structures that it controls. > Certain areas of the diencephalon, midbrain, and brainstem, are exceedingly exceedingly sensitive to hormones, humors, and peptides circulating within the blood plasma, and the cerebrospinal fluids; chemosensory information which is used for maintaining homeostasis. Broadly considered, these chemosensory sensitive areas are generally located near or surrounding the cerebral ventricles (Johnson & Gross, 2013) and they tend not to be effected by the so called "blood brain barrier;" referred to as circumventricular organs (CVOs). There are perhaps dozens of CVO's at least 8 of which are located in or near the ventricular systems which feed the brainstem and diencephalon including the hypothalamus, pineal gland and pituitary (Johnson & Gross, 2013). > The hypothalamus, however, does not act solely through the blood supply or via cerebrospinal fluid, and its also receives sensory information synaptically, and often indirectly, as is the case with the majority of olfactory fibers. In general, sensory stimuli reach the hypothalamus from a variety of routes. These include the solitary tract of the brainstem, a structure which receives, processes, and transmits data received principally from the vagus and glosopharyngeal cranial nerves. Through this pathway the lateral hypothalamus is informed about cardivocascular activities, respiration, and taste. These pathways are also bidirectional (Swanson, 2007). Other major pathways include the medial forebrain bundle (which contains axons from a variety of different cellular groups) and the stria terminalis through which the amygdala and hypothalamus interact. The hypothalamus also maintains massive interactive pathways with the frontal lobes and septal nuclei (Risvold & Swanson, 2012). > Broadly considered, the hypothalamus consists of three longitudinal subdivisions which extend along its anterior to posterior axis. These are the medial, lateral, and periventricular (Swanson, 2007). The periventricular zone is concerned with neuroendocrine regulation, whereas the lateral and medial zones are concerned with affective states, including hunger and thirst. These zones, in turn can be further subdivided into subnuclei. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Phylogenetically, structurally, and embryologically the hypothalamus is traditionally considered part of the diencephalon. During embryological development it emerges from the diencephalic vessicle of the neural tube along with those anterior-lateral evaginations which become the optic nerves and retina of the eye, as well as the pituitary gland (ventrally) and the pineal gland and thalamus (dorsally). There is some dispute, however, over the developmental patterns of the hypothalamus, as some scientists believe that it develops from the outside in (the "hollow hypothalamus hypothesis"). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">On the other hand, the hypothalamus originates from the medially situated neuroepithelium, and thus begins its developmental journey in a medial (or rather paramedial) to lateral arc, such that it appears that the medial hypothalamus is fashioned (and matures) in advance of the lateral hypothalamus. > > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">From an evolutionary perspective, however, the hypothalamus appears to have dual (forebrain - midbrain) origins; that is emerging from the dorsal (visual) midbrain, and the olfactory forebrain, which together, and over the course of evolution, gave rise to the ventral, medial, lateral and preoptic hypothalamus. Nevertheless, in modern mammals and humans, the olfactory origins are no longer directly apparent, particularly in that most olfactory fibers reach the hypothalamus indirectly; e.g. via the amygdala and piriform cortex. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The hypothalamus is exceedingly responsive to olfactory (and pheromonal) input. Perhaps reflecting this partial and putative olfactory origin is the fact that this structure utilizes chemical (hormonal, humoral) molecules to communicate with other areas of the brain, and reacts to these same molecules as well as olfactory cues, including those directly related to sexual status. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is this olfactory-chemical origin and sensitivity which in turn may explain why portions of the hypothalamus (like the amygdala) are also sexually dimorphic and reacts to pheromonal sensory stimuli including those which signal sexual status. That is, structurally and functionally the hypothalamus of males and females are stucturally dissimilar (Bleier et al. 1982; Dorner, 1976; Gorski et al. 1978; Rainbow et al. 1982; Raisman & Field, 1971, 1973) and perform different functions depending on if one is a man or a woman, and if a woman is sexually receptive, pregnant, or lactating. For example, the sexually dimorphic supraoptic and paraventricular nuclei project (via the infundibular stalk) to the posterior lobe of the pituitary which may then secrete oxytocin--a chemical which can trigger uterine contractions as well as milk production in lactating females (and which can thus make nursing a pleasurable experience). The male hypothalamus/pituitary does not perform this function. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">SEXUAL DIMORPHISM IN THE HYPOTHALAMUS > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As is well known, sexual differentiation is strongly influenced by the presence or absence of gonadal steriod hormones during certain critical periods of prenatal development in many species including humans. Not only are the external genitalia and other physical features sexually differentiated but certain regions of the brain have also been found to be sexually dimorphic and differentially senstitive to steriods, particularly the preoptic area and ventromedial nucleus of the hypothalamus, as well as the amygdala. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Indeed it has now been well established that the amygdala and the hypothalamus (specifically the anterior commissure, anterior-preoptic, ventromedial and suprachiasmatic nuclei) are sexually differentiated and have sex specific patterns of neuronal and dendritic development. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">This is a consequence of the presence or absence of testosterone during fetal development in humans, or soon after birth in some species such as rodents. Specifically, the presence or absence of the male hormone, testosterone during this critical neonatal period, directly effects and determines the growth and pattern of interconnections between the amygdala and hypothalamus, between axons and dendrites in these nuclei as well as the hippocampus, septal nuclei, olfactory system (ref), and thus the organization of specific neural circuits. In the absence of testosterone, the female pattern of neuronal development occurs. Indeed, it is the presence or absence of testosterone during these early critical periods that appear to be responsible for neurological alterations which greatly effect sex differences in thinking, sexual orientation, aggression, and cognitive functioning > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, if the testes are removed prior to differentiation, or if a chemical blocker of testosterone is administered thus preventing this hormone from reaching target cells in the limbic system, not only does the female pattern of neuronal development occur, but males so treated behave and process information in a manner similar to females (e.g., Joseph et al. 1978); i.e. they develop female brains and think and behave in a manner similar to females. Conversely, if females are administered testosterone during this critical period, the male pattern of differentiation and behavior results (see Gerall et al. 1992 for review). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">That the preoptic and other hypothalamic regions are sexually dimorphic is not surprising in that it has long been known that this area is extremely important in controlling the basal output of gonadotrophins in females prior to ovulation and is heavily involved in mediating cyclic changes in hormone levels (e.g. FSH, LH, estrogen, progesterone). Chemical and electrical stimulation of the preoptic and ventromedial hypothalamic nuclei also triggers sexual behavior and even sexual posturing in females and males (Hart et al., 2005; Lisk, 1967, 1971) and, in female primates, even maternal behavior (Numan, 2005). In fact, dendritic spine density of ventromedial hypothalamic neurons varies across the estrus cycle (Frankfurt et al., 1990) and thus presumably during pregnancy and while nursing. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In primates, electrical stimulation of the preoptic area increases sexual behavior in males, and significantly increases the frequency of erections, copulations and ejaculations, we well as pelvic thrusting followed by an explosive discharge of semen even in the absence of a mate (Hart, et al., 2005; Maclean, 1973). Conversely, lesions to the preoptic and posterior hypothalamus eliminates male sexual behavior and results in gonadal atrophy. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Hence, it is thus rather clear than the ability to sexually reproduce is dependent on the functional integrity of the hypothalamus. In fact, it is via the hypothalamus acting on the pituitary, that gonadotropins come to be released. Gonadotropins control the production and/or release of gametes; i.e. ova and sperm. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, the hypothalamic neurons secrete gonadotropin-releasing hormone, which acts on the anterior lobe of the pituitary which secretes gonadotropins. However, given that in females, this is a cyclic event, whereas in males sperms are constantly reproduced, is further evidence of the sexual dimorphism of the hypothalamus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Although the etiology of homosexuality remains in question, it has been shown that the ventromedial and anterior nuclei of the hypothalamus of male homosexuals demonstrate the female pattern of development (Levay, 1991; Swaab, 1990). When coupled with the evidence of male vs female and homosexual differences in the anterior commissure which links the temporal lobe and sexually dimorphic amygdala (see below) as well as the similarity between male homosexuals and women in regard to certain cognitive attributes including spatial-perceptual capability (see below), this raises the possibility that male homosexuals are in possession of limbic system that is more "female" than "male" in functional as well as structural orientation. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is also interesting to note that the sexually dimorphic preoptic region contains thermosensitive neurons, and controls the physiological and behavior responses to excessive external cold or heat. That is, it is responsible for internal thermoregulation and thus heat loss or retention (Alam et al., 2011). Although we can only speculate, it may well be sex differences in this structure which accounts (at least in part) for the stereotypical differences in male vs female perceptions of cold, and why, stereotypically, females (despite their extra-layers of heat-retaining fat) are more likely to insist on elevating room temperature. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">LATERAL & VENTROMEDIAL HYPOTHALAMIC NUCLEI > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Although consisting of several nuclear subgroups, the lateral and medial (ventromedial) hypothalamic nuclei play particularly important roles in the control of the automonic nervous system, the experience of pleasure and aversion, eating and drinking, and raw (undirected) emotionality. They also appear to share a somewhat antagnistic relationship. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">For example, the medial hypothalamus controls parasympathetic activities (e.g. reduction in heart rate, increased peripheral circulation) and exerts a dampening effect on certain forms of emotional/motivational arousal. The lateral hypothalamus mediates sympathetic activity (increasing heart rate, elevation of blood pressure) and is involved in controlling the metabolic and somatic correlates of heightened emotionality (Smith et al. 1990). In this regard, the lateral and medial region act to exert counterbalancing influences on each other. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">HUNGER & THIRST > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The lateral and medial region are highly involved in monitoring internal homeostasis and motivating the organism to respond to internal needs such as hunger and thirst (Anand & Brobeck, 1951; Bernardis & Bellinger 2007; Hetherington & Ranson, 1940). For example, both nuclei appear to contain receptors which are sensitive to the body's fat content (lipostatic/caloric receptors) and to circulating metabolites (e.g. glucose) which together indicate the need for food and nourishment. For example, when food is digested, the viscera secretes various hormones which act on the alimentary tract, which in turn stimulates the solitary tract (ST) which projects directly to the hypothalamus. However, in the absence of food, the viscera also begins to secrete various hormones which when coupled changes in caloric blood levels, signals to the hypothalamus the need for food. The lateral hypothalamus also appears to contain osmoreceptors (Joynt, 1966) which determine if water intake should be altered. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Electophysiologically, it has been determined that the hypothalamus not only become highly active immediately prior to and while the organism is eating or drinking, but the lateral region alters it's activity when the subject is hungry and simply looking at food (Hamburg, 1971; Rolls et. al., 1976). In fact, if the lateral hypothalamus is electrically stimulated a compulsion to eat and drink results (Delgado & Anand, 1953). Conversely, if the lateral area is destroyed bilaterally there results aphagia and adipsia so severe animals will die unless force fed (Anand & Brobeck, 1951; Hetherington & Ranson, 1940; Teitelbaum & Epstein, 1962). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">If the medial hypothalamus is surgically destroyed, inhibitory influences on the lateral region appear to be abolished such that hypothalamic hyperphagia and severe obesity result (Anand & Brobeck, 1951; Hoebel & Tetelbaum, 1966; Teitelbaum, 1961). Hence, the medial area seems to act as a satiaty center; but, a center that can be overridden. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, with ventromedial lesions, animals not only eat more, but the intervals between meals becomes shorter such that they eat more meals. Thus they begin to gain weight. In part this is also due to changes in the sympathetic nervous system which increases vagal activity, thus signaling the need for more food. As noted, the ST is bidirectional. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Normally the hypothalamus can act via the ST and thus the vagal complex and can signal satiation. However, with medial destruction, the ST becomes hyperactive thus inducing parasympathetic overactivity which induces more rapid gastric emptying and the rapid storage of ingested calories. Because these calories are rapidly stored, caloric blood levels are reduced and the lateral hypothalamus is stimulated to begin eating again--which explains the increased frequency of meals. In fact, if animals that have become obese following ventromedial lesions are starved back to their normal weight, once they are allowed free access to food, they again become obese.

<span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Overall, it appears that the lateral hypothalamus is involved in the intitation of eating and acts to maintain a lower weight limit such that when the limit is reached the organism is stimulated to eat. Conversely, the medial regions seems to be involved in setting a higher weight limit such that when these levels are approached it triggers the cessation of eating. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In part, these nuclei exert these differential influences on eating and drinking via motivational/emotional influences they exert on other brain nuclei (e.g. via reward or punishment). However, it should be stressed that there are a number of other structures and hormones and peptides involved, including the pancreatic islets, and insulin secretion. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">PLEASURE & REWARD > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In 1952, Heath reported what was then considered remarkable. Electrical stimulation near the septal nuclei elicited feelings of pleasure in human subjects: "I have a glowing feeling. I feel good!" Subsequently, Olds and Milner (1954) reported that rats would tirelessly perform operants to receive electrical stimulation in this same region and concluded that stimulation "has an effect which is apparently equivalent to that of a conventional primary reward." Even hungry animals would demonstrate a preference for self-stimulation over food. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Feelings of pleasure (as demonstrated via self-stimulation) have been obtained following excitation to a number of diverse limbic areas including the olfactory bulbs, amygdala, hippocampus, cingulate, substantia nigra (a major source of dopamine), locus coeruleus (a major source of norepinephrine), raphe nucleus (serotonin), caudate, putamen, thalamus, reticular formation, medial forebrain bundle, and orbital frontal lobes. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In mapping the brain for positive loci for self-stimulation, Olds (1956) found that the medial forebrain bundle (MFB) was a major pathway which supported this activity. Although the MFB interconnects the hippocampus, hypothalamus, septum, amygdala, orbital frontal lobes (areas which give rise to self-stimulation), Olds discovered in its course up to the lateral hypothalamus reward sites become more densely packed. Moreover, the greatest area of concentration and the highest rates of self-stimulatory activity were found to occur not in the MFB but in the lateral hypothalamus (Olds, 1956; Olds & Forbes, 1981). Indeed, animals "would contine to stimulate as rapidly as possible until physical fatigue forced them to slow or to sleep" (Olds, 1956). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Electrophysiological studies of single lateral hypothalamic neurons indicate that these cells become highly active in response to rewarding food items (Nakamura & Ono, 1986). In fact, many of these cells will become aroused by neutral stimuli repeatedly associated with reward such as a cue-tone --even in the absence of the actual reward (Nakamura & Ono, 1986; Ono et al. 1980). However, this ability to form associations appears to be secondary to amygdaloid activation (Fukuda et al. 2007) which in turn influences hypothalamic functioning. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Nevertheless, if the lateral region is destroyed the experience of pleasure and emotional responsiveness is almost completely attenuated. For example, in primates, faces become blank and expressionless, whereas if the lesion is unilateral, a marked neglect and indifference regarding all sensory events occurring on the contralateral side occurs (Marshall & Teitelbaum, 1974). Animals will in fact cease to eat and will die. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">AVERSION > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In contrast to the lateral hypothalamus and it's involvement in pleasurable self-stimulation, activation of the medial hypothalamus is apparently so aversive that subjects will work to reduce it (Olds & Forbes, 1981). Hence, electrical stimulation of the medial region leads to behavior which terminates the stimulation--apparently so as to obtain relief (e.g. active avoidance). In this regard, when considering behavior such as eating, it might be postulated that when upper weight limits (or nutritional requirements) are met, the medial region becomes activated which in turn leads to behavior (e.g. cessation of eating) which terminates its activation. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is possible, however, that medial hypothalamic activity may also lead to a state of quiescence such that the organism is motivated to simply cease to respond or to behave. In some instances this quiescent state may be physiologically neutral, whereas in other situations medial hypothalamic activity may be highly aversive. Quiescence is also associated with parasympathetic activity which is mediated by the medial area. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">HYPOTHALAMIC DAMAGE & EMOTIONAL INCONTINENCE: LAUGHTER & RAGE > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">When electrically stimulated, the hypothalamus responds by triggering two seemly oppositional feeling states, i.e. pleasure and unpleasure/aversion. The generation of these emotional reactions in turn influences the organism to respond so as to increase or decrease what is being experienced. > The hypothalamus, via it's rich interconnections with other limbic regions including the neocortex and frontal lobes, it able to mobilize and motivate the organism to either cease or continue to behave. Nevertheless, at the level of the hypothalamus, the emotional states elicited are very primitive, diffuse, undirected and unrefined. > The organism feels pleasure in general, or aversion/unpleasure in general. Higher order emotional reactions (e.g. desire, love, hate, etc.) require the involvement of other limbic regions as well as neocortical participation. > > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Emotional functioning at the level of the hypothalamus is not only quite limited and primitive, it is also largely reflexive. For example, when induced via stimulation, the moment the electrical stimulus is turned off the emotion elicited is immediately abolished. In contrast, true emotions (which require other limbic interactions) are not simply turned on or off but can last from minutes to hours to days and weeks before completely dissipating. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Nevertheless, in humans, disturbances of hypothalamic functioning (e.g. due to an irritating lesion such as tumor) can give rise to seemingly complex, higher order behavioral-emotional reactions, such as pathological laughter and crying which occurs uncontrollably. However, in some cases when patients are questioned, they may deny having any feelings which correspond to the emotion displayed (Davison & Kelman, 1939; Ironside, 1956; Martin, 1950). In part, these reactions are sometimes due to disinhibitory release of brainstem structures involved in respiration, whereas in other instances the resulting behavior is caused by hypothalamic triggering of other limbic nuclei. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">UNCONTROLLED LAUGHTER > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Pathological laughter has frequently been reported to occur with hypophyseal and midline tumors involving the hypothalamus, aneurysm in this vicinity, hemorrhage, astrocytoma or pappiloma of the 3rd ventricle (resulting in hypothalamic compression), as well as surgical manipulation of this nucleus (Davison & Kelman, 1939; Dott, 1938; Foerster & Gabel, 1933; Martin, 1950; Money & Hosta, 1967; Ironside, 1956; List, Dowman, & Bagheiv, 1958). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, Martin (1950, p.455) describes a man who while "attending his mother's funeral was seized at the graveside with an attack of uncontrollable laughter which embarrassed and distressed him considerably." Although this particular attack dissipated, it was soon accompanied by several further fits of laughter and he died soon thereafter. Post-mortem a large ruptured aneurysm was found, compressing the mammillary bodies and hypothalamus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In a similar case (Anderson, 1936; Cited by Martin, 1950), a patient literally died laughing following the eruption of the posterior communicating artery which resulted in compression (via hemorrhage) of the hypothalamus. "She was shaken by laughter and could not stop: short expirations followed each other in spasms, without the patient being able to make an adequate inspiration of air, she became cyanosed and nothing could stop the spasm of laughter which eventually became noiseless and little more than a grimace. After 24 hours of profound coma she died." > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Because laughter in these instances has not been accompanied by corresponding feeling states, this pseudo-emotional condition has been referred to as "sham mirth" (Martin, 1950). However, in some cases, abnormal stimulation in this region (such as due to compression effects from neoplasm) has triggered corresponding emotions and behaviors -- presumably due to activation of other limbic nuclei. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, laughter has been noted to occur with hilarious or obscene speech--usually as a prelude to stupor or death--in cases where tumor has infiltrated the hypothlamus (Ironside, 1956). In several instances it has been reported by one group of neurosurgeons (Foerster & Gagel, 1933) that while swabbing the blood from the floor of the 3rd ventricle, patients "became lively, talkative, joking, and whistling each time the infundibular region of the hypothalamus was manipulated." In one case, the patient became excited and began to sing. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">HYPOTHALAMIC RAGE > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Stimulation of the lateral hypothalamus can induce extremes in emotionality, including intense attacks of rage accompanied by biting and attack upon any moving object (Flynn et al. 1971; Gunne & Lewander, 1966; Wasman & Flynn, 1962). If this nucleus is destroyed, aggressive and attack behavior is abolished (Karli & Vergness, 1969). Hence, the lateral hypothalamus is responsible for rage and aggressive behavior. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">As noted, the lateral maintains an oppositional relationship with the medial hypothalamus. Hence, stimulation of the medial region counters the lateral area such that rage reactions are reduced or eliminated (Ingram, 1952; Wheately, 1944), whereas if the medial is destroyed there results lateral hypothalamic release and the triggering of extreme savagery. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In man, inflammation, neoplasm, and compression of the hypothalamus have also been noted to give rise to rage attacks (Pilleri & Poeck, 1965), and surgical manipulations or tumors within the hypothalamus have been observed to elicit manic and rage-like outbursts (Alpers, 1940). These appear to be release phenomenon, however. That is, rage, attack, aggressive, and related behaviors associated with the hypothalamus appears to be under the inhibitory influence of higher order limbic nuclei such as the amygdala and septum (Siegel & Skog, 1970). When the controlling pathways between these areas are damaged (i.e. disconnection) sometimes these behaviors are elicited. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, Pilleri and Poeck (1965) described a man with severe damage throughout the cerebrum including the amygdala, hippocampus, cingulate, but with complete sparing of the hypothalamus who continually reacted with howling, growling, and baring of teeth in response to noise, a slight touch, or if approached. Hence, the hypothalamus being released responds reflexively in an aggressive-like non-specific manner to any stimulus. Lesions of the frontal-hypothalamic pathways have been noted to result in severe rage reactions as well (Fulton & Ingraham, 1929; Kennard, 1945). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Nevertheless, like "sham mirth", rage reactions elicited in response to direct electrical activation of the hypothalamus immediately and completely dissipate when the stimulation is removed. As such, these outbursts have been referred to as "sham rage". > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">CIRCADIAN RHYTHM GENERATION & SEASONAL AFFECTIVE DISORDER > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">As noted in chapter 5, during the initial stages of cerebral evolution, the dorsal hypothalmus (like the dorsal thalamus, dorsal hippocampus, dorsal midbrain) was likely fashioned, at least in part, from photosensitive cells located in the anterior head region. Given the daily and seasonal changes in light vs darkness, nuclei in the midbrain-pons, and in the hypothalamus, became sensitive to and capable of generating rhythmic hormonal, neurotransmitter, and motoric activities. It is the hypothalamus, however, the suprachiasmatic nucleus (SCN) in particular, which appears to be the "master clock" for the generation of circadian rhythms; rhythms which have a period length of 24 hours (Aronson et al. 2013; Morin 2014).

<span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In humans and other species, the SCN (and the midbrain superior colliculus) is a direct recipient of retinal axons. It also receives indirect visual projections from the lateral geniculate nucleus of the thalamus (see Morin 2014). In this regard, the visual system appears to act to synchronize the SCN (and probably the midbrain-pons) to function in accordance with seasonal and day to day variations in the light/dark ratio. However, the SCN does not "see" per se, nor can it detect visual features, as its main concern is adjusting mood, and activity in regard to light intensity as related to rhythm generation. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">There is thus some evidence which suggests that when the SCN of the hypothalamus is deprived of (or unable to effectively respond to) sufficient light, although rhythm generation is not grossly effected (Morin 2014), individuals may become depressed; a condition referred to as Seasonal Affective Disorder (SAD). That is, the hypothalamus (and midbrain-pons) appear to decrease those hormonal and neurochemical activities normally associated with activation and high (daytime) activity thus resulting in depression. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, the hypothalamic-pituitary axis secretes melatonin in phase with the circadian rhythm. Phase-delayed rhythms in plasma melatonin secretion have been repeatedly noted in most (but not all) studies of individuals with SADs (see Wirz-Justice et al. 2013, for review). However, with light therapy, not only is the depression relieved but the melatonin secretions return to normal. This is significant for melatonin is derived from tryptophan via serotonin and low serotonin levels have been directly linked to depression (e.g. Van Pragg 1982). <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">There is some evidence which suggests that the hypothalamus (and the midbrain) may act to regulate serotonin release within the brainstem, which in turn may explain why serotonin levels rhythmically fluctuate (e.g. such as during the sleep cycle), or become abnormal when denied sufficient light; i.e. the production of serotonin by the raphe nucleus (in the pons) is abnormally effected. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">On the other hand, numerous studies have reported that SADs and major depression occurs most often during the Spring and not the winter, and is not influenced by latitude. There is also some suggestion that abnormal temperature perception, or aging within the SCN may be responsible for the genesis of SADs and related depressive disorders. For example, age related changes in the SCN have been noted to adversely effect circadian rhythm generation as well as metabolic and peptide activity (Aronson et al. 2013). In consequence, rest vs active cycles also become abnormal, with reductions in arousal and activity; i.e. the patient becomes depressed. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is also possible, however, that although light therapy can assist in alleviating depressive symptoms associated with SADs, that the deregulation of the SCN (and melatonin/serotonin) might be unrelated to light, temperature, or aging, but may be a consequence of stress on the hypothalamus. For example, the hypothalamic-pituitary axis is tightly linked with and in fact mediates stress induced alterations in serotonin; as well as norepinephrine which has also been repeatedly implicated in the genesis of depression. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">THE HYPOTHALAMUS-PITUITARY-ADRENAL AXIS > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The hypothalamic, pituitary, adrenal system (HPA) is critically involved in the adaption to stressful changes in the external or internal environment. For example, in response to fear, anger, anxiety, disapointment, and even hope, the hypothalamus begins to release corticotropin releasing factor (CRF) which activates the andenohypophysis which begins secreting ACTH which stimulates the adrenal cortex which secretes cortisol (Fink, 2009). > These events in turn appear to be under the modulating influences of norepinephrine. That is, as stress increases, NE levels decrease, which triggers the activation of the HPA axis. As is well known, low levels of NE are associated with depression. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Normally, cortisol secretion is subject to the tonic influences of NE; whereas cortisol can indirectly reduce NE synthesis. Thus a feedback system is maintained via the interaction of these substances (in conjuction with ACTH). Moreover, cortisol and NE levels fluctuate in reverse, and thus maintain a reciprocal relationship with the circadian rhythm; i.e. in oppositional fashion they increase and then decrease throughout the day and evening. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Among certain subgroups suffering from depression, it appears that this entire feedback regulatory system and thus the HPA axis is disrupted (Carrol et al. 1976; Sachar et al. 1973). This results in the hypersecretion of ACTH and cortisol with a corresponding decrease in NE; which results in NE induced depression. It was these findings which led to the development of the Dexamethasone suppression test over 25 years ago. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Via the administration of Dexamethasone (a synthetic corticosteroid) it was determined that many depressed individuals have excess cortisol, and an increased frequency of cortisol secretory episodes (Carrol et al. 1976; Sachar et al. 1973; Swann et al. 2014). Moreover, those who demonstrate excess cortisol were found to respond to NE potentiating agents, whereas those who were depressed but with normal cortisol, responded best to serotonin potentiating compounds (Van Pragg 1982). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is also noteworthy that dexamethason nonsuppression rates are increased in mania; specifically "mixed manic" states which consist of lability, grandiosity, and lability superimposed over depression. These "mixed manic" individuals also display elevated NE levels but respond poorly to lithium and show higher levels of cortisol during the depressed phase of their illness. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted, the hypothalamus may greatly influence circadian activities within the midbrain and pons, and thus the rhythmical secretion of various neurotransmitters. For example, corticotropin-releasing factor acts directly on the locus coeruleus (Valentino et al. 1983) which manufactures NE, and on the raphe thereby influencing serotonin release. These findings suggest a disturbance in circadian or rhythmical control of hypothalamic and midbrain-pontine activity can give rise to depression, or mixed mania in some individuals; women in particular. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Lateralization. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Although scant, there is some evidence which suggests that the right hypothalamus may be more heavily involved in the control of neuroendocrine functioning, particularly in females. Females are also far more likelyt to suffer from depression and from SADs. Moreover, right cerebral dysfunction can reduce NE levels in both the right and left hemisphere. Greater right hypothalamic concentration of substances such as LHRH (luteinizing hormone) has also been reported, which in turn is a "female" hormone involved in lactation and pregnancy. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">PSYCHIC MANIFESTIONS OF HYPOTHALAMIC ACTIVITY: THE ID > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Phylogenetically and from an evolutionary perspective, the appearance and development of the hypothalamus predates the differentation of all other limbic nuclei, e.g., amygdala, septal nucleus, hippocampus (Andy & Stephan, 1961; Brown, 1983; Herrick, 1925; Humphrey, 1972). It constitutes the most primitive, archaic, reflexive, and purely biological aspect of the psyche. > Biologically the hypothalamus serves the body tissues by attempting to maintain internal homeostasis and by providing for the immediate discharge of tenions in an almost reflexive manner. Hence, as based on studies of lateral and medial hypothalamic functioning, it appears to act reflexively, in an almost on/off manner so as to seek or maintain the experience of pleasure and escape or avoid unpleasant, noxious conditions. > Emotions elicited by the hypothalamus are largely undirected, short-lived, being triggered reflexively and without concern or understanding regarding consequences; that is, unless chronically stressed or aroused. Nevertheless, direct contact with the real world is quite limited and almost entirely indirect as the hypothalamus is largely concerned with the internal environment of the organism. Although it receives and responds to light, it cannot "see." It has no sense of morals, danger, values, logic, etc., and cannot feel or express love or hate. Although quite powerful, hypothalamic emotions are largely undifferentiated, consisting of feelings such as pleasure, unpleasure, aversion, rage, hunger, thirst, etc. > As the hypothalamus is concerned with the internal enviornment much of it's activity occurs outside conscious-awareness. Moreover, being involved in maintaining internal homeostasis, via, for example, it's ability to reward or punish the organism with feelings of pleasure or aversion, it tends to serve what Freud (1911) has described as the pleasure principle. > > THE PLEASURE PRINCIPLE > The lateral and medial nuclei exert counterbalancing influences which serve to modulate activity occurring in the other. As described by Freud (1911), the pleasure principale not only serves to maximize pleasant experiences, but acts to keep the psyche as a whole free from high levels of excitation (be they pleasurable or unpleasant). > Like the hypothalamus, the pleasure principle is present from birth and for some time thereafter the search for pleasure is manifested in an unrestricted manner and with a great deal of intensity as there are no oppositional forces (except those between the lateral and medial regions) to counter it's strivings. Indeed, higher order limbic nuclei have yet to mature. > Functionally isolated, the hypothalamus at birth has no way of reducing tension or mobilizing the organism for any form of effective action. It is helpless. When tensions associated with immediate needs (e.g. hunger or thirst) become unpleasant the only response available to the hypothalamus is to cry and make rage-like vocalizations. When satiated, the hypothalamus can only respond with a feeling state suggesting pleasure or at least quiescence. Indeed, as is well known, for the first few months of life the infants awareness largely consists of a very restricted matrix involving tactile, visceral (hunger) and kinesthetic sensations, where emotionally the infant is capable of screaming, crying, or demonstrating very rudimentary features of pleasure, i.e. an attitude of acceptance of quiescence. > It is only with the further differentiation and maturation of higher order limbic nuclei (e.g. amygdala, septal nucleus, hippocampus) that the infant begins to achieve some awareness of external reality and begins to form memories as well as differentiate and associate externally occurring events and individuals. > > AMYGDALA > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In contrast to the primitive hypothalamus, the more recently developed amygdala (the "almond") is preeminent in the control and mediation of all higher order emotional and motivational activities. Via it's rich interconnections with various neocortical and subcortical regions, amygdaloid neurons are able to monitor and abstract from the sensory array stimuli that are of motivational significance to the organism. This includes the ability to discern and express even subtle social-emotional nuances such as friendliness, fear, love, affection, distruct, anger, etc., and at a more basic level, determine if something might be good to eat. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In fact, amygdaloid neurons respond selectively to the flavor of certain preferred foods, as well as to the sight or sound of something that might be especially desirable to eat including even the sight of drugs that induce extreme pleasure. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, it has been shown, using positron emission tomography, that detoxified cocaine users not only respond to a cocaine video with cocaine craving, but with increased amygdala (and anterior cingulate) activity. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">elying its involvement in emotion, including the pleasure associated with cocaine usage, is the unique chemical anatomy of the amygdala, which is rich in a variety of neuropetides including enkephalins and beta-endorphins as well as opiate receptors (Atweh & Kuhar, 1977; Fallon & Ciofi, 1992; Uhl et al. 1978). In fact, of all brain regions, the greates concentration of opiate receptors is found within the human amygdala. Other chemical systems include lutenizing hormone, vasopressin, somatostatin, and corticotropin releasing factor (Fallon & Ciofi, 1992) --indications of its involvement in stress and sexuality, especially female sexuality. The primate amygdala is sexually differentiated with male and female patterns of dendritic organization and steroid activity. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The amygdala is exceedingly responsive to social and emotional stimuli as conveyed vocally, through touch, sight, and via the expressions of the face. In fact, the amygdala, as well as the overlying (and partly coextensive) temporal lobe, contains neurons which respond selectively to smiles and to the eyes, and which can differentiate between male and female faces and the emotions they convey. For example, the left amygdala acts to discriminate the direction of another person's gaze, whereas the right amygdala becomes activated while making eye-to-eye contact. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, the normal human amygdala typically responds to frightened faces by altering its activity, whereas injury to the amygdala disrupts the ability to recognize faces. With bilateral destruction, emotional speech production and the capacity to respond appropriately to social emotionally stimuli is abolished. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">ingle amygdaloid neurons receive a considerable degree of topographic input, and are predominatly polymodal, responding to a variety of stimuli from different modalities simultaneously (Amaral et al. 1992; O'Keefe & Bouma, 1969; Ono & Nishijo, 1992; Perryman, Kling, & Lloyd, 2007; Rolls 1992; Sawa & Delgado, 1963; Schutze et al. 2007; Turner et al. 1980; Ursin & Kaasa, 1960; Van Hoesen, 1981). The amygdala is also very sensitive to somesthetic input and physical contact such that even a slight touch in a very circumscribed area of the body can produce amygdaloid excitation. Overall, because emotional, motivational, and multimodal assimilation of various sensory impressions occurs in this region, it is also involved in attention, learning, and memory (Gloor, 2010; Halgren, 1992; LeDoux, 2012). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, through the massive interconnections maintained with the lateral and medial (ventromedial) hypothalamus, the amygdala is able to act directly on this structure, driving the hypothalamus, so to speak, and thus tapping into its emotional reserviour so that its ends may be met. Indeed, it is able to modulate hypothalamic activity through inhibitory and excitatory projections to this structure. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Direct stimulation of the basolateral amygdala and the ventral amydalofugal pathway excites the principle neurons of the medial hypothalamus. By contrast, stimulation of the medial (ventro-medial) amygdala and the stria terminalis pathway, inhibits these same hypothalamic neurons. Hence, whereas the lateral amydala exerts excitatory influences on the hypothalamus, the medial amygdala exerts inhibitory influences, and can thus control, or at least exert excitatory/inhibitory and thus modulatory influences on hunger, thirst, sexual arousal, rage, etc., as well as hormonal, endocrine, and other functions associated with the hypothalamic nuclues. Indeed, the amygdala can be likened to the chief executive of the limbic system and weilds enormous power via its control over the hypothalamus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, in the cat and monkey, stimulation of the border area between the lateral and medial hypothalamus can trigger aggressive defensive reactions. As indicated by radioactive tracers, both the lateral and medial amygdala projection to this area. And, when the amygdala is electrically activated, the hypothalamus becomes activated, and defensive and aggressive reactions can be triggered. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, this system is also interactional, especially in regard to sexual activity, fear, anger, hunger, and stress. For example, the hypothalamus can stimulate the amygdala which may then survey the environment so that internal needs may be met, and/or they may act in concert regarding sexual behavior, the stress response, and so on. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">OVERVIEW: AMYGDALA STRUCTURAL FUNCTIONAL ORGANIZATION > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The amygdala is buried within the depths of the anterior-inferior temporal lobe and consists of several major nuclear groups including what has been referred to as the "extended amygdala." These include the cortical-medial, central, paralaminar, lateral, basal, and acessory basal nucleus. Different authors propose different divisions and link them differently. For example, Stephan and Andy assign the cortical division to the basolateral amydala, and the central division to the medial division. Price et al., subdivided the amygdala into basolateral, corticomedial and central amygdaloid nuclei. Others propose yet different schemes. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">For our purposes we will primarily focus on the "medial" and the basolateral subdivisions. The phylogenetically ancient medial group (or cortico-medial amygdala) is involved in olfaction, sexual, and motor activity (via its interconnections with the striatum), and the relatively newer basolateral division (lateral amygdala) is most fully developed in primates and humans. Of its various subdivisions, the basolateral amygdala is the most "cortex-like. However, being allocortex it contains three layers (vs 7 for the neocortex) with layer 2 containing pyramidal neurons which rely on excitatory neurotransmitters, e.g., glutamate--whereas the local-circuit (interneurons) rely on the inhibitory transmitters, e.g., GABA. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The lateral amydala utilizes the ventral amygdalofugal pathway and less so the stria terminalis to influence the hypothalamus. The lateral amygdala also relies on the medial forebrain bundle which is the pathway subserving the pleasure circuit. By contrast, the medial amygdala relies on the stria terminalis, and less so the amygdalofugal pathway to influences the hypothalamus. Through these pathways, these diferent subdivions of the amygdala can act to modulate activity in the hypothalamus, septal nuclei, and other subcortical structures. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Evolution & Embryology > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In humans, the right amygdala is also larger than the left amygdala, with the basolateral portion contributing to most of this asymmetry. Moreover, over the course of evolution, and in the transition from amphibians to reptiles, to mammals and then humans, the basolateral amygdala appears to have grown the most in size as compared to other amygdaloid nuclei--that is, when considered only in regard to its subtemporal diminsions. However, it also appears that the medial amygdala may have contributed to the evolution of the piriform cortex, and then the evolution of the 4 to 5 layered mesocortex, which when layered upon the 3-layered allocortical piriform cortex, gave rise to the neocortex of the temporal lobe. Hence, the expansion of the medial amydala may not be apparent as that expansion is represented as mesocortex and neocortex. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, it appears that the medial group was broken up over the course of evolution such that structures such as the claustrum, became separated and is now situated beneath the auditory cortex of the superior temporal lobe. Indeed, the claustrum which is very cortical in organization, may well act as an interface between the auditory cortex and the amygdala, processing and relaying auditory impulses to and fro, and may have, in addition to the medial amygdala, contributed to the evolution of the auditory cortex. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The amygdala, therefore, has definitely increased in size over the course of evolution, and has become increasingly cortical, has contributed to the evolution of mesocortex and neocortex (which is thus a cortical extension of the neocortex, maintaining extensive interconnections). In addition, the right amygdala is larger than the left which in turn may contribute to right hemisphere dominance for emotion. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Intrinsic & Extrinsic Organization: The Flow of Information > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Like the lateral and medial hypothalamus, the medial and basolateral (hereafter referred to as the lateral) amygdaloid nuclei subserve different functions and maintain different anatomical interconnections. And, they can be subdivided into additional subnuclei. As noted, they also contain pyramidal neurons which are excitatoryand use glutamate and which project throughout the neocortex as well as to the hippocampus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Local circuit neurons are mostly stellate-like and chandelier cells, which account for about 30% of the amydala's neurons and which use the inhibitory transmitter GABA. Considered rather broadly and simplistically, these local circuit neurons are organized in such a fashion that they appear to project information from the the lateral to the basal amygdala, and from the lateral basal to the medial and central amygdala which transmits, via pyramid and local-circuit neurons to the uncus, piriform cortex, medial temporal cortex, entrohinal cortex, anterior hippocampus, and via pyramidal neurons to the striatum, the septal nuclei, hypothalamus, cingulate, medial dorsal nucleus of the thalamus, brainstem, and throughout the frontal and temporal lobes. However, the lateral amygdala also projects to the septal nuclei, hypothalamus, corpus striatum, dorsal medial thalamus, brainstem, and throughout the neocortex via pyramidal axons <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">It appears that much of the input from the neocortex is directed at the lateral amygdala (the exception being auditory cortex which also projects to the medial amygdala). Hence, in certain respects, at least at the level of the neocortex, it appears that there is an almost circular stream of activity, from lateral/basal to medial/central to neocortex to lateral/basal. However, subcortically, both the lateral and medial project to many of the same exact structures, often providing counterbalancing excitatory/inhibitory influences. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, the amygdala receives significant projections directly from the olfactory bulb. In act, "the olfactory system is the only sensory system in which first- and second-order central sensory neurons project directly to the amygdala". Moreover, it receives projections from the gustatory system. Smell and taste thus converge in the amygdala, which may explain why some patients with temporal lobe epilepsy experience terrible odors and tasts as part of the aura which announces the onset of a seizure. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In addition, the secondary and in particular the association and multi-modal assimilation areas, including the orbital frontal lobe, project directly to the amygdala. In addition, as is evident from dissecting the human brain, the amygdala maintains significant reciprocal connections with the primary auditory area and Wernicke's area--and similar projections are evident in primates. Hence, this structure receives simple and complex auditory, as well as fully formed perceptions from the neocortex which feeds the amygdala this information which it then analyzes for social, sexual, gustatory, and emotional significance. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The Amygdala-Striatum > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Emybryologically, the medial amygdala is the first portion of the basal ganglia (limbic) striatal complex to appear during development, being formed via neuroblast migration from the epithilium of the lateral ventricle. Specifically, around the sixth week of fetal development immature neuroblasts migrate in massive numbers from the ventricular lining, and congregate in the more caudal portion of the emerging forebrain, thus forming an arc shaped "striatal ridge" from which the primordial amygdala and striatum will emerge. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Approximately one week after the formation of the amygdala, this primordial amygdala-striatum begins to differentiate and balloon outward to also create the striatum. That is, both the striatum and amygdala are derived from the arc shaped "striatal ridge," the caudal portion giving rise to the primordial amgydala at about the 6th week of gestation, and the basal portion later giving rise to the primordial striatum which initially overlies and is contiguous with the amygdala <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Thus initially these structures are contiguous. However, over the ensuing weeks, these structures are pushed apart as the forebrain and its interconnections form. However, although they are pushed apart and may even break up into semi-separate islands (or rather, penninsulas) the amgydala maintains connnections with what is referred to as the "extended amygdala," i.e., the limbic striatum and through what is called the "tail of the caudate" maintains massive interconnections with the corpus striatum > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, the tail of the caudate nucleus (as it circles in an arc from the frontal to temporal lobe) terminates and merges with the medial and in particular, the lateral amygdala. Hence, the lateral amygdala has also been referred to the "striatum limitans, and the "striatum accessorium". > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">By contrast,the medial amygdala (or rather, the central division of the medial amygdala, central-medial amygdala) extends almost imperceptibly around the fundus of the entorhinal sulcus, and merges with the substantia innominata of the limbic striatum. The amygdala, therefore, is in fact part of the basal ganglia and is heavily involved in motivating and coordinating gross, or whole body motor activity via the striatum. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">THE MEDIAL AMYGDALA > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The medial amygdala receives fibers from the olfactory tract, and via a rope of fibers called the stria terminalis projects directly to and receives fibers from the medial hypothalamus (via which it exerts inhibitory influences) as well as the septal nucleus. The stria terminals is significantly larger and thicker in males vs females which suggests that information and impulse exchange (or inhibition) between the hypothalamus and amygdala is different in men vs women. Moreover, in humans, the amygdala in general is large in males than in females, and in primates, the medial amygdala is sexually differentiated, such that the male amygdala contains a greater number of synaptic connections and shows different patterns of steroidal activity. In fact, the human amygdala is 16% larger in the male in total volume whereas in male rats, the medial amygdala is 65% larger than the female amygdala and grows or shrinks in the presence of testosterone. > The female medial amygdala is a principle site for uptake of the female sex hormone, estrogen, and contains a high concentration of leutenizing hormones which are important during pregnancy and nursing. In fact, the female medial amygdala fluctuates immunoreactive activity during estrus cycle, being highest during proestrus. Moreover, the medial amygdala projects directly to the ventromedial hypothalamus and the preoptic area of the hypothalamus which, as noted above, are sexually differentiatedand which when activated produce sex specific behaviors and, in primates, even maternal behavior. These amygdala to hypothalamic synapses are excitatory. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Because the medial amygdala is sexually differentiated, and through its massive connections with the hypothalamus and preoptic area, as well as the striatum which controls gross motor and limb movements, when activated, male vs female sexual behavior can be triggered. These amygdala-induced sexual behariors include sexual posturing, penile erection and clitoral tumenence, thrusting, sexual moaning, ejaculation, as well as ovulation, uterine contractions, lactogenetic responses, and orgasm. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In addition, the medial (and lateral) regions are rich in cells containing enkephalins, and opiate receptors can be found throughout the amygdala and the amygdala becomes exceedingly active when experiencing a craving for pleasure inducing drugs, such as cocaine. In this regard, the amygdala is capable of inducing extreme feelings of pleasure as well as motivating the individual to engage in pleasure-seeking behaviors such as sexual activity. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">LATERAL AMYGDALA > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">With the evolutionary ascent of primates the lateral division of the amygdala progressively expands and differentiates. The lateral amygdala contributes fibers to the stria terminalis and gives rise to the amygdalofugal pathway via which it projects to the lateral and medial hypothalamus (upon which it exerts inhibitory and excitatory influences respectively), the dorsal medial thalamus (which is involved in memory, attention and arousal), the limbic and corpus striatum, as well as other subcortical regions including the brainstem. Lateral amygdala brainstem projection pathways include the dopamine producing substantia nigra, the vocalizing periaqueductal gray, the pontine tegmentum which includes and area that triggers the startle response as well as visceral nuclei such as those controlling blood pressure, respiration, vosodilation and constriction and so on. It also sends some fibers into the spinal cord, where they travel along with those of the pyramidal tract. It also receives fibers from the medial forebrain bundle which in turn has it's site of origin in the lateral hypothalamus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In general, whereas the medial amygdala is highly involved in motor, olfactory and sexual functioning, the lateral division is intimately involved in all aspects of emotional activity. Hence, it's rich interconnections with the lateral and medial hypothalamus, and the neocortex and those brainstem centers controlling the visceral aspects of affective-motor behavior. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The lateral amygdala maintains rich interconnections with the inferior, middle, and superior temporal lobes, as well as the insular temporal region, which in turn allows it to sample and influence the auditory, somesthetic, and visual information being received and processed in these areas, as well as scrutinize this information for motivational and emotional significance. Gustatory and respiratory sense are also re-represented in this vicinity as is the capacity to influence (via sensory analysis) food and water intake. The lateral division also maintains rich interconnections with cingulate gyrus, orbital and medial frontal lobes and the parietal cortex through which it able to influence emotional expression and receive complex somesthetic information. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The lateral amygdala is highly important in analyzing information received and transferring information back to the neocortex so that further elaboration may be carried out at the neocortical level. It is through the lateral division that emotional meaning and significance can be assigned to as well as extracted from that which is experienced. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The amygdala, overall, maintains a functionally interdependent relationship with the hypothalamus. It is able to modulate and even control rudimentary emotional forces governed by the hypothalamic nucleus. However, it also acts as the behest of hypothalamically induced drives. For example, if certain nutritional requirements need to be meet, the hypothalamus signals the amygdala which then surveys the external enviornment for something good to eat or drink. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">On the other hand, if the amygdala via environmental surveilance were to discover a potentially threatening stimulus, it acts to excite and drive the hypothalamus so that the organism is mobilized to take appropriate action. as noted, direct stimulation of the basolateral amygdala and the ventral amydalofugal pathway excites the principle neurons of the ventromedial hypothalamus (Dreifuss, et al., 1968). When the hypothalamus is activated by the amygdala, instead of responding in an on/off manner, cellular activity continues for an appreciably longer time period. The amygdala can tap into the reservoir of emotional energy mediated by the hypothalamus so that certain ends may be attained.\ > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">ATTENTION > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The amygdala acts to perform environmental surveilance and can trigger orienting responses as well as mediate the maintanance of attention if something of interest or importance were to appear. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In part, the attention response can be triggered by amygdala activation of the brainstem, frontal lobes, and the dorsal medial nucleus (DMN) of the thalamus, each of which is implicated in arousal (see chapter 19). The DMN, for example, in conjunction with the frontal lobe, acts to gate and regulate the flow of information destined for the neocortex (Joseph, 2009a). The amydala, being provided thalamic, brainstem, as well as neocortical input (as well as projecting to these nuclei), is therefore able to directly influence the DMN so that attention can be directed to particular percepts (and emotional significance attached). In fact, the projections of the amygdala to extend well beyond the DMN, but extends throughout the thalamus, as well as throughout the neocortex. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Electrical stimulation of the lateral amygdala, therefore, can initiate quick and/or anxious glancing and searching movements of the eyes and head such that the organism appears aroused and highly alert as if in expectation of something that is going to happen. The EEG becomes desynchronized (indicating arousal), heart rate becomes depressed, respiration patterns change, and the galvanic skin response significantly alters and the animal may freeze -- reactions which characteristically accompany the orienting response of most species. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Once a stimulus of potential interest is detected, the amygdala then acts to analyze its emotional-motivational importance and will act to alert other nuclei such as the hypothalamus, brainstem, and striatum, so that appropriate action may take place. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">FEAR, RAGE & AGGRESSION > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Initially, electrical stimulation of the amygdala produces sustained attention and orienting reactions. If the stimulation continues the subject may begin to experience, wariness, fear and/or rage (Cendes et al. 2014; Davis et al., 2010; Gloor 1992; Halgren 1992; LeDoux, 2012; Rosen & Schulkin, 2012; Ursin & Kaada, 1960). When fear follows the attention response, the pupils dilate and the subject will cringe, withdraw, and cower. This cowering reaction in turn may give way to extreme fear and/or panic such that the animal will attempt to take flight. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Among humans, the fear response is one of the most common manifestations of amygdaloid electrical stimulation and abnormal activation. Moreover, unlike hypothalamic on/off emotional reactions, attention and fear reactions can last up to several minutes after the stimulation is withdrawn. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In addition to behavioral manifestations of heightened emotionality, amygdaloid stimulation can result in intense changes in emotional facial expression. This includes crying and facial contortions such as baring of the teeth, dilation of the pupils, widening or narrowing of the eye-lids, flaring of the nostrils, as well as sniffing, licking, and chewing. Indeed, some of the behavioral manifestations of a seizure in this vicinity (i.e. temporal lobe epilepsy) typically include throat and mouth movements, including chewing, smacking of the lips, licking, and swallowing--a consequence, perhaps of amygdala activation of the brainstem periaqueductal gray and nuclei subserving mastication. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In many instances patients or animals will react defensively and with anger, irritation, and rage which seems to gradually build up until finally the animal or human will attack. Unlike hypothalamic "sham rage", amygdaloid activation results in attacks directed at something real, or, in the absence of an actual stimulus, at something imaginary. There have been reported instances of patient's suddenly lashing out and even attempting to attack those close by, while in the midst of a temporal lobe seizure (Saint-Hilaire et al., 1980), and/or attacking, kicking, and destroying furniture and other objects (Ashford et al., 1980). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, rage and attack will persist well beyond the termination of the electrical stimulation of the amygdala. In fact, the amygdala remains electrophysiologically active for long time periods even after a stimulus has been removed (be it external-perceptual, or internal-electrical) such that is appears to contine to process--in the abstract--information even when that information is no longer observable (O'Keefe & Bouma, 1969). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The amygdala, in addition to sustained electrophysiological activity, has been shown to be heavily involved in the maintenance of behavioral responsiveness even in the absence of an immediately tangible or visible objective or stimulus (O'Keefe & Bouma, 1969). This includes motivating the organism to engage in the seeking of hidden objects or continuing a certain activity in anticipation of achieving some particular long term goal. At a more immediate level, the amygdala is probably very important in object permanance (i.e. the keeping of an object in mind when it is no longer visible) and concrete or abstract anticipation. Anticipation is, of course, very important in the prolongation of emotional states such as fear or anger, as well as the generation of more complex emotions such as anxiety. In this regard, the amygdala is probably important not only in regard to emotion, but in the maintanance of mood states. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Fear and rage reactions have also been triggered in humans following depth electrode stimulation of the amygdala (Chapman, 1960; Chapman et al., 1954; Heath et al. 1955; Mark et al. 1972). Mark et al. (1972) describe one female patient who following amygdaloid stimulation became irritable and angry, and then enraged. Her lips retracted, there was extreme facial grimmacning, threatening behavior, and then rage and attack--all of which persisted well beyond stimulus termination. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Similarly, Schiff et al. (1982) describe a man who developed intractable aggression following a head injury and damage (determined via depth electrode) to the amygdala (i.e. abnormal electrical activity). Subsequently, he became easily enraged, sexually preoccupied (although sexually hypoactive), and developed hyper-religiosity and psuedo-mystical ideas. Tumors invading the amygdala have been reported to trigger rage attacks (Sweet et al. 1960; Vonderache, 1940). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The amygdals appears capable of not only triggering and steering hypothalamic activity but acting on higher level neocortical processes so that individuals form emotional ideas. Indeed, the amygdala is able to overwhelm the neocortex and the rest of the brain so so that the person not only forms emotional ideas but responds to them, sometimes with vicious, horrifying results. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">DOCILITY & AMYGDALOID DESTRUCTION > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Bilateral destruction of the amygdala usually results in increased tameness, docility, and reduced aggressiveness in cats, monkeys and other animals (Schreiner & Kling, 1956; Weiskrantz, 1956; Vochteloo & Koolhaas, 2007), including purportedly ferocious creatures such as the agoutie and lynxe (Schreiner & Kling, 1956). In man, bilateral amygdala destruction (via neurosurgery) has been reported to reduce and/or eliminate paroxysmal aggressive and violent behavior (Terzian & Ore, 1955). > In some creatures, however, bilateral ablation of the amygdala has been reported to al least initially result in increased aggressive reponding (Bard & Mountcastle, 1948), and if sufficiently aroused or irritated, even the most placid of amygdalectomized animals can be induced to fiercely fight (Fuller et al. 1957). > However, these aggressive responses are very short-lived and appear to be reflexively mediated by the hypothalamus. Hence, these findings (and the data reviewed above) suggests that true aggressive feelings including violent moods, are dependent upon activation of the amygdala. > > SOCIAL-EMOTIONAL AGNOSIA > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Among primates and mammals, bilateral destruction of the amygdala significantly disturbs the ability to determine and identify the motivational and emotional significance of externally occuring events, to discern social-emotional nuances conveyed by others, or to select what behavior is appropriate given a specific social context (Bunnel, 1966; Fuller et al. 1957; Gloor, 1960; Kling & Brothers 1992; Kluver & Bucy, 1939; Lilly et al., 1983; Marlowe et al., 1975; Scott et al., 2010; Terzian & Ore, 1955; Weiskrantz, 1956). Bilateral lesions lower responsiveness to aversive and social stimuli, reduce aggressiveness, fearfullness, competitiveness, dominance, and social interest (Rosvold et al. 1954). This condition is so pervasive that subjects have tremendous diffficulty discerning the meaning or recognizing the significance of even common objects -- a condition sometimes referred to as "psychic blindness", or, the "Kluver-Bucy syndrome" (Lilly et al., 1983; Marlowe et al., 1975; Terzian & Ore, 1955). > Thus, animals with bilateral amygdaloid destruction, although able to see and interact with their environment, may respond in an emotionally blunted manner, and seem unable to recognize what they see, feel, and experience. Things seem stripped of meaning. Like an infant (who similarly is without a fully functional amygdala), individuals with this condition engage in extreme orality and will indiscriminantly pick up various objects and place them in their mouth regardless of its appropriateness. There is a repetitive quality to this behavior, for once they put it down they seem to have forgotten that they had just explored it, and will immediately pick it up and place it again in their mouth as if it were a completely unfamiliar object. > Although ostensibly exploratory, there is thus a failure to learn, to remember, to discern motivational significance, to habituate with repeated contact, or to discriminate between appropriate vs inappropriate stimuli. Rather, when the amygdala has been removed bilaterally the organism reverts to the most basic and primitive modes of object and social-emotional interaction (Brown & Schaffer, 1888; Gloor, 1960; Kluver & Bucy, 1939; Weiskrantz, 1956) such that even the ability to appropriately interact with loved ones is impaired (Lilly et al., 1983; Marlowe et al., 1975; Terzian & Ore, 1955). > For example, Terzian & Ore (1955) described a young man who following bilateral removal of the amygdala subsequently demonstrated an inability to recognize anyone, including close friends, relatives and his mother. He ceased to repond in an emotional manner to his environment and seemed unable to recognize feelings expressed by others. He also demonstrated many features of the Kluver-Bucy syndrome (perserverative oral "exploratory" behavior and psychic blindness), as well as an insatiable appetite. In addition, he became extremely socially unresponsive such that he preferred to sit in isolation, well away from others. > Among primates who have undergone bilateral amygdaloid removal, once they are released from captivity and allowed to return to their social group, a social-emotional agnosia becomes readily apparent as they no longer respond to or seem able to appreciate or understand emotional or social nuances. Indeed, they appear to have little or no interest in social acitivity and persistently attempt to avoid contact with others (Dicks et al. 1969; Jonason & Enloe, 1971; Kling & Brothers 1992; Jonason et al. 1973). If approached they withdraw, and if followed they flee. > Indeed, they behave as if they have no understanding of what is expected of them or what others intend or are attempting to convey, even when the behavior is quite friendly and concerned. Among adults with bilateral lesions, total isolation seems to be preferred. > In addition, they no longer display appropriate social or emotional behaviors, and if kept in captivity will fall in dominance in a group or competitive situation -- even when formerly dominant (Bunnel, 1966; Dicks et al., 1969; Fuller et al., 1957; Jonason & Enloe, 1971; Jonason et al., 1973; Rosvold et al. 1954). > As might be expected, maternal behavior is severly affected. According to Kling (1972), mothers will behave as if their "infant were a strange object be be mouthed, bitten and tossed around as though it were a rubber ball". > EMOTIONAL LANGUAGE & THE AMYGDALA > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Although cries and vocalizations indicative of rage or pleasure have been elicited via hypothalamic stimulation, of all limbic nuclei the amygdala is the most vocally active--particularly the lateral division (Robinson, 1967). In humans and animals a wide range of emotional sounds have been evoked through amygdala activation, such as sounds indicative of pleasure, sadness, happiness, and anger (Robinson, 1967; Ursin & Kaada, 1960). The human amygdala can produce as well as perceive emotional vocalizations (Halgren, 1992; Heit, Smith, & Halgren, 1988). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Conversely, in humans, destruction limited to the amygdala (Freeman & Williams 1952, 1963), the right amygdala in particular, has abolished the ability to sing, convey melodic information or to properly enunciate via vocal inflection. Similar disturbances occur with right hemisphere damage (chapter 10). Indeed, when the right temporal region (including the amygdala) has been grossly damaged or surgically removed, the ability to perceive, process, or even vocally reproduce most aspects of musical and emotional auditory input is significanlty curtailed (Chapter 21). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">AMYGDALA, THE ANTERIOR COMMISSURE, SEXUALITY & EMOTION, > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">When the amygdala or the bed nuclei for the anterior commissure of both cerebral hemispheres are damaged, hyperactivated, or completely inhibited a striking disturbance in sexual and social behavior is evident (Brown & Schaffer, 1888; Gloor, 1960; Kluver & Bucy, 1939; Terzian & Ore, 1955; Schriner & Kling, 1953). Specifically, humans, non-human primates, and felines who have undergone bilateral amygdalectomies will engage in prolonged, repeated, and inappropriate sexual behavior and masturbation including repeated sexual acts with members of different species (e.g. a cat with a dog, a dog with a turtle, etc.). > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">When activated from seizures, patients may involuntarily behave in a sexual manner and even engage in what appears to be intercourse with an imaginary partner. This abnormality is one aspect of a complex of symptoms sometimes referred to as the Kluver-Bucy syndrome. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">As noted, portions of the hypothalamus and amygdala are sexually dimorphic; i.e. there are male and female amygdaloid nuclei (Bubenik & Brown, 1973; Nishizuka & Arai, 1981). In humans the male amygdala is 16% larger (Filipek, et al., 2014), and in male rats the medial amygdala is 65% larger than the female amygdala (Breedlove & Cooke, 2009), and the male amygdala grows or shrinks in the presence of testosterone--findings which may be related to sex differences in sexuality and aggression. Moreover, female amygdala neurons are smaller and more numerous, and densely packed than those of the male (Bubenik & Brown, 1973; Nishizuka & Arai, 1981), and smaller, densely packed neurons fire more easily and frequently than larger ones--which may contribute to the fact that females are more emotional and more easily frightened than males (chapters 7,13,15), as the amygdala is a principle structure involved in evoking feelings of fear (Davis et al., 2010; Gloor, 2010; LeDoux, 2012). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, despite myths to the contrary, females, regardless of species, are more sexually active than males, on average (see chapter 8)--that is, when they are in estrus-- and the human female is capable of experiencing multiple orgasms of increasing intensity--which may also be a function of sex differences in the amygdala. That is, since female primate amygdala neurons are more numerous and packed more closely together (Bubenik & Brown, 1973; Nishizuka & Arai, 1981), and as smaller, tightly packed neurons demonstrate enhanced electrical excitability, lower response thresholds, and increase susceptibility to kindling and thus hyper-excitation, the amygdala therefore is likely largely responsible for sex differences in emotionality and sexuality. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Indeed, electrical stimulation of the medial amygdala results in sex related behavior and activity. In females this includes ovulation, uterine contractions and lactogenetic responses, and in males penile erections (Robinson & Mishkin, 1968; Shealy & Peele, 1957). Moreover, in rats and other animals, kindling induced in the amygdala can trigger estrus and produce prolonged female sexual behavior. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Moreover, the anterior commissure, the band of axonal fibers which interconnects the right and left amygdala/temporal lobe is sexually differentiated. Like the corpus callosum, the anterior commissure is responsible for information transfer as well as inhibition within the limbic system. Specifically, the female anterior commissure is 18% larger than in the male (Allen & Gorski 1992). It has been argued that the increased capacity of the right and left female amygdala to communicate (via the anterior commissure) coupled with the more numerous and more densely packed neurons within the female amygdala (which in turn would decrease firing thresholds and enhance communication), and the sex diffferences in the hypothalamus, would also predispose females to be more emotionally and socially sensitive, perceptive, and expressive (Joseph 2013). Hence, these limbic sex differences induces her to be less aggressive and more compassionate and maternal, and affects her sexuality, feelings of dependency and nurturance, and desire to maintain and form attachments in a manner different than males. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">In contrast, whereas the right and left female amygdala are provided a communication advantage not shared by males, the "male" amygdala in turn may be more greatly influenced by the (medial) hypothalamus via the stria terminalis which is larger in men than women (Allen & Gorski 1992). As noted, the male medial amygdala is larger than its female counterpart (Breedlove & Cooke, 2009) and changes in size in response to testosterone, which is significant as the medial nuclei (and testosterone) is directly implicated in negative and aggressive behaviors (see above). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Although environmental influences can shape and sculpt behavior and the functional organization of the brain (chapter 28), most sex differences are innate and shared by other species (see chapters 7 & 8); a direct consequence of the presence or absence of testosterone during adulthood and fetal development (see Gerall et al. 1992; Joseph 2013, Joseph et al. 1978) and the sexual differentiation of the limbic system. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">THE LIMBIC SYSTEM & TESTOSTERONE > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In large part these and related sex differences in aggressiveness are also a consequence of the relatively higher concentrations of the activating hormone, testosterone flowing through male bodies and brains. The overarching influence of neurological and hormonal predispositions are also indicated by studies which have shown that females who have been prenatally exposed to high levels of masculinizing hormones (i.e. androgens) behave similar to males even in regard to spatial abilities (Joseph et al. 1978; see Gerall et al. 1992). They are also more aggressive and engage in more rough and tumble play as compared to normal females (Money & Ehrhardt, 1972; Ehrhardt & Baker, 1974; Reinisch, 1974) and this is also true of other species such as dogs, wolves, gorillas, baboons, and chimpanzees. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Similarly, female primates and mammals who have been exposed to testosterone during neonatal development display an altered sexual orientation, as well as significantly higher levels of activity, competitiveness, combativeness and belligerence (Mitchell, 1979). Nevertheless, it is important to re-emphasize that it is generally the presence or absence of testosterone during the critical period of neuronal differentiation which determines if one is in possession of a "male" vs "female" limbic system.

> <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">SEXUAL ORIENTATION & HETEROSEXUAL DESIRE > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted, the amygdala surveys the environment searching out stimuli, events, or individuals which are emotionally, sexually or motivationally significant. Moreover, it contains facial recognition neurons which are sensitive to different facial expressions and which are capable of determining the sex of the individual being viewed and which become excited when looking at a male vs female face (Leonard et al. 2005; Rolls 1984). In this regard, the amygdala can act to discern and detect potential sexual partners and then motivate sex-appropriate behavior culminating in sexual intercourse and orgasm. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">That is, an individual who possess a "male" limbic system is likely to view the female face, body and genitalia as sexually arousing because the amygdala and limbic system responds with pleasure when stimulated by these particular features. Conversely, male physical features are likely to excite and sexually stimulate the limbic systems possessed by heterosexual females and homosexual males (Joseph, 2013). This is because, at a very basic level emotional, sexual, and motivational perceptual/behavioral functioning becomes influenced and guided by the anatomical sexual bias of the host. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">OVERVIEW: THE AMYGDALA > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Over the course of early evolutionary development, the hypothalamus reigned supreme in the control and expression of raw and reflexive emotionality, i.e., pleasure, displeasure, aversion, and rage. Largely, however, it has acted as an eye turned inward, monitoring internal homeostasis and concerned with basic needs. With the development of the amygdala, the organism was now equipped with an eye turned outward so that the external emotional features of reality could be tested and ascertained. When signalled by the hypothalamus the amygdala begins to search the sensory array for appropriate emotional-motivational stimuli until what is desired is discovered and attended to. > However, with the differentiation of the amygdala, emotional functioning also became differentiated and highly refined. The amygdala hierarchically wrested control of emotion from the hypothalamus. > The amygdala is primary in regard to the perception and expression of most aspects of emotionality, including fear, aggression, pleasure, happiness, sadness, etc., and in fact assigns emotional or motivational significance to that which is experienced. It can thus induce the organism to act on something seen, felt, heard, or anticipated. The integrity of the amygdala is essential in regard to the anylysis of social-emotional nuances, the organization and mobilization of the persons internal motivational status regarding these cues, as well as the mediation of higher order emotional expression and impluse control. When damaged or functionally compromised, social-emotional functioning becomes grossly disturbed. > The amygdaloid nucleaus via its rich interconnections with other brain regions is able to sample and influence activity occurring in other parts of the cerebrum and add emotional color to ones perceptions. As such it is highly involved in the assimilation and association of divergent emotional, motivational, somesthetic, visceral, auditory, visual, motor, olfactory and gustatory stimuli. Thus it is very concerned with learning, memory, and attention, and can generate reinforcement for certain behaviors. Moreover, via reward or punishment it can promote the encoding, storage and later retrieval of particular types of information. That is, learning often involved reward and it is via the amygdala (in concert with other nuclei) that emotional consequences can be attributed to certain events, actions, or experiences, as well as extracted from the world of possibility so that it can be attended to and remembered. > Lastly, as is evident from studies of individuals with abnormal activity or seizures originating in or involving this nuclei, the amygdala is able to overwhelm the neocortex and thus gain control over behavior. As based on electrophysiological studies, the amygdala seems capable of literally turning off the neocortex (such as occurs during a seizure) at least for brief time periods. That is, the amygdala can induce electrophysiological slow wave theta activity in the neocortex which indicates low levels of arousal (see below) as well as high voltage fast activity. In the normal brain it probably exerts similar influences such that at times individuals (i.e. their neocortex) "lose control" over themselves and respond in a highly emotionally charged manner. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">HIPPOCAMPUS > Memory & Attention > The hippocampus (Ammon's Horn" or the "sea horse") is an elongated structure located within the inferior medial wall of the temporal lobe (posterior to the amygdala) and surrounds, in part, the lateral ventricle. In humans it consists of an anterior and posterior region and depending on the angle at which it is viewed, could be construed as shaped somewhat like an old fashion telephone receiver, or a "sea horse." > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The hippocampus consists of a number of subcomponents, and adjoining structures, such as the parahippocampal gyrus, entorhinal and perirhinal cortex and the uncus (which it shares with the amygdala) are considered by some to be subdivisions, whereas the main body of the hippocampus consists of the dentate gyrus, the subiculum, and sectors referred to as CA1, CA2, CA3, CA4. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The uncus is a bulbar allocortical protrusion located in the anterior-inferior medial part of the temporal lobe, and consists of both the hippocampus and amygdala which become fused in forming this structure. That is the ventral-medial portion of the amygdala becomes fused with the head of the hippocampus, such that the uncus consists of both allocortex and mesocortex--the entorhinal cortex which shrouds the hippocampus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">HIPPOCAMPAL AROUSAL, ATTENTION & INHIBITORY INFLUENCES > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Various authors have assigned the hippocampus a major role in information processing, including memory, new learning, cognitive mapping of the environment, voluntary movement toward a goal, as well as attention, behavioral arousal, and orienting reactions (Douglas, 1967; Eichenbaum et al. 2014; Enbert & Bonhoeffer, 2009; Frisk & Milner, 1990; Grastayan et al., 1959; Green & Arduini, 1954; Isaacson, 1982; Milner, 1966, 1970, 1971; Nishitani, et al., 2009; Olton et al. 1978; Routtenberg, 1968; Squire, 1992; Victor & Agamanolis, 1990; Xu et al., 2012). For example, hippocampal cells greatly alter their activity in response to certain spatial correlates, particularly as an animal moves about in its environment (Nadel, 1991; O'Keefe, 1976; Olton et al., 1978; Wilson & McNaughton, 2013). It also developes slow wave theta activity during arousal (Green & Arduini, 1954) or when presented with noxious or novel stimuli (Adey et al.1960)--at least in non-humans. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, few studies have implicated this nucleus as important in emotional functioning per se, although responses such as "anxiety" or "bewilderment" have been observed when directly electrically stimulated (Kaada et al. 1953). Indeed, in response to persistent and repeated instances of stress and unpleasant emotional arousal, the hippocampus appears to cease to participate in cognitive, emotional, or memory processing (chapter 30). Thus the role of the hippocampus in emotion is quite minimal. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">AROUSAL > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Hippocampal-neocortical interactions. Desynchronization of the cortical EEG is associated with high levels of arousal and information input. As the level of input increases, the greater is the level of cortical arousal (Como et al. 1979; Joseph et al. 1981; Joseph, 2012b, 2009d). However, when arousal levels become too great, efficienty in information processing, memory, new learning, and attention become compromised as the brain becomes overwhelmed (Joseph, 2012b, 2009d; Joseph et al., 1981; Lupien & McEwen, 2010; Sapolsky, 2012). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">When the neocortex becomes desynchronised (indicating cortical arousal), the hippocampus often (but not always) developes slow wave theta activity (Grastyan et al., 1959; Green & Arduni, 1954) such that it appears to be functioning at a much lower level of arousal--as demonstrated in non-humans. Conversely, when cortical arousal is reduced to a low level (indicated by EEG synchrony), the hippocampal EEG often becomes desynchronized. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">These findings suggest when the neocortex is highly stimulated the hippocampus, in order to monitor what is being received and processed, functions at a level much lower in order not to become overwhelmed. When the neocortex is not highly aroused, the hippocampus presumably compensates by increasing its own level of arousal so as to tune in to information that is being processed at a low level of intensity. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Hence, in situations where both the cortex and the hippocampus become desynchronized, there results distractability and hyperresponsiveness such that the subject becomes overwhelmed, confused, and may orient to and approach several stimuli (Grastyan et al., 1959). Attention, learning, and memory functioning are decreased. Situations such as this sometimes also occur when individuals are highly anxious or repetitively emotionally or physically traumatized (see chapter 30). <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The hippocampus consists of 3 layers, layer 2 consisting of pyramidal neurons which provide excitatory output and thus act to activate and arouse target tissues; via the transmitters glutamate and aspartic acid. In addition, the entorhinal cortex provides excitatory input into the hippocampus--input which is derived from the neocortex; using again, aspartic and glutamate acid (reviewed in Gloor, 2010). Specifically, it appears that the hippocampus interacts with the neocortex is regard to arousal via the dorsal medial nucleus of the thalamus, the septal nuclei, the hypothalamus, amygdala and brainstem--structures with which it maintains direct interconnections. As per the neocortex, this sheet of tissue is also innervated by these structures, and by the entorhinal cortex. <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Hence, the hippocampus serves as a major component of an excitatory interface and can be aroused by neocortical activity (via the entorhinal cortex), and can provide excitatory input to directly to subcortical structures and indirectly to the neocortex (via the entorhinal cortex and dorsal medial nucleus). However, if the neocortex becomes excessively aroused, so to might the hippocampus, and vice versa. Under excessively arousing conditions, however, hippocampal pyramidal neurons may become inhibited or even damaged (Lupien & McEwen, 2010; Sapolsky, 2012), thus resulting in loss of memory. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">There is also evidence to suggest that the hippocampus may act so as to reduce extremes in cortical arousal. For example, whereas stimulation of the reticular activating system augments cortical arousal and EEG evoked potentials, hippocampal stimulation reduces or inhibits these potentials such that cortical responsiveness and arousal is dampened (Feldman, 1962; Redding, 1967). On the otherhard, if cortical arousal is at a low level, hippocampal stimulation often results in an augmentation of the cortical evoked potential (Redding, 1967). <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The hippocampus also exerts desynchronizing or synchronizing influences on various thalamic nuclei (e.g., the dorsal medial thalamus) which in turn augments or decreases activity in this region (Green & Adey, 1956; Guillary, 1955; Nauta, 1956, 1958). As the dorsal medial thalamus is the major relay nucleus to the neocortex, the hippocampus therefore appears able to block or enhance information transfer to various neocortical areas (that is, in conjunction with the frontal lobe, see chapter 19). Indeed, it may be acting to insure that certain percepts are stored in memory at the level of the neocortex (Gloor, 2010; Squire 1992) by modulating cortical activity. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is thus likely that the hippocampus may act to influence information reception and storage at the neocortical level as well as possibly reduce extremes in cortical arousal (be they too low or high) perhaps by activating inhibitory circuits in the dorsal medial nucleus, thus ensuring that the neocortex is not over or underwhelmed when engaged in the reception and processing of information. This is an important attribute since very high or very low states of excitation are incompatible with alertness and selective attention as well as the ability to learn and retain information (Joseph et al. 1981; Lupien & McEwen, 2010; Sapolsky, 2012). > > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Aversion & Punishment. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In many ways, the hippocampus appears to act in concert with the medial hypothalamus and septal nuclei (with which it maintains rich interconnections) so as to also prevent extremes in emotional arousal and thus maintain a state of quiet alertness (or quiescence). Moreover, similar to the results following stimulation of the medial hypothalamus, it has been reported that the subjective components of aversive emotion in humans is correlated with electrophysiological alternations in the hippocampus and septal area (Heath, 1976). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The hippocampus also appears to be heavily involved in the modulation of reactions to frustrations or mild punishment (Gray, 1970, 1990), particularly in regard to single trial but not multiple trial learning. For example, the hippocampus responds with trains of slow theta waves when presented with noxious stimuli but habituates or ceases to respond with repeated presentation. It is likely, however, that these physiological responses are secondary to activity within the amygdala and hypothalamus which then effects hippocampal functioning. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">ATTENTION & INHIBITION > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px; vertical-align: baseline;">The hippocampus participates in the elicitation of orienting reactions and the maintainance of an aroused state of attention (Foreman & Stevens, 2007; Grastayan et al., 1959; Green & Arduini, 1954; Nishitani, et al., 2009; Routtenberg, 1968). When exposed to novel stimuli or when engaged in active searching of the environment, hippocampal theta appears (Adey, et al. 1960). However, with repeated presentations of a novel stimulus the hippocampus habituates and theta disappears (Adey et al. 1960). Thus, as information is attended to, recognized, and presumably learned and/or stored in memory, hippocampal participation diminishes. Theta also appears during the early stages of learning as well as when engaged in selective attention and the making of discriminant responses (Grastyan et al. 1959). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px; vertical-align: baseline;">When the hippocampus is damaged or destroyed, animals have great difficulty inhibiting behavioral responsiveness or shifting attention. For example, Clark and Issacson (1965) found that animals with hippocampal lesions could not learn to wait 20 seconds between bar presses if first trained to respond to a continous schedule. There is an inability to switch from a continous to a discontinous pattern, such that a marked degree of perseveration and inability to change sets or inhibit a pattern of behavior once initiated occurs (Douglas, 1967; Ellen, et al. 1964). Habituation is largely abolished and the ability to think or respond divergently is disrupted. Disinhibition due to hippocampal damage can even prevent the learning of a passive avoidance task, such as simple ceasing to move (Kimura, 1958). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px; vertical-align: baseline;">Hence, when coupled with the evidence presented above, it appears that the hippocampus acts to possibly selectively enhance or diminish areas of neural excitation which in turn allows for differential selective attention and differential responding, as well as the storage and consolidation of information into long term memory. When damaged, the ability to shift from one set of perceptions to another, or to change behavioral patterns is disrupted and the organism becomes overwhelmed by a particular mode of input. Learning, memory, as well as attention, are greatly compromised. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px;">LEARNING & MEMORY: THE HIPPOCAMPUS > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">The hippocampus is most usually associated with learning and memory encoding, e.g. long term storage and retrieval of newly learned information (Enbert & Bonhoeffer, 2009; Fedio & Van Buren, 1974; Frisk & Milner, 1990; Milner, 1966; 1970; Nunn et al., 2009; Penfield & Milner, 1958; Rawlins, 2005; Scoville & Milner, 1957; Squire, 1992; Victor & Agamanolis, 1990) particularly the anterior regions. Hence, if the hippocampus has been damaged the ability to convert short term memories into long term memories (i.e. anterograde amnesia), becomes significantly impaired in humans (MacKinnon & Squire, 1989; Nunn et al., 2009; Squire, 1992; Victor & Agamanolis, 1990) as well as primates (Zola-Morgan & Squire, 1984, 2005a, 1986). In humans, memory for words, passages, conversations, and written material is also significantly impacted, particularly with left hippocampal destruction (Frisk & Milner, 1990; Squire, 1992). <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">Bilateral destruction of the anterior hippocampus results in striking and profound disturbances involving memory and new learning (i.e. anterograde amnesia). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Presumably the hippocampus acts to protect memory and the encoding of new information during the storage and consolidation phase via the gating of afferent streams of information and the filtering/exclusion (or dampening) of irrelevant and interfering stimuli. When the hippocampus is damaged there results input overload, the neuroaxis is overwhelmed by neural noise, and the consolidation phase of memory is disrupted such that relevant information is not properly stored or even attented to. Consequently, the ability to form associations (e.g. between stimulus and response) or to alter preexisting schemas (such as occurs during learning) is attenuated. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">THE SEPTAL NUCLEI > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px; vertical-align: baseline;">HIPPOCAMPAL & SEPTAL INTERACTIONS > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px; vertical-align: baseline;">The septal nuclei consists of medial and lateral nuclei, and can be further subdivided into several nuclear components (Ariens Kappers et al., 1936; Swanson & Cowan, 1979), such as the nucleus of the diagonal band of Broca. The septal nuclei is an evolutionary derivative of the hippocampus and the hypothalamus, and in the human brain is richly interconnected with both structures including the amygdala, and the substantia innomminata (SI) which is a major memory center, and which manufactures ACh--a transmitter directly implicated in memory (Gage et al., 1983; Olton, 1990). Andy and Stephan (1968) and Swanson and Cowan (1979) considered the bed nucleus of the stria terminals (which gives rise to a major pathway linking the septal nuclei, and amygdala and hypothalamus) as part of the septal nuclei, whereas others (Gloor, 2010) consider it to be part of the "extended amygdala." Likewise, some consider the nucleus accumbens as part of the septal nuclei, and others consider it part of the "extended amygdala;" i.e. the limbic striatum. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">As noted the septal nuclei is massively interconnected with the hippocampus as well as with the entorhinal cortex (Swanson & Cowan, 1979) via a number of pathways, including the fornix. Directly implicating the septal nuclei in the memory functioning of the hippocampus is the finding that septal activation of this structure results in ACh secretion (Gage et al., 1983), whereas septal grafts into the hippocampus improves learning and memory (Gage et al., 1986). Conversely, lesions of the fimbria-fornix septal-hippocampal pathway results ACh depletion throughout the hippocampus (Gage et al., 1983; Olton, 1990), as well as loss of norepinephrine and serotonin coupled with memory loss (Olton, 1990). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The septal nucleus in part regulate hippocampal memory-related activity not only by stimulating ACh and other neurotransmitter production (Gage et al., 1983, 1986), but as it provides excitatory input and inhibitory-GABAnergic-- especially from the medial septal nuclei which in general exerts inhibitory influences not only on the hippocampus but the amygdala and hypothalamus. In general, it is supposed that the excitatory-inhibitory influences on the hippocampus (like those on the amygdala and hypothalamus) serve to modulate activity and prevent extremes in arousal (Joseph, 1992a, 2012b, 2009d). This is accomplished in part not only through the interconnections maintained with the amygdala, hypothalamus and entorhinal cortex, but the brainstem reticular formation (Petsche et al., 1965)--with which the hippocampus is also connected directly and via the entorhinal cortex. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Septal influences on hippocampal/entorhinal arousal is also indicated by fluctuations in rhythmic slow activity (theta), which is generated by both the hippocampus and entorhinal cortex (Alonso & Garcia-Austt, 2007). As detailed in chapter 14, theta is an indication of hippocampal arousal (Green & Arduini, 1954; Petsche et al., 1965; Vanderwolf, 1992) and is associated with learning and memory (O'Keefe & Nadel, 1978). Theta is a robust electrophysiological phenomenon which has been found in the hippocampus of most species studied, including monkeys (Stewart & Fxx, 1990) and humans (Sano et al., 1970); though in primates it seems to differ from the theta rhythm of non-primates (see Gloor, 2010). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">O'Keefe and Nadel (1978) believe that theta plays an important role in creating the spatial maps that are maintained by hippocampal "place" neurons; i.e. pyramidal neurons which are attuned to specific environmental features and landmarks and the animals place in that environment as they move about. Moreover, long term potentiation (LTP) which is associated with learning and memory, is generated in those neurons demonstrating theta or activity that is at the "theta frequency" (Staubli & Lynch, 2007). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Neurons of the septal nucleus which innervate the hippocampus fluctuate in activity in parallel with changes in the theta rhythm (Petsche et al., 1965), whereas septal lesions abolish hippocampal theta (Green & Arduini, 1954). It has long been believed that septal neurons act as an interface between the reticular formation and the hippocampus (Petsche et al., 1965) and in conjunction with its connections with the amygdala and hypothalamus, therefore modulate hippocampal arousal as well as learning and memory. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">HIPPOCAMPAL & AMYGDALOID INTERACTIONS: MEMORY > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">It has been argued that significant impairments involving short-term memory and motor learning, cannot be produced by lesions supposedly restricted to the hippocampus (Horel, 1978; see also commentary in Eichenbaum et al. 2014); though in fact it is impossible to create such "restricted" lesions. Nevetheless, ignoring for the moment that inconvenient fact, in some instances with supposed restricted lesions, good recall of new information is possible for at least several minutes (Horel, 1978; Penfield & Milner, 1958; Squire 1992). > Moreover, there is considerable evidence which strongly suggests that the hippocampus plays an interdependent role with the amygdala in regard to memory (Gloor 1992, 2010; Halgren 1992; Kesner & Andrus, 1982; Mishkin, 1978; Murray 1992; Sarter & Markowitsch, 2005); particularly in that they are richly interconnected, merge at the uncus, and exert mutual excitatory influences on one another. For example, it appears that the amygdala is responsible for storing the emotional aspects and personal reactions to events in memory, whereas the hippocampus acts to store the cognitive, visual, and contextual variables (chapter 14) whereas that the amygdala activates the hippocampus by providing excitatory input (Gloor, 1955, 2010). > Specifically, the amygdala plays a particularly important role in memory and learning when activities are related to reward and emotional arousal (Gaffan 1992; Gloor 1992, 2010; Halgren 1992; LeDoux 1992, 2012; Kesner 1992; Rolls 1992; Sarter & Markowitsch, 2005). Thus, if some event is associated with positive or negative emotional states it is more likely to be learned and remembered. > The amygdala becomes particularly active when recalling personal and emotional memories (Halgren, 1992; Heath, 1964; Penfield & Perot, 1963), and in response to cognitive and context determined stimuli regardless of their specific emotional qualities (Halgren, 1992). However, once these emotional memories are formed, it sometimes requires the specific emotional or associated visual context to trigger their recall (Rolls, 1992; Halgren, 1992). If those cues are not provided or ceased to be available, the original memory may not be triggered and may appear to be forgotten or repressed. However, even emotional context can trigger memory (see also Halgren, 1992) in the absence of specific cognitive cues. > Similarly, it is also possible for emotional and non-emotional memories to be activated in the absence of active search and retrieval, and thus without hippocampal or frontal lobe participation. Recognition memory which may be triggered by contextual or emotional cues. Indeed, there are a small group of neurons in the amygdala, as well as a larger group in the inferior temporal lobe which are involved in recognition memory (Murray, 1992; Rolls, 1992). Because of amygdaloid sensitivity to visual and emotional cues, even long forgotten memories may be evoked via recognition, even when search and retrieval repeatedly fail to activate the relevant memory store. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">According to Gloor (1992), "a perceptual experience similar to a previous one can through activation of the isocortical population involved in the original experience recreate the entire matrix which corresponds to it and call forth the memory of the original event and an appropriate affective response through the activation of amygdaloid neurons." This can occur "at a relatively non-cognitive (affective) level, and thus lead to full or partial recall of the original perceptual message associated with the appropriate affect." > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In this regard, it appears that the amygdala is responsible for emotional memory formation whereas the hippocampus is concerned with storing verbal-visual-spatial and contextual details in memory. Thus, in rats and primates damage to the hippocampus can impair retention of context, and contextual fear conditioning, but it has no effect on the retention of the fear itself or the fear reaction to the original cue (Kim & Fanselow 1992; Phillips & LeDoux 1992, 2012; Rudy & Morledge 2014). In these instances, fear-memory is retained due to preservation of the amygdala. However, when both the amygdala and hippocampus are damaged, striking and profound disturbances in memory functioning result (Kesner & Andrus, 1982; Mishkin, 1978). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Therefore, the role of the amygdala in memory and learning seems to involve activities related to reward, orientation, and attention, as well as emotional arousal and social-emotional recognition (Gloor, 1992, 2010; Rolls, 1992; Sarter & Markowitsch, 2005). If some event is associated with positive or negative emotional states it is more likely to be learned and remembered. That is, reward increases the probability of attention being paid to a particular stimulus or consequence as a function of its association with reinforcement (Gaffan 1992; Douglas, 1967; Kesner & Andrus, 1982). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, the amygdala appears to reinforce and maintain hippocampal activity via the identification of motivationally significant information and the generation of pleasurable rewards (through action on the lateral hypothalamus). However, the amygdala and hippocampus act differentially in regard to the effects of positive vs. negative reinforcement on learning and memory, particularly when highly stressed or repetitively aroused in a negative fashion. For example, whereas the hippocampus produces theta in response to noxious stimuli the amygdala increases its activity following the reception of a reward (Norton, 1970). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">TEMPORAL LOBES & LATERALITY. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">It is now very well known that lesions involving the mesial-inferior temporal lobes (i.e. destruction or damage to the amygdala/hippocampus) of the left cerebral hemisphere typically produce significant disturbances involving verbal memory--particularly as constrasted with individuals with right sided destruction. Left sided damage disrupts the ability to recall simple sentences, complex verbal narrative passages, or to learn verbal paired-associates or a series of digits (Frisk & Milner 1990; Milner, 1966, 1970, 1971; Squire 1992). > In contract, right temporal destruction typically produces deficits involving visual memory, such as the learning and recall of geometic patterns, visual or tactile mazes, locations, objects, emotional sounds, or human faces (Corkin, 1965; Milner, 1965; Nunn et al., 2009; Kimura, 1963). Right sided damage also disrupts the ability to recognize (via recall) olfactory stimuli (Rausch et al. 1977), or recall emotional passages or personal memories (Cimino et al., 1991; Wechsler, 1973). > > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">It appears, therefore, that the left amygdala and hippocampus are highly involved in processing and/or attending to verbal information, whereas the right amygdala/hippocampus is more involved in the learning, memory and recollection of non-verbal, visual-spatial, environmental, emotional, motivational, tactile, olfactory, and facial information. These issues and the differing roles of these nuclei in memory formation, as well as amnesia and repression will be discussed in greater detail in chapters 29, 30. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">THE PRIMARY PROCESS > AMYGDALA & PLEASURE > The amygdala maintains a functionally interdependent relationship with the hypothalamus in regard to emotional, sexual, autonomic, consumatory and motivational concerns. It is able to modulate and even control rudimentary emotional forces governed by the hypothalamic nucleus. However, the amygdala also acts at the behest of hypothalamically induced drives. For example, if certain nutritional requirements need to be meet, the hypothalamus signals the amygdala which then surveys the external environment for something good to eat (Joseph, 1982, 1992a). On the other hard, if the amygdala via environmental surveillance were to discover a potentially threatening stimulus, it acts to excite and drive the hypothalamus as well as the basal ganglia so that the organism is mobilized to take appropriate action. > When the hypothalamus is activated by the amygdala, instead of responding in an on/off manner, cellular activity continues for an appreciably longer time period (Dreifuss et. al., 1968). The amygdala can tap into the reservoir of emotional energy mediated by the hypothalamus so that certain ends may be attained (Joseph, 1982, 1992a) > AMYGDALA & HIPPOCAMPAL INTERACTIONS DURING INFANCY > HALLUCINATIONS > The amygdal-hippocampal complex, particularly that of the right hemisphere, is very important in the production and recollection of non-linguistic and verbal-emotional images associated with past experience. In fact direct electrical stimulation of the temporal lobes, hippocampus and particularly the amygdala (Gloor, 1990, 2010) not only results in the recollection of images, but in the creation of fully formed visual and auditory hallucinations (Gloor 1992, 2010; Halgren 1992; Halgren et al., 1978; Horowitz et al., 1968; Malh et al., 1964; Penfield & Perot, 1963), as well as feelings of familiarity (e.g. deja vus). > Indeed, it has long been know that tumors invading specific regions of the brain can trigger the formation of hallucinations which range from the simple (flashing lights) to the complex. The most complex forms of hallucination, however, are associated with tumors within the most anterior portion of the temporal lobe (Critchley, 1939; Gibbs, 1951; Gloor 1992, 2010; Halgren 1992; Horowitz et al. 1968; Tarachow, 1941); i.e. the region containing the amygdala and anterior hippocampus. > Similarly, electrical stimulation of the anterior lateral temporal cortical surface results in visual hallucinations of people, objects, faces, and various sounds (Gloor 1992, 2010; Halgren 1992; Horowitz et al., 1968)--particularly the right temporal lobe (Halgren et al. 1978). Depth electrode stimulation and thus direct activation of the amygdala and/or hippocampus is especially effective. > For example, stimulation of the right amygdala produces complex visual hallucinations, body sensations, deja vu, illusions, as well as gustatory and alimentary experiences (Weingarten et al. 1977), whereas Freeman and Williams (1963) have reported that the surgical removal of the right amygdala in one patient abolished hallucinations. Stimulation of the right hippocampus has also been associated with the production of memory- and dream-like hallucinations (Halgren et al. 1978; Horowitz et al. 1968). > The amygdala also becomes activated in response to bizarre stimuli (Halgren, 1992). Conversely, if activated to an abnormal degree, it may in turn produce bizarre memories and abnormal perceptual experiences. In fact, the amygdala contributes in large part to the production of very sexual as well as bizarre, unusual and fearful memories and mental phenomenon including dissociative states, feelings of depersonalization, and hallucinogenic and dream-like recollections (Bear, 1979; Gloor, 1986, 1992, 2010; Horowitz et al. 1968; Mesulam, 1981; Penfield & Perot, 1963; Weingarten et al. 1977; Williams, 1956). In addition, sexual feelings and related activity and behavior are often evoked by amygdala stimulation and temporal lobe seizures (Halgren, 1992; Jacome, et al. 1980; Gloor, 1986, 2010; Remillard, et al. 1983; Robinson & Mishkin, 1968; Shealy & Peele, 1957), including memories of sexual intercourse (Gloor 1990) or severe emotional trauma and abuse (Gloor, 2010). > Moreover, intense activation of the temporal lobe and amygdala has been reported to give rise to a host of sexual, religious and spiritual experiences; and chronic hyperstimulation (i.e. seizure activity) can induce some individuals to become hyper-religious or visualize and experience ghosts, demons, angels, and even God, as well as claim demonic and angelic possession or the sensation of having left their body. > > LSD. > As is well known, LSD can elicit profound hallucinations involving all spheres of experience. Following the administration of LSD high amplitude slow waves (theta) and bursts of paroxysmal spike discharges occurs in the hippocampus and amygdala (Chapman & Walter, 1965; Chapman et al. 1963), but with little cortical abnormal activity. In both humans and chimps, when the temporal lobes, amygdala and hippocampus are removed, LSD ceased to produce hallucinatory phenomena (Baldwin et al. 1959; Serafintides, 1965). Moreover, LSD induced hallucinations are significantly reduced when the right vs. left temporal lobe has been surgically ablated (Serafintides, 1965). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px; vertical-align: baseline;">Overall, it appears that the amygdala, hippocampus, and the neocortex of the temporal lobe are highly interactionally involved in the production of hallucinatory experiences. Presumably, it is the neocortex of the temporal lobe which acts to interpret this material (Penfield & Perot, 1963) as perceptual phenomena. Indeed, it is the interrelated activity of the temporal lobes, hippocampus and amygdala which not only produce memories and hallucinations, but dreams. In fact, the amygdalas involvement in all aspects of emotion and sexual functioning, including associated memories, the production of overwhelming fear as well as bizarre and dream-like mental phenomenon, may well account for why this type of unusual stimuli, including personal and innocuous memories also appears in dreams. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 15px;">DREAMING > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">When hallucinations follow depth electrode or cortical stimulation, much of the material experienced is very dream-like (Gloor 1990, 1992; Halgren et al., 1978; Malh et al., 1964; Penfield & Perot 1963) and consists of recent perceptions, ideas, feelings, and other emotions which are similarly illusionary and dream-like. Indeed, the right amygdala, hippocampus, and the right hemisphere in general (Broughton, 1982; Goldstein et al., 1972; Hodoba, 1986; Humphrey & Zangwill, 1961; Kerr & Foulkes, 1978; Meyer et al. 2007) also appear to be involved in the production of deam imagery as well as REM sleep (chapter 10). For example stimulation of the amygdala triggers and increases ponto-geniculo-occipital paradoxical activity during sleep (Calvo, et al. 2007), which in turn is associated with REM and dreaming. In addition, during REM, the hippocampus begins to produce slow wave, theta activity (Jouvet, 1967; Olmstead, Best, & Mays, 1973; Robinson et al. 1977), which is associated with long-term potentiation which is associated with learning and memory (see chapter 14). Presumably, during REM, the hippocampus and amygdala act as a reservoir from which various images, emotions, words, and ideas are drawn and incorporated into the matrix of dream-like activity being woven by the right hemisphere. It is probably just as likely that the right hippocampus and amygdala serve as a source from which material is drawn during the course of a daydream. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The Right Hemisphere & Dreams. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">There have been reports of patients with right cerebral damage, hypoplasia and abnormalities in the corpus callosum who have ceased dreaming altogether, suffer a loss of hypnogic imagery or tend to dream only in words (Botez et al. 2005; Humphrey & Zangwill, 1951; Kerr & Foulkes, 1981; Murri et al. 1984). However, there have also been some report that when the left hemisphere has been damaged, particularly the posterior portions (i.e. aphasic patients), the ability to verbally report and recall dreams also is greatly attenuated (e.g., Murri et al. 1984). Of course, aphasics have difficulty describing much of anything, let alone their dreams. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Electrophysiologically the right hemisphere also becomes highly active during REM, whereas, conversely, the left brain becomes more active during N-REM (Goldstein et al. 1972; Hodoba, 1986). Similarly, measurements of cerebral blood flow have shown an increase in the right temporal regions during REM sleep and in subjects who upon wakening report visual, hypnagogic, hallucinatory and auditory dreaming (Meyer et al. 2007). Interestingly, abnormal and enhanced activity in the right temporal and temporal-occipital area acts to increase dreaming and REM sleep for an atypically long time period (Hodoba, 1986). Hence, it appears that there is a specific complementary relationship between REM sleep and right temporal electrophysiological activity. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Interestingly, daydreams appear to follow the same 90-120 minute cycle that characterize the fluctuation between REM and NREM periods, as well as fluctuations in mental capabilities associated with the right and left hemisphere (Broughton, 1982; Kripke & Sonneschein 1973). That is, the cerebral hemisphere tend to oscillate in activity every 90-120 minutes -- a cycle which appears to correspond to the REM-NREM cycle and the appearance of day and night dreams. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Forgotten Dreams. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Most individuals, however, have difficulty recalling their dreams. This may seem paradoxical considering that hippocampal theta is being produced. However, this is theta punctuated by high levels of desychronized activity, which is not conducive to learning. In this regard, theta activity may represent the reverberating activity of neural circuits formed during the day, such that the residue of day time memories come to be inserted into the dream. Conversely, due to the high level of desychronization occuring in the hippocampus (as it is so highly aroused), although it contributes images and the days memories, it does not participate in storing these dream-like experiences into memory. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Consider the results from temporal lobe, amygdala, and hippocampal electrical stimulation on memory recall and the production of hallucinations. Although personal memories are often activated at low intensities of stimulation (memories which are verified not only by the patient but family), if stimulation is sufficiently intense, the memory instead will become dreamlike and populated by hallucinated and cartoon like characters (Halgren, et al. 1978). That is, at low levels of stimulation memories are triggered but these memories become increasingly dream-like with high levels of activity. Moreover, once these high levels of stimulation are terminated, patients soon become verbally amnesic and fail to verbally recall having had these experiences (Gloor, 1992; Horowitz, et al. 1968). However, these memories can be later recalled if subjects are provided with specific contextual cues (Horowitz, et al. 1968). The same can occur during the course of the day when a fragment of a conversation, or some other experience, suddenly triggers the recall of a dream from the previous night which had otherwise been completely forgotten. Presumably it had seemingly been forgotten because the hippocampus did not participate in their storage and thus could not assist in their retrieval (see chapters 29, 20). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">There is also some evidence to suggest that different regions of the hippocampus show different levels of arousal during paradoxical sleep. For example, it appears that the posterior hippocampus becomes activated during paradoxical sleep and shows theta activity, whereas the more anterior portions become inhibited (Olmstead et al. 1973). As the anterior portions are more involved in new learning (at least in humans), whereas the posterior hippocampus is more concerned with old and well established memories, this would suggest that the posterior hippocampus is contributing older or already established memories to the content of the dream--which explains why theta, which is associated with learning and memory, is also produced during the dream--that is, it is replaying various fragmentary memories. Conversely, the inhibition of the anterior region would prevent this dream material from becoming re-memorized. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">DREAMS & INFANCY > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In the newborn, and up until approximately 6-9 months, there are two distinct stages of sleep which correspond to REM and N-REM periods demonstrated by adults (Berg & Berg, 1978; Dreyfus-Brisac & Monod, 1975; Parmelee et al. 1967). Among infants, however, REM occur during wakefulness as well as during sleep. In fact, REM can be observed when the eyes are open, when the infant is crying, fussing, eating, or sucking (Emde & Metcalf, 1970). Moreover, REM is also observed to occur within a few moments after an infant begins to engage in nutritional sucking and appears identical to that which occurs during sleep (Emde & Metcalf, 1970). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The production of REM during waking in some respects seems paradoxical. Nevertheless, it might be safe to assume that like an adult, when the infant is in REM, he or she is dreaming, or at least, in a dream-like state. Possibly, this state corresponds to what Freud has described as the Primary Process. That is, when produced when the infant is crying or fussing, it is dreaming of whatever relief it seeks. Correspondingly, REM which occurs while eating or sucking may have to do with the limbic structures which are involved not only in the production of dream-like activity, but the identification, learning and retention of motivationally significant information (i.e. the amygdala and hippocampus). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Presumably this relationship is a consequence of REM as well as eating and sucking being mediated, in part, by the amygdala as well as other limbic nuclei, which are also concerned with forming motivationally significant memories. Hence, when hungry, the hypothalamus becomes aroused which activates the amygdala which is responsible for the performing environmental surveillance so as to attend, orient to, identify and approach motivationally significant stimuli and eat. However, because the infants brain is so immature and as its resources for meeting its limbic needs are quite rudimentary, under certain conditions prolonged hypothalamus induced amygdala activation results in the formation and recall of relevant memories which may be experienced as hallucinations of the desired object. That is, previously formed neural networks become activated and the infant begins to dream and hallucinate food and will then suck and smack its lips as if eating or sucking when it is awake, in REM, and there is no food present. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">THE PRIMARY PROCESS > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The hypothalamus, our exceedingly ancient and primitive Id, has an eye that only sees inward. It can tell if the body needs nourishment but cannot determine what might be good to eat. It can feel thirst, but has no way of slacking this desire. The hypothalamus can only say: "I want", "I need", and can only signal pleasure and displeasure. However, being the seat of pleasure, the hypothalamus can be exceedingly gracious in rewarding the organism when its needs are met. Conversely, when its needs go unmet it can respond not only with displeasure and feelings of aversion, but with undirected fury and rage. It can cause the organism to cry out. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Nevertheless, the cry does not produce the immediately desire relief or reduction in tension. There is thus a pressure on the limbic system and the organism to engage in environmental surveillance so as to meet the needs monitored by the hypothalamus. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Over the course of the first months of life, as the amygdala and then hippocampus develop, the organism begins to develop an eye that not only sees outward, but which can register and recall events, objects, people, etc., associated with tension reduction, pleasure and the satiaty of the infants internal needs (e.g. the taste, smell, feeling of mother's breast and milk, the experience of sucking and relief, etc.). This is called learning. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif;">With the maturation of these two limbic nuclei the infant is increasingly able to differentiate what occurs in the external environment based on hypothalamically monitored needs and the emotional/motivational significance of that which is experienced. The infant can now orient, selectively attend, determine what brings satisfaction, and store this information in memory. > > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">PRIMARY IMAGERY > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Although admittedly we have no direct knowledge as to the psychic interactions in the neonate, it does seem reasonable to assume that as the neocortex and underlying structures and fiber pathways mature, neural "prgroams" are formed which correspond to the repeated registration of experiences which are deemed significant (e.g. pleasurable). That is, neural pathways which are repetitively fired, deactivated or activated in response to specific sensory and affective activities and experiences, become associated with that activity, such that an associated neural circuit is formed (chapter 14); i.e. a memory is created. Eventually, if this circuit is reactivated, the "learned" pattern is reexperienced; i.e. the organism remembers. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Thus, infants as young as 2 days of age can learn to suck at the mere sight of a bottle (see Piaget, 1954) and in order to receive milk as a reinforcement, infants can even modify their sucking response (Sameroff & Cameron, 1979). Hence, they are susceptible to classical conditioning (Sameroff & Cavanagh, 1979), although the possibility of operant conditioning has not been established. Nevertheless, the fact that they can recognize the bottle and suck (as well as cry and shed tears) indicates that various regions of the limbic system, especially that of the amygdala is functional and that learning and the creation of specific, context specific neural circuits have been formed very early in life. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Thus, when the amygdala/hippocampus are stimulated by a hungry hypothalamus, the events and images associated with past experiences of pleasure can not only be searched out externally, but recalled in imaginal form. For example, as an infant experiences hunger and stomach contractions as well as it own cries of displeasure, these states become associated with the sound, smell, taste, etc. of mother and her associated movement and other stimuli which accompany being fed (cf Piaget, 1952, pp. 37, 407-408). Repetitively experienced, the sequence from hunger to satiety evokes and becomes associated with the activation of certain neural pathways and the creation of a specific neural network subserving that memory (chapter 14). > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Eventually, when the infant becomes hungry, if prolonged there is the possibility that the entire neural sequence associated with hunger and feeding (i.e. hunger, mother, food, satiaty), may become involuntarily triggered and activated (via association) such that an "image" of being fed is experienced. The activation of these rudimentary and infantile memory-images is probably what consititutes, at least in part, the primary process. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Behaviorally this is manifested by REM and via sucking and tongue movements as if eating, when in fact there is no food present (cf, Piaget, 1952). That is, when hungry, the infant will begin to cry, rapid eye movement (REM) might be observed, and then the infant will stop crying and smack its lips and make sucking movement (mediated by the amygdala) as if it were being fed. The infant experiences the experience of being fed in the form of a dream (Joseph, 1982) or hallucination, although it is awake. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In that the brain of the human infant is quite immature for in fact several years, which in turn restricts information reception and processing (chapters 23-28), and given the limited amount of reality contact infants are able to achieve, these rudimentary memories and images (even when occurring during waking, i.e. REM), are probably indistinguishable from actual experience simply because they are experience. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Like a dream, when replayed, the infant presumalby reexperiences to some degree the sensations, emotions, etc., originally linked to tension reduction. Thus, the young infant, as yet unable to distinguish between representation and reality, responds to the image as reality (Freud, 1900, 1911), even while awake--as manifested by REM. When hunger is prolonged the association linked to feeding are triggered and for a brief time period the infant behaves as if its hunger has been sated. Reality is replaced by an image, or rather, a "dream". This is the primary process. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Since the hypothalamus (which monitors internal homeostasis) is not conscious that the dream images experienced are not real, it initially accepts the memory/dream images transmitted from the amygdala and hippocampus and ceases to cry, i.e. it responds to the imagined sources of nourishment just as it responds to a cue-tone associated with a food reward (Nakamuar & Ono, 1986; Ono et al., 1980). However, the hypothalamus is not long fooled, for the primary process does not offer effective long lasting relief from tension. As the pain of hunger remains and increases, limbic activity is increased, and the image falls away to be replaced by a cry of hunger (Joseph, 1982). The amygdala and hippocampus are thus forced to renew their surveillance of the environment in search of sources of tension reduction. Cognitive development is thus promoted. > <span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">"Whatever was thought of (desired) was simply imagined in an hallucinatory form, as still happens today with our dream-thoughts every night. This attempt at satisfaction by means of hallucination was abandoned only in consequence of the absence of the expected gratification, because of the disappointment experienced. Instead, the mental apparatus had to decide to form a conception of the real circumstances in the outer world and to exert itself to alter them...The increased significance of external reality heightened the significance also of the sense-organs directed towards the outer word, and of the consciousness attached to them; the later now learned to comprehend the qualities of sense in addition to the qualities of pleasure and "pain" which hitherto had alone been of interest to it. A special function was instituted which had periodically to search the outer word in order that its data might be already familiar if an urgent need should arise; this function was attention. Its activity meets the sense-impressions halfway, instead of awaiting their appearance. At the same time there was probably introduced a system of notation, whose task was to deposit the results of this periodical activity of consciousness--a part of that which we call memory" (Freud, 1911, pp. 410-411). > ==============================================================================================

=
================================================= Social Emotional Development and Infant Speech
 * LIMBIC LANGUAGE **

Hypothalamus, Amygdala, Septal Nuclei, Cingulate

** R. Gabriel Joseph, Ph.D. **

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">LIMBIC LANGUAGE <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Human language, and the original impetus to vocalize, springs forth from roots buried within the depths of the ancient limbic lobes which is buried in the body of the brain. These vocalizing structures include the hypothalamus, amygdala, cingulate gyrus (Joseph, 1982, 2012a, 1993, 2014, 1999e; Jurgens, 2011, 2012, 2014; MacLean, 2011; Ploog, 2012; Robinson, 1967, 1972) as well as brainstem structures such as the periaqueductal grey. It is these ancient vocal-emotional centers which explain why non-human animals also vocalize to convey feeling and emotion. Thus, although non-humans and infants generally do not have the capacity to meaningfully communicate in grammatical word sequences, they still vocalize, and these vocalizations are often limbic and emotional in origin (Hauser, 1997; Joseph, 1982, 2012a; Jurgens, 2011; Jurgens and Muller-Preuss, 1977; MacLean, 2011; Meyer et al., 1973; Ploog, 2012; Robinson, 1967, 1972). We know that language is evoked from the limbic system and not from the neocortical surface of the brain, since electrode stimulation of the neocortex does not provoke vocalization. Although the neocortex can segment, grammatically organized, and sequence the sounds of language, the source of speech belongs to the old limbic brain. Indeed, emotional cries and warning calls have been produced via stimulation of wide areas of the limbic system (Jurgens, 2011, 2012; Jurgens et al. 1982; Jurgens and Muller-Preuss, 1977; MacLean, 2011; Ploog, 2012; Robinson, 1967, 1972) including the human amygdala (Halgren, 2012; Heith, Smith and Halgren, 1988) and the anterior cingulate gyrus (Meyer et al., 1973) which also becomes activated when speaking (Frith and Dolan, 1997; Passingham, 1997; Paulesu et al., 1997; Peterson et al., 1988). And these and other limbic structures often become activated in response to certain emotional sounds. In fact, the limbic system is more vocal than any other part of the brain (Jurgens, 2011; Robinson, 1967).

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Characteristically, limbic vocalizations are evoked in situations involving sexual arousal, terror, anger, rage and extreme fear and fright and are similarly expressed by a wide range of species. They are also expressed by infants such as when separated from the primary caretaker when young. Some of these limbic vocalizations begin to be emitted soon after birth.

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In fact, because these vocalizations are mediated by the limbic system, human infants and apes and monkeys reared in isolation or (in the case of non-human primates) with surgically muted mothers and thus with little or no "language" experience or training, are able to produce complex and appropriate emotional calls and cries which accurately indicate fear or distress. They are also expressed by children born blind and deaf. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In the case of non-human primates, they will react appropriately to these vocalizations the first time they are exposed to them (Herzog and Hopf, 1984; Winter et al., 1973). For example, squirrel monkeys reared in isolation respond appropriately with fear and anxiety in response to warning "yapping" calls (signifying the presence of a predator) the very first time they are heard (Herzog and Hopf, 1984). They will also produce an appropriate "yapping" cry when they are first exposed to a potential predator. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The first vocalizations of human infants (McGraw, 1969; Milner, 1967; Piaget, 1952; Spitz and Wolf, 1946; Sroufe, 1996), including anencephalics (Lemire et al., 1978; Monnier, 1956) and those born deaf and blind (Eibl-Eisbesfeldt, 1995) are similarly emotional in origin and limbically mediated (Joseph, 1982, 2012a, 1999b,e). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Initially these sounds consist of grunts and sounds indicative of displeasure, and weeks then months later will include pleasure, fear and the separation cry. These vocalizations can also be produced by direct stimulation of the hypothalamus, amygdala, or anterior cingulate gyrus (Jurgens, 2011, 2012, 2014; MacLean, 2011; Meyer et al., 1973; Ploog, 2012; Robinson, 1967, 1972). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The human amygdala (Halgren, 2012; Heith et al., 1988) and anterior cingulate (Frith and Dolan, 1997; Passingham, 1997; Paulesu et al., 1997; Peterson et al., 1988) become activated when hearing or producing emotional words and sounds, whereas the medial hypothalamus (MacLean, 2011; Robinson, 1967, 1972) and the midbrain periaqueductal grey (Casey et al., 2014; Coghill et al., 2014; Zhang et al., 2014) become active when experiencing or vocally expressing negative mood states. Hence the term: "limbic language" (Joseph, 1982; Jurgens, 2011).

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The normal pattern of maturational development, as is evident behaviorally and as based on myelination and metabolic activity, is that the brainstem and cerebellum begin to develop in advance of the forebrain, which in turn matures in a upward, rostral and paramedial to lateral arc, i.e. diencephalon (medial hypothalamus), limbic system (amygdala), striatum, cingulate, neocortex (Barkovich et al., 1988; Brody et al., 1987; Gibson, 1991; Harbord, et al., 2011; Holland, et al., 1986; Lee et al., 1986). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Because the maturation of the forebrain and neocortex are exceedingly prolonged (Benes, 2014; Blinkov and Glezer, 1968; Brody, Kinney, Kloman, and Gilles, 1987; Conel, 1939, 1941; Debakan, 2000; Flechsig, 1901; Holcomb et al., 2012; Huttenlocher, 2011; Paus et al., 1999; Pfefferbaum, et al., 2014; Reiss, et al., 1996; Yakovlev and Lecours, 1967), and as the limbic system matures in advance of the neocortical speech areas, infants (and their mothers) are dependent on limbic language and the limbic system in order to communicate their needs and to discern the social-emotional intentions of others. This is why infants will react appropriately even if the speaker speaks a "foreign language" (Fernald, 1993). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Since these emotional sounds are limbically produced and comprehended, and because these structures are common to all humans and mammals, these sounds are stereotypically vocalized and comprehended cross-culturally, and by infants and different animal species (Beier and Zautra, 1972; Fernald, 2012; Fernald et al., 1989; Hauser, 1997; Joseph, 1988a, 1993; Kramer, 1964; Nakazima, 1975). Hence, the famous aside: "I don't know what they are saying, but I sure don't like the sound of it!" <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, be it human, primate, or social mammal, certain sounds arouse or convey fear, sadness, caution or alarm (e.g. thunder, growling, low tones), or conversely, pleasure, gaiety, or peaceful conditions (e.g., soft or higher rolling, and smoother pitched tones and melodies). It is because certain sounds can signify and arouse specific and universal mood states that movie and television programs are often accompanied by "mood" music. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted, despite neocortical immaturity, and although lacking denotative, grammatical language skills, infants are quite adept at distinguishing between different emotional vocalizations so as to determine the mood state and intentions of others (Fernald, 1993; Haviland and Lelwica, 1987). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, it has been demonstrated that preverbal infants between the ages of 10 weeks and 5 months are capable of appropriately discerning, discriminating and responding to social-emotional vocalizations conveying approval, disproval, happiness, and anger (Fernald, 1993; Haviland and Lelwica, 1987). Moreover, 5 month old (American) infants are able to make these discriminations even in the absence of words and vocabulary, and in response to nonsense English, as well as to German and Italian vocalizations (Fernald, 1993). However, infants even younger are capable of producing these same limbic vocalizations (Joseph, 1982), and the same is true of those born deaf and blind, which again indicates that these abilities are innate. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">OVERVIEW: LIMBIC LANGUAGE DEVELOPMENT <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Be it infant H. sapiens sapiens, or non-human primates and mammals (hereafter referred to as "primates" and "mammals"), different structures within the limbic system produce different (as well as similar) vocalizations. The type of cry or vocalization elicited, in general, depends upon which limbic structure has been activated (Jurgens, 2011; Jurgens and Muller-Preuss, 1977; Robinson, 1967, 1972). This is because different limbic structures, and in fact, different divisions within these nuclei, subserve unique functions, and maintain different anatomical interconnections with various regions of the brain (chapter 13). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, portions of the septal nuclei, hippocampus, anterior cingulate, medial amygdala, and medial hypothalamus have been repeatedly shown to generate negative and unpleasant mood states (MacLean, 2011; Olds and Forbes, 1981; Robinson, 1967, 1972). Other limbic tissues, including the lateral hypothalamus, lateral amygdala and portions of the septal nuclei, are associated with pleasurable feelings (chapter 13). Hence, areas associated with pleasurable sensations often give rise, when sufficiently stimulated, to pleasurable calls, whereas those linked to negative mood states, will trigger shrieks and cries of alarm. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, because these limbic structures mature at somewhat different, albeit overlapping rates (Benes, 2014; Brody et al., 1987; Debakan, 2000; Holcomb et al., 2012; Paus et al., 1999; Pfefferbaum, et al., 2014; Reiss, et al., 1996; Yakovlev and Lecours, 1967) the infant's emotional vocal repertoire also develops in a stereotypical fashion in parallel. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, the midbrain periaqueductal gray and hypothalamus are almost fully functional at birth, and as will be detailed, these structures can produce crying, screaming, and grunting sounds--vocalizations characteristic of the human infant. It is the somewhat later to mature amygdala and cingulate gyrus which in turn are responsible for the increasing complexity and range of the infant's vocal-emotional repertoire, including the development of early and late babbling (Joseph 1982, 2012a, 1993). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Initially infant emotional sound production appears to convey generalized meanings, e.g. pleasure, displeasure. These sounds are associated with the hypothalamus and periaqueductal gray. Over the following weeks and months, these vocalizations become modified and more elaborate and produced in specific contexts, and are then increasingly shaped and tied to specific mood states or events and social-emotional phenomenon (Joseph, 1982, 2012a, 1999c; Milner, 1966; Piaget, 1952). That is, the increasing range of sounds produced and perceived become modulated, differentiated, more elaborate and complex, and specifically tied to sadness, joy, affection, sorrow, fear, and so on, rather than just pleasure and displeasure. These increases in vocal complexity in turn are associated with maturational events occurring within the amygdala and anterior cingulate. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Similar developmental alterations and elaborations in limbic vocalizations have been noted among primates. For example, vervet monkeys employ three distinct calls which they differentially produce in the presence of eagles, snakes and leopards (Cheney and Seyfarth, 2011). Experienced and normally reared monkeys respond to these calls by looking up ("eagle"), looking down ("snake"), or climbing up a tree ("Leopard") depending on which call is produced, even when played from a tape recorder (Seyfarth et al. 1980). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, infants reared in isolation merely respond with generalized alarm when presented with these same calls, and are as likely to look up as down as climb a tree. That is, although they recognize the emotional significance of the call, they are not yet able to differentiate these sounds as signifying particular and specific social-emotional events or situations. These abilities are increasingly acquired over the course of the first few months as the limbic system matures, and in response to specific environmental experiences. In fact, these differential limbic maturational and vocalization events are also associated with and parallel social-emotional developmental behavioral changes which are mediated by these same limbic structures (Joseph, 2012a, 1999c). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">LIMBIC LANGUAGE HIERARCHICAL DEVELOPMENT <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The brain develops and matures in a caudal to rostral and paramedial to lateral arc such that functions associated with the midbrain periaqueductal gray are soon followed by that of the medial hypothalamus which sits atop and is partly contiguous with the midbrain (detailed in chapters 23 and 24). At birth, the medial hypothalamus appears to be functionally active and/or at a state of semi-functional and anatomical maturity. An advanced state of (neonatal) hypothalamic maturity is indicated by the emergence of associated behaviors and vocalizations (Joseph, 2012a, 1993, 1999c), myelination patterns (e.g., Debakan, 2000; Gibson, 1991; Langworthy, 1937; Yakovlev and Lecours, 1967), and the establishment of its massive fiber interconnections with the midbrain and periaqueductal gray (Gilles et al., 2003; Debakan, 2000; Langworthy, 1937; Yakovlev and Lecours, 1967). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted the neonatal and infant neocortex is exceedingly immature and in the case of the neonate, displays almost no functional activity (Blinkov and Glezer, 1968; Chugani, 2014; Conel, 1939, 1941; Debakan, 2000; Flechsig, 1901; Holcomb et al., 2012; Huttenlocher, 2011; Paus et al., 1999; Pfefferbaum, et al., 2014; Reiss, et al., 1996; Yakovlev and Lecours, 1967). Hence, the behavior of the human neonate appears to be mediated by the brainstem and midbrain periaqueductal gray which mediate chewing, sucking, swallowing, phonating, and breathing, and reflexively vocalizes when aroused (Joseph, 1999c; Jurgens, 2012, 2014; Ploog, 2012), as well as the medial hypothalamus which appears to be functionally active at birth. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">This explains why similar neonatal sounds can be vocalized by anencephalics who are generally devoid of neural tissue anterior to the diencephalon (Emde, Gaensbauer, and Harmon, 1976; Lemire et al., 1978; Monnier, 1956). With complete forebrain destruction, and following depth electrode activation of the brainstem periaqueductal gray (Jurgens, 2014; Larson et al., 2014; Zhang et al., 2014), or with stimulation of the hypothalamus (MacLean, 2011; Robinson, 1967, 1972) grunting, howling and crying can be reflexively triggered, including those similar to those produced by a howling infant or anencephalic. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Brainstem vocalization centers appear to be fully functional at birth, though they also continue to mature and myelinate over the course of the first 3-12 postnatal months (Debakan, 2000; Gilles, 1991; Yakovlev and Lecours, 1967), whereas the neocortex, including the neocortical speech areas can take well over 10 years to reach an advanced stage of maturation. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, when the hypothalamus is stimulated, not just emotional vocalizations but complex and emotionally congruent behaviors can be elicited including facial displays of rage or pleasure. On the other hand, as with midbrain stimulation, once the stimulation is terminated, the behavior and vocalizations cease. Nevertheless, although the hypothalamus responds in an on/off fashion, so long as it is activated (such as by hunger or pain) and in the case of neonates (because it is so immature) it will continue to react and cry out for long time periods, even in the absence of an obvious external stimulating source. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">By contrast, activation of the more highly evolved amygdala and anterior cingulate produces complex and sustained feeling and mood states even after the stimulation is removed (see chapter 13). Moreover, cingulate stimulation can produce emotional sounds that accurately reflect or which have no relation to the individual's mood. These latter structures, however, begin to functionally mature at a later age of development, which is why associated behaviors and emotions appear at later ages as well (Joseph, 1999b,c,). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, the later maturation of the amygdala is associated with the developing of cooing and other emotional sounds and the onset of "early babbling" (Joseph, 1982, 2012a, 1999b). "Early babbling," although not emotional per se, appears to be a function of the the amygdala's massive fiber pathway to the masticatory centers in the brainstem, which, at this age, are decidedly immature (see Takeuchi et al., 1988). That is, because of its immaturity, it induces rudimentary and repetitive reflexive jaw and lip movements including chewing, sucking, and swallowing--functions that many scientists believe are integral to speech development (Weiss, 1951; for related discussion see Moore and Ruark, 1996). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The much later to develop "late" (canonical) babbling, and other complex emotional vocalizations, are associated with the maturation of the anterior cingulate (Joseph, 1993, 1999b)--a structure which when electrically stimulated produces all manner of complex and repetitive sounds including "dadadada" (Dimmer and Luders, 1995; Penfield and Welch, 1951). The cingulate ("canonical") late babbling stage is followed by jargon babbling and then human speech, beginning with the first words, all of which are associated with increased neocortical maturity and the establishment of neocortical hierarchical control over limbic and brainstem nuclei. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Thus, babbling and limbic language and emotional speech become increasingly complex as the hypothalamus, followed by the amygdala and cingulate gyrus mature--structures which myelinate and functionally develop following the myelination of the brainstem. Moreover, not just speech, but associated limbic behaviors also emerge in parallel. Again, the normal pattern of maturational development is that the brainstem develops in advance of the forebrain, which in turn matures in a caudal to rostral and paramedial to lateral arc, i.e. diencephalon (medial hypothalamus), limbic system (amygdala), striatum, cingulate, neocortex (Barkovich et al., 1988; Brody et al., 1987; Gibson, 1991; Harbord, et al., 2011; Holland, et al., 1986; Lee et al., 1986). Again, however, these neocortical maturational events continue well into late childhood, adolescence and adulthood (e.g., Pfefferebaum, et al., 2014; Jernigan, et al., 1991; Kinney et al., 1988). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">With the later maturation of the neocortical speech areas, it appears that limbic language becomes hierarchically and sequentially reorganized, thereby giving rise, in children and adults, to segmented-prosodic, temporal sequential, grammatical, vocabulary-rich human speech (Joseph, 1982, 2012a, 1999a,e; for related discussion see Hallet and Proctor 1996; Herschkowitz, Kagan, and Zilles, 1997).

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In this regard, a hierarchy of progressive complexity in emotional vocalization and feeling states could be said to begin with the periaqueductal gray and medial hypothalamus, and then progressively expands so as to incorporate the amygdala followed by the cingulate gyrus and finally the neocortical speech areas which hierarchically mediate and sequence limbic emotional vocalizations thereby producing complex, vocabulary-rich grammatical speech (Joseph, 1999a,e; 2000a). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, with the maturation (and evolution) not only of the neocortical speech areas but the inferior parietal lobule, Broca's and Wernicke's areas become interlocked at the neocortical level thereby giving rise to the language axis, and modern human speech through the hierarchical representation of limbic speech which is punctuated and fractionated into words and temporal sequences (Joseph, 1982, 1999e, 2000a). However, even in the adult, these neocortical tissues remain dependent on the limbic system and the brainstem in order to vocalize and communicate as these tissues are directly connected. If these pathways are destroyed the patient may become mute. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Therefore, because the maturation of the limbic forebrain and neocortex is exceedingly prolonged (Benes, 2014; Blinkov and Glezer, 1968; Brody et al., 1987; Conel, 1939, 1941; Debakan, 2000; Flechsig, 1901; Holcomb et al., 2012; Huttenlocher, 2011; Paus et al., 1999; Pfefferbaum, et al., 2014; Reiss, et al., 1996; Yakovlev and Lecours, 1967) so too is the development and acquisition of human language, the first sounds of which appear to be reflexively uttered by the brainstem periaqueductal gray and the medial hypothalamus. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">PERIAQUEDUCTAL GRAY AND VOCALIZATION <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Activity within the midbrain periaqueductal gray (which receives extensive input from the amygdala, hypothalamus, and other limbic nuclei) can trigger the production of a variety of sounds that are suggestive of exceedingly negative feelings (Larson et al. 2014; Zhang et al. 2014). The periaqueductal gray, in fact, becomes functionally active in response to noxious and painful stimuli as do other pontine-midbrain nuclei as demonstrated through functional imaging (Casey et al., 2014; Coghill et al., 2014). However, if the periaqueductal gray is disconnected from the limbic system and neocortex (such as by a midbrain transection), stimulation of this nuclei will continue to evoke vocalization. Nevertheless, with the exception of facial contortions (produced by the fifth and 7th cranial nerves) and changes in breathing and thus vocalization, stimulation of the isolated periaqueductal gray is not accompanied by complex behavioral displays, and when the stimulation is removed, the vocalizations immediately cease. Moreover, patients with "bulbar palsy" (due to partial brainstem injury and disconnection), report that their vocalizations do not correspond to their actual feelings. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">This suggests that periaqueductal gray sound production, that is, at the level of the midbrain, is due to the activation of pre-programmed motor engrams that are stored within the brainstem. Moreover, this suggests that the periaqueductal gray responds reflexively in response to painful stimuli (such as when an individual cries "ouch"), and in reaction to emotional impulses transmitted via the amygdala and hypothalamus -nuclei with which it is intimately interconnected. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, if denied forebrain input, or if provided abnormal input, although the periaqueductal gray may vocalize, the "emotions" conveyed may not have a corresponding feeling state but instead represents a reflexive motor program involving the vocalization centers. In fact, the coordinated activity of these tissues and activation of these motor programs would enable an individual to laugh, cry, or howl, even if the brain anterior to the midbrain were dead and there was no evidence of consciousness. Hence, similar vocalizations are produced by anencephalics born with only a brainstem (Emde et al., 1976; Lemire et al., 1978; Monnier, 1956). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, the midbrain periaqueductal gray receives input from throughout the brainstem, spinal cord, as well as the hypothlamus, amygdala, cingulate, and the speech areas in the left and right frontal lobes, and is able to activate and coordinates the laryngeal, oral-facial, and principal and accessory muscles of respiration and inspiration thereby producing a wide range of vocalizations (Jurgens, 2011, 2012, 2014; Larson et al. 2014; Zhang et al. 2014). The periaqueductal gray appears to be the site where particular vocalization motor patterns are stored. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">When the periaqueductal gray is activated by impulses received from the limbic system or neocortex, it activates the appropriate motor program and then organizes and coordinates the oral-laryngeal and respiratory muscles so that the appropriate sounds can be produced (Jurgens, 2014; Zhang et al, 2014). In this manner the felt aspects of emotion (as generated within the forebrain) are accompanied by appropriate sound production as released and mediated by the brainstem and cranial nerves (see chapter 17). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">THE MEDIAL HYPOTHALAMUS: CRYING AND SCREAMING <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">By birth the hypothalamus has established massive fiber interconnections with the midbrain and periaqueductal gray (Gilles et al. 2003; Debakan, 2000; Langworthy, 1937; Yakovlev and Lecours, 1967) and is thus capable of reflexively activating this structure. That is, the infantile periaqueductal gray reflexively vocalizes in response to hypothalamic influences and thus may cry in reaction to hunger or thirst. As detailed in chapter 13, the hypothalamus is involved in all aspects of endocrine, hormonal, visceral and autonomic nervous system functioning and contains lipostatic, glucose, and osmoreceptors which are sensitive to the body's fat content and fluctuations in circulating metabolities and water levels. The hypothalamus also becomes exceedingly active when hungry and while eating or simply looking at food (Nakamura and Ono, 1986; Rolls, Burton, and Mora, 1976). Thus, the monitoring of internal homeostasis is a major function of the hypothalamus (see chapter 13). As the remainder of the forebrain is exceedingly immature, the vocalizing behavior and auditory capabilities of the neonate appear to reflect brainstem-periaqueductal and medial hypothalamic influences, such that the neonate will grunt and cry in response to hunger, thirst, pain. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted, for the first several weeks of life, the infant displays only two behavioral states suggestive of emotion: Quiescence and displeasure --demonstrated by crying, screaming, or inactivity. Among its many functions the medial hypothalamus is also associated with quiescence, the parasympathetic nervous system, and the experience and expression of extreme distress and negative mood states (Olds and Forbes, 1981) including the production of extremely negative vocalizations (MacLean, 2011; Robinson, 1967, 1972). Depth electrode activation of the medial hypothalamus is so aversive subjects will work to reduce it (Olds and Forbes, 1981). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">From the perspective of the maturing brain, for the first several days after birth, the infant is little more than a hypothalamus, a brainstem, and a very immature autonomic nervous system. These structures exert reflexive behavioral control over the infant which responds reflexively to bodily needs.

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">As the remainder of the forebrain is exceedingly immature, quiescence and distress, the two predominate behavioral states demonstrated by the infant (McGraw, 1969; Milner, 1967; Piaget, 1952; Spitz and Wolff, 1946), appear to be associated with medial hypothalamic activity which can act directly on the periaqueductal gray. Thus, for example, when experiencing hunger or thirst, the infantile hypothalamus may activate the brainstem including the periaqueductal gray which reflexively reacts by crying. However, once sated, the medial hypothalamus becomes quiescent. THE LATERAL HYPOTHALAMUS AND THE PLEASURE PRINCIPLE The medial hypothalamus begins to mature before the lateral nucleus--a developmental process which may not be complete until late puberty (Yakovlev and Lecours, 1967). However, as the lateral hypothalamus (and other forebrain nuclei) mature, it increasingly exerts its own unique influences and the developing infant will increasingly demonstrate and vocalize feelings of pleasure (Joseph, 2012a; see also Hershkowitz et al. 1997). Lateral hypothalamic functional maturation, however, also overlaps with that of other forebrain structures, including the amygdala. And, feelings and vocalizations indicative of pleasure have been triggered following excitation of a number of diverse limbic areas including the amygdala, cingulate gyrus, and the medial forebrain bundle (Jurgens, 2011; Jurgens and Muller-Preuss, 1977; Olds and Forbes, 1981; Robinson, 1967, 1972). Following depth-electrode placement, animals will repeatedly engage in self-stimulatory activity to deliver electric impulses to these nuclei. However, the greatest area of concentration of reward sites, and the highest rates of self-stimulatory activity occur in the lateral hypothalamus. According to Olds (1956), animals "would contine to stimulate as rapidly as possible until physical fatigue forced them to slow or to sleep." By contrast, if the lateral region is destroyed the experience of pleasure and emotional responsiveness is almost completely attenuated (Marshall and Teitelbaum, 1974). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">Thus, whereas the medial hypothalamus produces distress and quiescence, the later to mature lateral hypothalamus produces feelings of pleasure, such that by 3 months of age, infants will smile and vocalize with genuine pleasure (Sroufe, 1996). In this regard, it could be said that the hypothalamus mediates the pleasure principle (Joseph, 2012a). In fact, activation of the lateral hypothalamus produces vocalizations suggestive of extreme pleasure, and in humans can even trigger uncontrolled laughter (Davison and Kelman, 1939; Ironside, 1956; Martin, 1950. Hence, as the lateral hypothalamus (and other forebrain structures mature) infants also begin to laugh around 3-4 months of age. Presumably the hypothalamus activates the periaqueductal gray and brainstem respiratory centers (e.g. Boliek, Hixon, Watson, and Morgan, 1996) which reflexively produces facial expressions and respiration-related vocalizations suggestive of pleasure, including laughter, or conversely, cries of distress. However, by 3 months of age the amygdala is also significantly contributing to the infant's behavior and speech patterns. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">Nevertheless, as forebrain maturity continues in a medial to lateral and a caudal to rostral arc, initially the hypothalamus matures at an earlier age than the amygdala (and forebrain), and exerts a more profound influence on neonatal behavior. Over the ensuing weeks, and as the lateral and medial hypothalamus mature, followed by the amygdala/forebrain, the vocal as well as emotional and behavioral repertoire of the infant expands (Joseph, 1982, 2012a), whereas crying begins to wane due to increased cortical inhibitory control (Hershkowitz et al. 1997). By 3-4 months of age infants will smile with genuine pleasure and produce laughter similar to adult laughter (Sroufe, 1996); a function of increasingy forebrain maturity (e.g. Hallett and Proctor, 1996; Herschkowitz et al., 1997). As the amygdala and the forebrain mature, the infant's ability to vocalize becomes increasingly differentiated and expressive of more complex emotions such as joy, wariness and fear. THE AMYGDALA, HYPOTHALAMUS, AND PERIAQUEDUCTAL GRAY The amygdala responds to and in turn, exerts inhibitory and excitatory influences on the brainstem and hypothalamus and thus emotional behavior, through the amygdalofugal fiber pathway and stria terminalis (Davis et al. 1997; Joseph, 2012a; Rosen and Schulkin, 1998). The stria terminalis and amygdalofugal pathways are bidirectional and interlink the medial and lateral amygdala with the medial and lateral hypothalamus and the periaqueductal gray (Krettek and Price, 1978). Through these same pathways the amygdala can activate the brainstem including the periaqueductal gray, and is able to modulate and even control rudimentary emotional forces governed by the hypothalamus as well as act at the behest of hypothalamically induced drives. For example, if certain nutritional requirements need to be meet, the hypothalamus signals the amygdala via the stria terminalis. The amygdala then surveys the external environment in search of an appropriate stimulus. On the other hand, if presented with a potentially threatening or motivationally significant stimulus, the amygdala may stimulate hypothalamic activity (as well as the brainstem and striatum, e.g. Davis et al. 1997; LeDoux, 1996; Rosen and Schulkin, 1998) so that the organism is mobilized to take appropriate action. Hence, when the hypothalamus is activated and driven by the amygdala, instead of responding in an on/off manner which is typical of the hypothalamus, cellular activity continues for an appreciably longer time period (Dreifuss, Murphy, and Gloor, 1968; Rolls 2012). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">The amygdala also acts independently of the hypothalamus, and can, for example, generate extreme feelings of pleasure and corresponding facial expressions and vocalizations (chapter 13). Indeed, the lateral amygdala receives and contributes fibers to the medial forebrain bundle which in turn has its site of origin in the lateral hypothalamus (Mehler, 1980) and projects to the brainstem. Moreover, the amygdala is rich in cells containing enkephalins, and opiate receptors can be found throughout this nucleus (Atweh and Kuhar, 1977; Uhl, Kuhar, and Snyder, 1978). It is also a major pleasure center which promotes self-stimulatory activity (Olds and Forbes, 1981) and the vocalization of pleasure (e.g. cooing and gooing). Therefore, as the medial and then the lateral amygdala mature and gains hierarchical control over the hypothalamus and brainstem, the emotional repertoire expands as does the infant's ability to perceive and produce a variety of exceedingly complex social-emotional behaviors and vocalizations, including, as will be detailed later, the development of "early babbling." THE AMYGDALA AND SOCIAL-EMOTIONAL VOCALIZATION Although there is much debate as to the infant's emotional capabilities, or lack thereof (e.g. Hershkowitz et al. 1997; Izard, 1991; Sroufe, 1996), for the first several weeks of postnatal life the limbic forebrain is simply too immature to accurately perceive or vocalize emotional feelings other than displeasure. Likewise, although the newborn and week-old infant will lift the corners of its mouth, as if "smiling," these initial "smiles" do not appear to represent true emotions (Spitz, Emde, and Metcalf, 2000; Sroufe, 1996; Wolff, 1963) but are probably brainstem reflexes (Joseph, 1999c). It is only as the lateral hypothalamus, and medial and lateral amygdala (and other forebrain structures) begin to mature that the infant becomes capable of truly "smiling," laughing, and producing complex social-emotional vocalizations (for related discussion see Boliek et al. 1996; Hallet and Proctor, 1996; Herschkowitz et al. 1997; Nobre and Plunkett 1997). The amygdala is an exceedingly complex structure consisting of a variety of nuclei including the claustrum and the limbic and corpus striatum (Heimer and Alheid, 1991; MacLean, 2011; Mogenson and Yang, 1991). It also maintains massive interconnections with the hypothalamus, cingulate, frontal and parietal lobes, and periaqueductal gray (Amaral, Price, Pitkanen, and Thomas, 2012; Krettek and Price, 1978; Mesulam and Mufson, 1982; O'Keefe and Bouma, 1969). In addition, the amygdala receives direct input from the auditory areas in the temporal lobe via a thick neural pathway, the inferior arcuate fasciculus, and through the claustrum which is a "broken off" segment of the amygdala situated near and is connected with the auditory receiving areas in the temporal lobe. Hence the human amygdala responds to complex auditory-affective stimuli including words and sentences (Halgren, 2012; Heit et al., 1988), and if electrically stimulated, patients report hearing voices which tend to be experienced as emotionally significant (Gloor, Olivier, and Quesney, 1981). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">The medial amygdala (in conjunction with the hippocampus) forms a cortical bulbous protrusion in the anterior-medial temporal lobe (the uncus), and over the course of evolution gave rise to sheets of 3-layered allocortex, then 5-layered mesocortex, and finally neocortex and contributed to the formation of the auditory neocortex and Wernicke's area, which are thus, in part, evolutionary extensions of the amygdala. As noted, immediately beneath the insula and approaching the auditory neocortex is a thick band of amygdala-cortex, the claustrum. Over the course of evolution the claustrum apparently split off from the amygdala due to the expansion of the temporal lobe and the passage of additional axons coursing throughout the white matter (Gilles et al., 2003) including the arcuate fasciculus. Nevertheless, the claustrum maintains rich interconnections with the auditory cortex as well as the amygdala (Gilles et al., 2003) which in turn is linked directly with the neocortical auditory areas. This is evident from dissection of the human brain which reveals that the fibers of the arcuate fasciculus (and claustrum) project to and from the amygdala, leading not only to Wernicke's area, but continuing through the inferior parietal lobule, projecting directly to Broca's area.



<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">Hence, via these extensive interconnections with the auditory neocortex (and the midbrain inferior-auditory colliculus and medial geniculate of the thalamus) the amygdala is able to receive and analyze auditory input in order to discern and identify stimuli which are emotionally and motivationally significant (Gloor, 1997; Halgren, 2012). When emotional, sexual and motivationally relevant stimuli (e.g. food, sex partner) are detected the amygdala can organize appropriate behavioral and vocal responses and can trigger startle or defensive reactions, as in response to transient sounds, or those typically made by predators, prey, or potential mates (Edeline and Weinberger, 1991; Hitchock and Davis, 1991; Gloor, 1960, 1986, 1997; Hocherhman and Yirmiya, 2011; Rolls, 2012; Ursin and Kaada, 1960). These motor-behavioral reactions, in turn, are mediated by the limbic and corpus striatum, the periaqueductal gray, and lower brainstem, all at the behest of the amygdala. Moreover, it can vocalize via the neocortical speech areas and pariaqueductal gray. In fact, in conjunction with the anterior cingulate the amygdala is one of the most vocally responsive structures of the brain (Jurgens, 2011, 2012; Robinson, 1967, 1972) and become activated in response to emotional sounds and words (Halgren, 2012; Heit et al., 1988). In humans, destruction limited to the normal amygdala, the right amygdala in particular, can severely disrupt the ability to sing, convey melodic information or to enunciate properly via vocal inflection, and can result in great changes in pitch and the timbre of speech (Freeman and Williams, 1952, 1963; Joseph, 2012a). With bilateral destruction of the normal (vs the diseased) amygdala, emotional speech production and the capacity to respond appropriately to emotionally significant visual or auditory stimuli is significantly disrupted (Lilly, Cummings, Benson, and Frankel, 2003; LeDoux, 1996; Marlowe, Mancall, Thomas,1975; Scott et al., 1997; Terzian and Ore, 1955). The amygdala, therefore is primary in regard to the perception and expression of social and emotional nuances and in large part is responsible for the expression and comprehension of not just limbic language, but human speech, the sounds of which are shunted to and from the amygdala via the inferior fasciculus and the claustrum which is a "broken off" segment of the amygdala situated near the primary auditory receiving areas. As noted (and described briefly below), portions of the auditory neocortex -which extends from the anterior and medial temporal lobe and beyond the insula to include the superior temporal lobe and the inferior parietal lobule- is in part, an evolutionary derivative of the amygdala. In this regard it could be argued that the primary, secondary and auditory association areas including Wernicke's area, have evolved (at least in part) from the amygdala, and in fact remain extensively interconnected with this nuclei via the inferior portions of the arcuate fasciculus as well as the claustrum. In consequence, when the neocortical auditory areas are injured, the amygdala is sometimes disconnected and can no longer extract or inpart emotional nuances to incoming or outgoing sounds. For example, with right superior temporal lobe lesions, patients may suffer from a receptive auditory affective agnosia, as well as an agnosia for environmental sounds (see chapter 10). They may have difficulty ascertaining the feelings of others or perceiving social emotional nuances. Hence, emotional peception and expression may become grossly disorganized and inappropriate. By contrast, if the left amygdala is disconnected from the left superior temporal lobe, patients may verbally complain that they consciously feel cut off from their emotions (chapter 10). Moreover, with left temporal lobe dysfunction, speech and thought processes may come to be abnormally invested or devoid of emotion, and patients may be diagnosed as psychotic and/or paranoid. Hence, although the left and right amygdala are functionally lateralized, with the right amygdala significantly larger than the left, both contribute significantly to the perception and expression of language, and assist in maintaining the functional integrity of the neocortical auditory areas in the right and left temporal lobe. It is through these interconnections that limbic languages comes to be hierarchically organized at the level of the temporal neocortex. BEHAVIORAL INDICES OF AMYGDALA MATURATION The amygdala is the most emotional and socially responsive structure of the brain (Davis, Walker, and Lee, 1997; Gloor, 1997; Halgren, 2012; Kling and Brothers 2012; LeDoux 1996; Rolls 2012; Rosen and Schulkin, 1998) and appears responsible for the ability to experience and covey complex emotions including love and guilt, and to form intense emotional (and sexual) attachments (Joseph, 2012a, 1999b). Nevertheless, at birth and over the course of the ensuing several weeks, the amygdala is so immature that its contributions appear to be rather negligible, which is which is why, for example, infants remain fearless until after 6 months of age. Fear is a primary emotion associated with the amygdala (Chapman, 1960; Davis et al. 1997; Gloor, 1997; Halgren, 2012; Rosen and Schulkin, 1998; Ursin and Kaada, 1960). However, as based on behavioral-emotional indices, it also appears that neurons within the immature amygdala (and overlying temporal lobe), i.e. those which are responsive to the faces and eyes (Hasselmo, Rolls, and Baylis, 1989; Morris, Frith, Perett, Rowland, Young, Calder, and Colan, 1996; Kawashima et al., 1999; Rolls, 1984), may well be responsible for the newborn's tendency to briefly attend to facelike stimuli (Carpenter, 1974; Goren, Sarty, and Wu, 1975). In fact, in conjunction with the overlying (partly contiguous) temporal lobe, the amygdala contains neurons which selectively respond to smiles, to the eyes, the direction of gaze, and which differentiate between male and female faces and the emotions they convey (Hasselmo et al. 1989; Kawashima, et al., 1999; Morris et al. 1996; Rolls, 1984). For example, the normal human amygdala will respond to frightened faces by altering and increasing its activity (Morris et al. 1996). Moreover, the left amygdala acts to discriminate the direction of another person's gaze, whereas the right amygdala becomes activated while making eye-to-eye contact (Kawashima, et al., 1999). Again, however, initially the amygdala is so immature that its influences are nearly negligible. Indeed, the amygdala (uncus) does not reach advanced levels of myelination until around the end of the first postnatal year (Yakovlev and Lecours, 1967). However, as the amygdala and its auditory and facial-featuring detecting neurons develop, and around 2-months of age, the infant increasingly recognizes and orients toward familiar faces, and by 6-months it can discriminate between male and female faces. By 9 months it can easily discriminate between different facial expressions (Caron, Caron and Myers, 1985; Carpenter, 1974; Sroufe, 1996)--functions associated with the temporal lobe and amygdala. As these structures and their facial-feature-detecting neurons mature, infants increasingly attend to and demonstrate an almost irresistible interest in facial stimuli (Bronson, 1972). If presented with a strange face, although the infant may look away, it will also quickly look back, "and will make eye-to-eye contact as though drawn by a magnet" (Sroufe, 1996, p. 103). Moreover, these facial-detecting-neurons are richly interconnected with amygdala-temporal lobe neurons concerned with social emotional functioning, including those which trigger smiling, laughter, and even a crying, sobbing, and a fear response (e.g., Chen and Forster, 1973; Offen et al., 1976; Sethi and Rao, 1976). Therefore, activation of these tissues can also trigger eye-to-eye facial contact, smiling, social behavior, as well as a variety of social-emotional vocalizations. The localization of these functions to the amygdala is exceedingly adaptive, as the face as well as the voice serve as major sources of information. When simultaneously employed these dual input/output channels promote social communication and thus language, and provide amygdala neurons and neural pathways with growth promoting stimulation (Joseph, 1999b). Face-to-face interaction provokes and reinforces the tendency to vocalize, and provides added meaning to what is heard and said, and also contributes to the formation of emotional attachments and the seeking of social contact and stimulation. Therefore, as the amygdala increasingly attends to the human face, emotional vocalizations become more complex, and, around 3-4 months of age (in conjunction with increased forebrain control), smiling and crying become less reflexive, cooing increases in frequency, and the ability to produce a "social" smile becomes more pronounced (e.g. Hershkowitz et al. 1997). The infant becomes increasingly social, and coos and smiles during greeting, and when making face-to-face and eye-to-eye contact, especially with their mothers (Ainsworth, 1973; D'Odorico, 1984; Sroufe, 1996; Wolff, 1969). Likewise, between the ages of 3 weeks to 4 months infants become increasingly capable of appropriately discerning, discriminating and responding to social-emotional vocalizations conveying approval, disproval, happiness, and anger (Fernald, 1993; Haviland and Lelwica, 1987). Infants are able to make these discriminations based merely on the perception of emotional prosody, in the absence of words and vocabulary, and in response to non-sense English, as well as to German and Italian vocalizations (Fernald, 1993). THE AMYGDALA, FEAR, AND ATTACHMENT As noted, medial forebrain structures begin to mature before lateral nuclei. Thus the medial hypothalamus begins to mature before the lateral nuclei, and the medial amygdala before the lateral amygdala. Thus, whereas the medial amygdala becomes increasingly well myelinated around 3-4 months (Yakovlev and Lecours, 1967), the functional maturation of the lateral amygdala is much more prolonged. It is the lateral amygdala which mediates the fear response (Chapman, 1960; Davis et al. 1997; Gloor, 1997; Halgren, 2012; Rosen and Schulkin, 1998; Ursin and Kaada, 1960); an emotion which, in conjunction with the development of "working memory" (Hershkowitz et al., 1997) and the maturation of the hippocampus, septal nuclei and cingulate, exerts significant influences on the development of attachment and fear of strangers (Joseph, 2012, 1998b, 1999b). As the amygdala does not approach advanced levels of myelination until around 8-12 months of age, the infant remains basically fearless for the first 8 months of postnatal development. This is exceedingly adaptive. If fear were to emerge at an earlier age, the infant might withdraw from those who normally provide it with loving social-emotional stimulation. It is only as the medial and lateral amygdala reach an advanced stage of myelination and development that the fear response and related vocalizations emerge (Joseph, 2012a), that is, around the 8-12 months (Emde et al. 1976; Sroufe and Waters, 1976). Infants, therefore, become increasingly wary and fearful of strangers--emotions evoked by the amygdala. Therefore, if strangers approach, the child may look away or Cover their eyes. Or the child will try to get away. Fear is the most common emotional reaction elicited from amygdala stimulation in human and non-humans (Chapman, 1960; Davis et al. 1997; Gloor, 2012, 1997; Halgren, 2012; Rosen and Schulkin, 1998; Ursin and Kaada, 1960). Likewise, the human amygdala becomes activated when experiencing fear (Halgren, 2012; Rauch et al., 1996). Abnormal activity in the amygdala or the overlying temporal lobe can in fact evoke overwhelming, terrifying feelings of death-like "nightmarish" fear (Herman and Chambria, 1980; Strauss, Risser, and Jones, 1982). Hence, the fear response and the expression of fearful vocalizations, which appears around 8-12 months of age, are obvious indications of, and are correlated with, the later stages of amygdala maturation, a structure which also significantly contributes to the formation of specific social-emotional attachments (Joseph, 2012a, 1999b). Indeed, because the infant experiences fear, the fear response directly contributes to the formation of specific attachments and the avoidance of those who are unfamiliar. Although the amygdala is associated with the fear response, this structure also promotes social contact seeking. Therefore, as noted, destruction of the amygdala abolishes social behavior, and animals and humans will actively avoid social contact. In the infant, however, social contact seeking is basically indiscriminate due to the immaturity of this structure and the paucity of counterbalancing influences normally exerted by the septal nucleus and cingulate gyrus on the amygdala and these tendendencies (Joseph, 2012a, 1999b). Thus, as the amygdala matures (and since the septal nuclei and cingulate do not begin to mature until later in development), until the infant is 6-7 months of age it will smile at the approach of anyone, even complete strangers. The child will also vigorously protest any form of separation from strangers (e.g. if they leave the room). This stage corresponds to the amygdaloid maturational period where septal and cingulate influences are still less well developed. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">In fact, so intense is the need for physical and social contact that young animals raised in social isolation will form attachments to bare wire frames (Harlow, 1962), to television sets, to dogs that might maul them, to creatures that might kill them (Cairn, 1966) and among humans, to mothers that might abuse them. In fact, among humans, so pervasive is this need for physical interaction and social stimulation that when grossly reduced or denied, the result is often death. For example, in several well known studies of children raised in foundling homes during the early 1900's when the need for contact was not well recongized, morbidity rates for children less than 1 year of age was over 70%. Of 10,272 children admitted to the Dublin Foundling home during a single 25 year period, only 45 survived (Langmeier and Matejcek, 1975). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">However, as the septal nuclei and anterior cingulate begin to mature the infant becomes more discriminant in their interactions and around seven months of age a very real and specific attachment if formed; for example, to one's mother --an attachment which becomes progressively more intense and stable. This period represents septal and cingulate developmental influences such that global contact seeking becomes increasingly narrowed and restricted; attachment and avoidance behaviors which are reinforced by the generation of the fear response. Therefore, by 9 months, 70% of children respond aversively, whereas by 12 months 90% respond aversively and will cry out and vocalize and display anxiety, fear and even flight reactions if the stranger were to approach (Schaffer, 1966; Spitz and Wolf, 1946; Waters et al. 1975). SEPTAL SOCIAL BEHAVIOR As detailed in chapter 22, the septal nuclei does not begin to differentiate or mature until receiving axonal projections from the amygdala and extended amygdala (Brown, 2003; Humphrey, 1967), and does not begin to reach advanced stages of development until around after 3 years of age (Yakovlev and Lecours, 1967). Phylogenetically the septal nuclei appears to be a derivative of the hypothalamus and hippocampus, and contributed to the evolution of the medial portions of the hemispheres (Sanides 1964) including portions of the cingulate gyrus. It also increases in relative size and complexity as we ascend the ancestral tree, attaining its greatest degree of development in humans. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">Specifically, the septal nuclei lies in the medial portions of the hemispheres, just anterior to the 3rd ventricle near the hypothalamus and is comprised of the nucleus of the diagonal band of Broca and the nucleus of the medial septum. The septum projects heavily throughout the hypothalamus and maintains rich interconnections with all regions of the hippocampus (Mesulam et al. 2003; Siegel and Edinger, 1976) as well as the substantia innominata of the limbic striatum, the amygdala, the hippocampus and reticular formation (Amaral and Kurtz 1985; Nauta, 1956; Panula et al. 1984; Swanson and Cowan, 2009). As detailed in chapter 14, the septal nuclei is implicated in memory functioning and arousal, and in this regard contributes to the formation of specific attachments through memory functioning and the modulation of emotional arousal. Moreover, like the amygdala and cingulate, the septal nuclei also produces emotional vocalizations. The septal nuclei is able to exert facilitatory or inhibitory influences on medial vs lateral hypothalamic arousal (Mogenson, 1976) and maintains a counterbalancing relationship with the amygdala particularly in regard to influences exerted on the hypothalamus (Joseph, 2012a). In addition, the amygdala acts to either facilitate or inhibit septal functioning whereas septal influences on the amygdala are largely inhibitory. For example, whereas the lateral amygdala may activate the lateral hypothalamus, the septal nuclei may activated the medial hypothalamus (Kolb and Whishaw, 1977; Mogenson, 1976; Petsche et al. 1962, 1965) and can counter lateral hypothalamic self-stimulatory activity (Mogenson, 1976). As noted, the medial hypothalamus (and the septal nuclei) are associated with unpleasant mood states. In fact, electrophysiological alterations in septal activity which correspond to subjective feelings of aversion have been reported in humans (Heath, 1976). Electrical stimulation of the septal nuclei counters and inhibits aggressive behavior (Rubenstein and Delgado, 1963) and suppresses the expression of rage reactions following hypothalamic stimulation (Siegel and Edinger, 1976). If the septal nucleus is destroyed, these counterbalancing influences are removed such that initially there results dramatic increases in aggressive behavior, including rage (Ahmad and Harvey, 1968; Blanchard and Blanchard, 1968; Brady and Nauta, 1953; King, 1958). Bilateral lesions in fact give rise to explosive emotional reactivity to tactile, visual, or auditory stimulation which can take the form of attack or flight. However, if the amygdala is subsequently lesioned, the septal rage and emotional reactivity are completely attenuated (King and Meyer, 1958). Hence, septal lesions appear to result in a loss of modulatory and inhibitory restraint which are normally exerted, in part, on the amgydala as well as the hypothalamus (McClary, 1961, 1966; Poplawsky, 1987). Because of the loss of this inhibitory restraint, the amygdala begins to promote indiscriminant socializing and, as is the case with a five month old infant, will display an extreme need for social and physical contact (Joseph, 2012a). That is, in contrast to amygdaloid lesions which produce a severe social-emotional agnosia and social avoidance and withdrawal, septal lesions produce a dramatic and persistent increase in social cohesiveness and contact seeking (Jonason and Enloe, 1971; Jonason et al., 1973; McClary, 1961, 1966; Meyer et al. 1978). With complete bilateral destruction of the septal nuclei in animals, the drive for social contact appears to be irresistable such that persistent attempts to make physical contact occurs--due in part, presumably, to the disinhibitory release of the amygdala. Septally lesioned animals will in fact seek contact with other species, including animals that might kill and eat them. If a group of septally lesioned animals are placed together, extreme huddling results. So intense is this need for contact comfort following septal lesions, that if other animals are not available they will seek out blocks of wood, old rags, bare wire frames or walls and then attempt to cuddle. Similar behaviors are demonstrated by human and non-human infant primates who are denied sufficient emotional and maternal stimulation (Joseph, 1999b,c). Among human infant, and most mammals, the desire for maternal and physical-emotional contact is a normal aspect of development.

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">Among humans with right sided or bilateral disturbances in septal functioning (such as due to seizure acitivity being generated in this region that may well involve the anterior cingulate), a behavior referred to as "stickiness" is sometimes observed. These individuals may seek to make repeated, prolonged, and often inappropriate contact with anyone who is available or who happens to be near by so as to tell them stories, jokes or merely pass the time. They don't readily take a "hint" and are difficult to "get rid of". In hospital situations they can be found intruding on other patients and their families, hanging out by the nurses station, or incessantly visiting other rooms to chat. However, in some cases, similar behaviors can be triggered by amygdala as well as anterior cingulate hyperactivation (see chapter 25). It is probably the abnormal interactions of these nuclei that account for stalking behaviors and the formation of delusional attachments to actresses, sports stars, coworkers, and so on. LIMBIC LOVE, HATE AND RELATIONSHIPS The limbic system makes it possible to experience and communicate social-emotional nuances via multiple modalities, such as is reflected in the evolution and development of emotional speech, including the ability to laugh, cry, and to express sympathy and compassion, or the desire to form or maintain an emotional attachment. It is the evolution and development of these limbic nuclei (i.e. the amygdala, septal nuclei, cingulate gyrus) and their differential rates of maturation, which in fact enable humans and other higher mammals to form long lasting emotional and loving attachments, including the need and desire for contact comfort during infancy and early childhood. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">Moreover, it is probably via the interactions mediated by these structures that emotions such as jealousy, rage or fear of abandonment are also generated, as well as feelings of possessiveness for a mate. Indeed, that some individuals respond with considerable grief, depression, anger and even uncontrollable rage when a "loved one" has ended their relationship, probably can also be explained from a limbic (infantile hypothalamic/amygdala) perspective. Unfortunately, when the limbic system has been activated in this manner, feelings of rage may soon be manifested as acts of murder. For example, the frontal lobes and the rest of the brain may be overwhelmed by these limbic upheavals and the person may act on his or her limbic attachment needs, either in an extremely dependent and despairing fashion ("Don't leave me or I'll kill myself") or violent and enraged manner ("Don't leave or I'll kill you"). Loss of love, such as occurs when a relationship ends, seconded only by jealousy and money are prime elicitors of such murderous feelings and are due to the high involvement of the limbic system in all affairs of the heart. Thus, if a person who has met another individuals primary needs for love, affection and physical intimacy were to leave, or want to end the affair, the limbic system of the male or female, being "abandoned," may respond in an infantile fashion; i.e. with desperation, frustration, anger, rage or depression and dispair -similar to the emotional stages demonstrated by children who are progressively deprived of mothering. For example, children who are temporarily separated from their mothers and placed in a hospital, childrens home, or what not, will pass through three stages of emotional turmoil, the first of which is characterized by a protest period where they frequently cry and scream for their mommy, and display signs of rage. This is followed by a stage of despair in which the child ceases to cry, loses interest in his environment and withdraws, and this too can persist for months. In the final stage he ceases to show interest in others, loses his appetite, and fails to respond to the affection offered by others and becomes quite passive and unresponsive. He may sit or lay for long periods with a frozen expression on his face, staring for hours at nothing. If the separation continues he deteriorates further and becomes physically ill and may die (Spitz 1945). In general, males are more severely affected than females (Bowlby, 1940, 1960; Spitz 1945). Those who were only temporarily removed, once they were returned home would desperately cling to their mother, follow them everywhere, and became extremely fearful when left alone even for short time periods. Those who were deprived of maternal contact for 6 months or more instead behaved in a withdrawn, depressed manner and showed no interest in and were unable to reestablish their normal attachment to their mother. According to J. Bowlby (1940, 1960), children who suffer long term or repeated separations during the first three to five years of life are usually permanently affected. However, when this same boy (or girl) grows to be an adult, instead of scrying, screaming, and raging helplessly when abandoned or neglected, he may plead as well as threaten, stalk, beat or even kill his former spouse or girlfriend and perhaps even his own children. Or, if its his job he's lost, he may threaten, attack, or kill his boss and coworkers. Fortunately, it is a small percentage of the population who act on these limbic impulses. Nevertheless, even among those humans who maintain high levels of frontal inhibitory control in regard to all matters of the heart, the amygdala, cingulate, septal nuclei, hypothalamus, inferior temporal lobe, make possible not only intense feelings of emotion for a mate or lover, but correspondingly (at least in some people), an occasional "irrational" urge to throw them in front of a train (metaphorically speaking of course). Indeed, because it provides the neurological foundation for emotion, attachment, jealously and desire, the limbic system enables human beings not only to coo words of love and sorrow but to experience all the joys, lusts, warmth, thrills, romance, passions, sexual excitement, and "craziness" of "true love." Summary In summary, during the amygdaloid maturational phase of early infant development, there is indiscriminant approach and contact seeking, which, if thwarted, may lead to emotional contact-seeking behaviors directed at inanimate objects. During the septal-cingulate stage (see below), indiscriminant social contact seeking is inhibited whereas specific attachments are narrowed, strengthened, reinforced and maintained due to the influences of these structures and the generation of fear response. However, if sufficient maternal emotional stimulation is not provided or is denied for long time periods, the infant will become enraged and then increasingly depressed. The differential rates of amygdala and septal-cingulate development are crucial in promoting survival and social interaction with significant others. If these structures matured at an earlier age and if the infant experienced fear or wariness, social contact seeking might be prevented or avoided, and the result, might be severe social emotional and limbic system abnormalities (Joseph, 1999b,c) and even death. THE CINGULATE GYRUS The five layered cingulate gyrus sits atop the corpus callosum and can be broadly divided into two segments: the anterior cingulate (areas 24, 25, and 33) which is concerned with vocalizing and emotional and motoric functioning involving the hands, and regulating autonomic and endocrine activities; and the posterior (area 23) cingulate which is involved in visual-spatial and tactile analysis as well as motor output and memory. THE POSTERIOR CINGULATE The posterior cingulate gyrus is richly interconnected with the superior parietal lobe (area 7) the parahippocampal (inferior) temporal and superior temporal lobe (area 22), frontal lobe, caudate, putamen, substantia nigra, pulvinar of the thalamus, and dorsal hypothalamus (Beleydier and Mauguiere 1980; recently reviewed in Devinksy et al. 1995). In addition, the posterior cingulate projects to the red nucleus in the midbrain (which also receives frontal motor fibers) and to the spinal cord. Presumably the posterior cingulate acts to integrate visual input with motoric output and is not concerned with emotional stimuli per se, with the possible exception of nocioceptive functions (Devinksy et al. 1995). However, the posterior cingulate may also be involved in visual-spatial and memory-cognitive activities, particularly as relates to the body and movement -hence the interconnections with the superior parietal lobe and the parahippocampal gyrus. The posterior cingulate may have, at least in part, evolved from the dorsal hippocampus (e.g. Sanides, 1964). ANTERIOR CINGULATE GYRUS The anterior cingulate (areas 24, 25, 33) is associated with processing and modulating the expression of emotional nuances, emotional learning and vocalization, the formation of long-term attachments and maternal behavior, including the initiation of motivationally significant goal directed behavior, as well as influencing and in part regulating endocrine and autonomic activities (reviewed in Devinsky et al., 1995; MacLean 2011). The anterior cingulate maintains rich interconnections with the septal nuclei, amygdala, hypothalamus, mammilary bodies, hippocampus, dorsal medial nucleus of the thalamus and the periqueductal gray (Beleydier and Mauguiere 1980; Powell, 1978; Powell et al. 1974; Muller-Preuss and Jurgens 1976), as well as with the limbic striatum, caudate and putamen and the frontal motor areas. The anterior cingulate thus appears to be a supra-modal area that is involved in the integration of motor, tactile, autonomic, and emotional stimuli, as well as with the production of emotional sounds (see below) and the capacity to experience psychological "pain and misery." In fact, the cingulate has long been associated with the experience of psychic and even physical pain (e.g. identifying the affective attributes of noxious and psychic stimuli). Hence, during the 1930's and 1940's, bilateral cingulotomies were frequently performed to eliminate severe depressive and psychotic states as well as obsessive compulsive tendencies involving the hands (Le Beau, 1954; Whitty and Lewin 1957). However, following surgery, patients tended to become apathetic, emotionally blunted and/or socially and emotionally inappropriate or unresponsive. Nevertheless, more recently it has been reported that 25% to 30% of patients with obsessive-compulsive disorder who were unresponsive to medication and behavioral treatment, significantly improve following cingulotomy (Baer et al. 1995), though these authors stress surgery is "a last resort treatment." THE CINGULATE GYRUS AND EMOTIONAL FREE WILL Electrical stimulation of the anterior cingulate can induce feelings of anxiety, pleasure and fear (Meyer et al. 1973) as well as changes in heart and respiratory rate and blood pressure accompanied by pupil dilation, gonadal and adrenal cortical hormone secretion, penile erection, and aggression (Buchanan and Powell 1982; Devinsky et al. 1995; MacLean 2011). Stimulation also induces a wide range of divergent vocalizations including growling, crying, high pitched cackling, and sounds similar to an infant's separation cry. THE ANTERIOR CINGULATE GYRUS AND EMOTIONAL SPEECH The amygdala is able to produce complex social-emotional vocalizations via the stria terminals and amygdalafugal pathways to the hypothalamus and periaqueductal gray which acts on the oral-laryngeal musculature. The amygdala also increasingly interacts with the rapidly maturing cingulate gyrus which is one of the most vocal structures of the brain (Jurgens, 2011, 2012; MacLean, 2011; Ploog, 2012; Robinson, 1967, 1972) and which becomes activated in response to and when producing human speech (Passingham, 1997; Paulesu et al., 1997; Peterson et al., 1988). For example, the anterior cingulate (as well as the left frontal lobe) become highly active when generating as many words as possible for a given category, e.g. words beginning with "F" (Frith and Dolan, 1997). The anterior cingulate gyrus is also directly linked to the neocortical expressive speech areas located in the left and right frontal lobe, as well as with the hypothalamus and periaqueductal gray (Powell, 1978; Powell, Akagi, and Hatton, 1974; Jurgens, 2011, 2014)--which explains why the anterior cingulate and left frontal lobe become active simultaneously during language tasks (Frith and Dolan, 1997; Peterson et al., 1988). Indeed, Broca's expressive motor-speech (and oral-facial/hand) area in the left frontal lobe, and the emotional-melodic speech (and oral-facial/hand) area in the right lateral frontal lobe, appear to have evolved from the anterior cingulate gyrus/medial frontal lobe (Joseph, 1999e). Therefore, the right and left frontal lobes responds to cingulate (and posterior neocortical) impulses by vocalizing. If the anterior cingulate/medial frontal lobe were destroyed, the patient would become mute (Barris and Schuman, 1953; Devinksy et al. 1995; Joseph, 1999a; Laplane et al., 1981; Tow and Whitty, 1953). Among its many functions, the anterior cingulate (Brodmann's areas 24, 25, 33) is associated with processing and modulating the vocal expression of emotional, melodic, and prosodic nuances, emotional learning, identifying the affective attributes of noxious psychic stimuli, maternal behavior, separation anxiety, and the formation of long-term attachments (Devinsky, Morrell, and Vogt, 1995; Joseph, 1999b; MacLean 2011; Powell, 1978). As based on functional imaging, the anterior cingulate also becomes activated by hot, painful, and noxious stimuli (Casey et al., 2014; Coghill et al., 2014), and, as noted, has been considered by some to be the seat of pain and misery. Depth electrode stimulation of the anterior cingulate can induce feelings of anxiety, pleasure and fear as well as a wide range of divergent vocalizations including growling, crying, high pitched cackling, laughing, and sounds similar to an infant's separation cry (Devinsky et al. 1995; Jurgens, 2011; MacLean 2011; Meyer et al. 1973; Robinson, 1967). The anterior cingulate also assists in setting thresholds for vocalization (Jurgens and Muller-Preuss, 1977; Robinson, 1967), including modulating some of the prosodic and melodic features which characterize different speech patterns, e.g. happiness vs sadness, and thus laughing vs crying. The vocalizing capabilities of the cingulate are made possible via subcortical connections with the periaqueductal gray (Jurgens 2011, 2014), and its axonal projections to the right and left frontal speech areas. Whereas vocalizations triggered by excitation of the amygdala, hypothalamus, or septal nuclei are usually accompanied by mood-congruent behaviors (Gloor, 1960; Jurgens, 2011; Robinson, 1967; Ursin and Kaada, 1960) the cingulate is capable of producing exceedingly complex social emotional vocalizations which sometimes have no bearing on the organism's mood or true emotional state (Jurgens, 2011; Jurgens and Muller-Preuss, 1977; Meyer et al. 1973). In addition, completely different emotional calls can be elicited from electrodes which are immediately adjacent (Jurgens, 2011). Thus the cingulate is capable of considerable vocal flexibility and apparently enables an individual to modulate the emotional-prosodic-melodic components of speech so that one's true feelings can be disguised or emphasized in order to produce sounds suggestive of, for example, sarcasm, incredulity, or hilarity. The anterior cingulate may well contribute to the "deceptive" vocalizations and behaviors demonstrated by innumerable mammalian and avian species (e.g., Hauser, 1997), such as when attempting to lure a predator away from one's helpless infants. Conversely, however, the anterior cingulate, coupled with the right frontal lobe, may also be responsible for the failure to hide one's true feelings, thus generating the complaint: "Its not what you said, but the way you said it!" As noted, if the anterior cingulate were destroyed, of if the pathways linking this structure with the periaqueductal gray were severed, the individual would become mute (Barris and Schuman, 1953; Devinksy et al. 1995; Jurgens, 2011; Laplane et al. 1981; Tow and Whitty, 1953). However, if the cingulate and surrounding medial tissue were mildly injured, or became abnormally active, emotional-prosodic speech would become exceedingly abnormal and patients may stutter and repeat words such that, in the extreme, they may uncontrollably babble (Devinksy et al. 1995; Dimmer and Luders, 1995; Penfield and Welch, 1951). THE CINGULATE, THE SEPARATION CRY AND "MOTHERESE" The medially located cingulate gyrus begins to myelinate around the second postnatal month and achieves an advanced stage of myelination by the end of the first year (Debakan, 2000; Gibson, 1991; Yakovlev and Lecours, 1967); around the same time the amygdala increasingly vocalizes feelings of fear. However, in addition to fear, the anterior cingulate contributes to the experience of unpleasant feelings (Casey et al., 2014; Coghill et al., 2014) including separation anxiety and vocalizes a separation cry which is similar if not identical to that produced by a frightened infant (MacLean 2011; Robinson, 1967). In fact, abnormal activity in the anterior cingulate has in some cases induced not just anxious vocalizations, but infantile behavior, such as assuming the fetal position (Devinksy et al. 1995).

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The anterior cingulate is thus responsible for producing complex emotional-prosodic vocalizations, including, perhaps, the prosodic variations which mothers employ when speaking to their babies and vice versa; i.e. "motherese." As is well known, considerable vocalizing typically occurs between mothers and their infants; and the infants of many species will often sing along or produce sounds in accompaniment to those produced by their mothers (Bayart et al., 2011; Hauser, 1997; Jurgens, 2011; Wiener, Bayart, Faull, and Levine, 2011). These interactions appear to be limbically mediated and reinforce and promote mutual vocalization, attachment behaviors, and may contribute to the development of language. Among animal and human mothers, much of this initial mutual sound production consists of exaggerated emotional prosody (Cooper and Aslin, 2011; Fernald, 1991, 2012; Fernald et al., 1989; Hauser, 1997; Jurgens, 2011); i.e. "limbic language." <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif;">The cingulate is also sexually differentiated (MacLusky, Clark, Naftolin and Goldman-Rakic 1987; MacLusky et al.,2014). Thus there is a "male" vs a "female" cingulate which in turn likely contributes to sex differences in melodic speech patterns as well as in "maternal" vs "paternal" behaviors. For example, regardless of culture, mothers not only produce emotional-prosodic-melodic vocalizations but emphasize and even exaggerate social-emotional, and melodic-prosodic vocal features when interacting with their infants (Fernald, 2012; Fernald, et al. 1989; Nakazima, 1975). Presumably, it is these limbic foundations which explain why the acoustics of these nuances are basically identical regardless of culture (Nakazima, 1975), and why even mothers or infants who are born deaf produce these same prosodic vocalizations when speaking to their deaf babies (Oller et al., 1985; Woll and Kyle, 1989). These emotional-melodic vocalization greatly influence infant-emotional behavior and attention as infants not only produce but prefer and are more responsive to these exaggerated prosodic vocalizations (Cooper and Aslin, 2011; Fernald, 1991). In fact, by 5 months of age infants become quite adept at perceiving and distinguishing between different emotional vocalizations so as to determine the mood state and intentions of the speaker (Fernald, 1993; Haviland and Lelwica, 1987). Likewise, mothers are generally able to determine the mood and desires of her 5-month old offspring when it produces similar emotional vocalizations (D'Odorico, 1984; Wolff, 1969). In many respects these mutual mother-infant social-emotional interactions appear to be a reflection of the limbic system of the mother communicating with the limbic system of her infant. The infant-neocortex is much too immature to comprehend non-emotional words and sentences. The female limbic system (and the right frontal-temporal speech areas) are in fact adapted and organized so as to promote social-emotional communication with her young, and with each other. That is, the cingulate gyrus, amygdala and hypothalamus are sexually differentiated such that there is a "male" and a "female" limbic system (see chapter 13). Being in possession of a "female" limbic system presumably confers a superior ability to perceive and express social-emotional nuances and vocalizations (Joseph, 2000a); capacities at which females excell (Burton and Levy, 1989; Brody, 1985; Buck, 1977, 1984; Buck, Miller, and Caul, 1974; Fuchs and Thelan, 1988; Heller and Levy, 2012; Soloman and Ali, 1972; Strayer, 1980). Indeed, in contrast to males, females are not only more emotionally perceptive and expressive, but tend to employ 5-6 different prosodic variations and utilize the higher and fluctuating registers when conversing (Joseph, 1993, 1999e), especially with their infants (Fernald, 2012; Fernald, et al. 1989). Human (as well as non-human) infants are not only more responsive to the emotional-prosody conveyed by a female voice, but are most responsive to the higher as well as fluctuating registers (Fernald, 1985; Hauser, 1997). However, in contrast to the infant, adult females (and males) also rely on the neocortices of the right frontal-temporal lobe to produce and comprehend emotional-melodic-prosodic vocalization. As noted, over the course of evolution the anterior cingulate appears to have contributed to the evolution of the frontal motor-speech areas, whereas the auditory areas in the superior temporal lobe appear to be evolutionary derivatives of as well as richly interconnected with the amygdala (Joseph, 1999e). The frontal and temporal auditory areas, however, do not begin to significantly mature until around the first year after birth; a process which can take 7 to over 20 years to complete (Blinkov and Glezer, 1968; Brody, et al. 1987; Conel, 1939, 1941; Flechsig, 1901; Huttenlocher, 2011; Yakovlev and Lecours, 1967). MATERNAL BEHAVIOR & THE EVOLUTION OF INFANT SEPARATION CRIES Sharks, teleosts, amphibians, and reptiles possess a limbic system, consisting of an amygdala, hippocampus, hypothalamus, and septal nuclei (see chapter 5). It is these limbic nuclei which enable a group of fish to congregate and "school", and which makes it possible for reptiles to form territories which include an alpha female, several sub-females, and a few juveniles. These nuclei promote social attachment and interaction. However, sharks, fish, and the first amphibians and reptiles, like their modern counterparts lacked the four to five layered cingulate gyrus. Moreover, these creatures do not possess an inner ear or true middle ear, though amphibians and reptiles are attuned to hear low level vibrations and sounds, such as croaking, tails thumped on the ground, and a few distress calls and those of contentedness. Limbic language capabilities are not well developed in these creatures. As they also lack a cingulate gyrus, amphibians and most but not all reptiles show little or no maternal care, and rarely vocalize. They will also greedily cannibalize their infants who in turn must hide from their parents, and other reptiles, in order to avoid being eaten (MacLean, 2011). When reptiles began to differentiate and evolve into the repto-mammals some 250 million years ago, and then, twenty-five million years later, when the first tiny dinosaurs (who diverged from a different line of reptiles, the theocondants) began to roam the Earth, major biological alterations occurred involving cranial and post-cranial skeletal structure, mammillary development, thermo-regulation, sexual reproduction, and limbic system function and structure (Bakker, 1971; Brink, 1956; Broom, 1932, Crompton & Jenkins, 1973; Duvall, 1986; Paul, 1988; Quiroga, 1980; Romer, 1966) --all of which coincided with tremendous advances in the ability to engage in audio-vocal communication and the capacity to nurse the young (chapter 5). It was not until the appearance of the the therapsids, around 200 to 150 million years ago, that mammilary glands, and thus the capacity to nurse, came into being (Duvall, 1986). It was at this time that the middle ear began to undergo tremendous modification and the first rudiments of an inner ear developed (Broom, 1932; Brink, 1956; Crompton & Jenkins, 1973; Romer, 1966). Although the hypothalamus, septal nuclei, and amygdala continued to evolve, it was also around this time that the cingulate gyrus began to appear and increasingly enshroud the dorsal surface of the limbic forebrain -an event which corresponded with the appearance of nursing nipples (Duvall 1986) and the inner ear. When this began to occur, sounds came to serve as a means of purposeful and complex communication, not only between potential mates or predator and prey, but between a mother and her infant (Joseph, 1993, 2014; Maclean, 2011). This ability in turn was probably made possible by the amygdala and in particular, the evolution of the four to five-layered transitional neocortex, the cingulate gyrus. As noted, it is the limbic system and the interactions of limbic nuclei such as the amygdala and the cingulate gyrus which not only stimulates the desire to communicate, but to form attachments, social groups, and eventually, the formation of the family. In fact, many of the late repto-mammals, as well as some dinosaurs and the later appearing therapsids, lived in packs or social groups, and presumably cared and guarded their young for extended time periods lasting until the juvenile stage (Bakker, 1971; Brink, 1956; Crompton & Jenkins, 1973; Duvall, 1986; Paul, 1988; Romer, 1966). Presumably long term attachments were made possible via the evolution of the anterior cingulate. As also noted, the first appearance of rudimentary nipples coincided with therapsid development. Hence, one of the hallmarks of this evolutionary transitional stage, some 200 million years ago, was the cingulate gyrus and the first evidence of nursing, maternal feeling, and the creation of large social groups and hunting packs, and what would become the family. MOTHER INFANT VOCALIZATION Among mammals and primates the production of sound is very important in regard to infant care, for if an infant becomes lost, separated, or in danger, a mother could not quickly detect this by olfactory-pheromonal cues alone. These conditions would have to be conveyed via a cry of distress or a sound indicative of separation fear and anxiety; which would cause a mother to come running to the rescue. Conversely, vocalizations produced by the mother would enable an infant to continually orient and find its way back if perchance it got lost or separated. Hence, the first forms of complex limbic social-emotional communication may well have been first produced in a maternal context. As noted, considerable vocalizing typically occurs between mothers and their infants (be they human, primate, or mammal); and the infants of many species will often sing along or produce sounds in accompaniment to those produced by their mothers. These mutual interactions reinforce and promote mutual vocalization which is often initiated by the mother. In fact, primate females are more likely to vocalize when they are near their infants versus non-kin, and infants are more likely to vocalize when their mother is in view or nearby (Bayart et al. 2011; Jurgens, 2011; Wiener et al. 2011). Similarly, infant primates will loudly protest when separated from their mother so long as she is in view and will quickly cease to vocalize when isolated (Bayart et al. 2011; Wiener, et al. 2011). However, adult males are also more likely to call or cry when in the presence of their mother or an adult female vs an adult male (see Jurgens, 2011). It thus appears that the purpose of these vocalizations are to elicit a vocal response from mother, or an adult female, who in turn is likely to respond with soothing limbic language. Hence, ontogentically and phylogenetically, the initial production of emotional sounds is limbically based, and increasingly, over the course of evolution, and as evident during early development, the production of these sounds is associated with maternal-infant care, and/or interactions with an adult female. As noted, the cingulate is sexually differentiated (MacLusky et al., 1987, 2014), and regardless of culture, human mothers tend to emphasize and even exaggerate social-emotional, and melodic-prosodic vocal features when interacting with their infants (Fernald, 2012; Fernald et al., 1989), which in turn appears to greatly influence infant emotional behavior and attention (Fernald, 1991). Similarly, human infants prefer listening to and are more responsive to these exaggerated limbic vocalizations, as compared to "normal" adult speech patterns (Cooper and Aslin, 2011) particularly when produced by a female; i.e. by a female cingulate gyrus. FEMALE SUPERIORITIES IN LIMBIC LANGUAGE In addition to the cingulate, the amygdala and hypothalamus are also sexually differentiated (Allen and Gorski, 2012; Allen et al., 1989; Blier et al., 1982; Gorski et al. 1978; Goy and McEwin, 1980; Raisman and Field, 1971; Swabb and Fliers, 1985; Swabb and Hoffman, 1988). In addition, the rope of nerve fibers which interconnect the right and left amygdala and inferior temporal lobes (the anterior commissure) is 18% larger in females than males (Allen and Gorski, 2012), which in turn likely contributes to sex differences in language, emotion, and maternal vs paternal behavior. Thus, females tend to produce a greater range of limbic (social-emotional) vocalizations than males (Glass 2012; Joseph, 1993, 2000a; Tannen 1991) and they tend to employ 5-6 different prosodic variations and to utilize the higher registers when conversing. They are also more likely to employ glissando or sliding effects between stressed syllables (Brend, 1975; Coleman, 1971; Edelsky, 2009). Men tend to be more monotone, employing 2-3 variations on average, most of which hovers around the lower registers (Brend, 1975; Coleman, 1971; Edelsky, 2009). Even when trying to emphasize a point males are less likely to employ melodic extremes but instead tend to speak louder. Perhaps this is why men are perceived as more likely to bellow, roar, or growl, whereas females are perceived as more likely to shriek, squeal, coo, and purr. Nevertheless, although influenced by sex differences in the oral-laryngeal structures, these differential capacities are also reflected in the greater capacity of the female brain to express and perceive these nuances (chapter 7), which also appears to be the case in female primates. Thus female monkeys and apes are more vocal and engage in more social vocalizations, and in fact vocalize more often that males who in turn are more likely to vocalize when threatening or engaged in dominance displays (Cross and Harlow, 1965; Erwin, 1980; Fedigan, 2012; Goodall, 1986, 2011; Mori, 1975; Mitchell, 2009). It has been repeatedly demonstrated that human females are also more emotionally expressive, and are more perceptive in regard to comprehending emotional verbal nuances (Burton and Levy, 1989; Hall, 1978; Soloman and Ali, 1972). This superior sensitivity includes the ability to feel and express empathy (Burton and Levy, 1989; Safer, 1981). From childhood to adulthood women appear to be much more emotionally expressive than males in general (Brody, 1985; Burton and Levy, 1989; Gilbert, 1969); abilities which confer upon her a greater emotional sensitivity to the needs and feelings of others, especially her babies. These superiorities assist her in being a good mother. MATERNAL BEHAVIOR, ATTACHMENT, AND THE FEMALE LIMBIC SYSTEM It has been proposed that these limbic system sex differences are responsible for and are an evolutionary consequence of woman's role in bearing and rearing children and the female desire to form long term attachments, and engage in maternal care and verbal communication (Joseph, 1993). Female humans, primates and mammals apparently find these activities rewarding in-themselves, due to these same limbic system sex differences. That is, given that the sexually differentiated anterior cingulate, at least in part, evolved in a maternal context and promoted the development of maternal feelings and long term mother-infant attachment, whereas the amygdala and hypothalamus are also sexually differentiated, it appears that these structures may account for why human and non-human female primates differentially respond and desire to nurture, hold, cuddle, and stare at infants. Indeed, female humans, chimps, baboons and rhesus macaques cuddle more and more closely, and are cuddled more by their sisters, mothers and other females (Jensen et al., 1968a, Hansen, 1966; Mitchell, 1968; Goodall 1971, 2011), whereas males are much more resistant to being held, and will kick and fuss, and actively attempt to escape their mothers much more so than females (Elia, 1988; Fedigan, 2012; Freedman, 1974, 1980; Mitchell, 1968, 2009; Goodall 1971, 2011; Kummer, 1971). In part this sex differences also reflects a struggle against potential physical domination which most males find aversive (Joseph, 1993). Hence, be it a male dog, chimpanzee, baboon, or child, they are far more likely than females to struggle, squirm, or resist attempts to hold or pick them up, and may even respond as if they find it aversive. Mothers are therefore more willing to hold female babies and for longer time periods as they are also easier to calm and are more fun to hold as they seem to enjoy it more than males. Since females demonstrate greater social responsiveness and are more likely to employ facial, vocal and social signals, mothers are more likely to physically, socially and vocally interact with their infant daughters and vice versa (Moss, 1974). Being similarly socially inclined, mothers find it more socially rewarding and enjoyable to interact with their daughters who are also in possession of a "maternal" (albeit immature) limbic system and cingulate gyrus. Be it a female chimpanzee, baboon, rhesus macaque, or human, females also begin to demonstrate an extraordinary interest in babies and in play-mothering during even the earliest phases of their own childhood (Devore, 1964; Elia, 1988; Fedigan 2012; Goodall 1971, 2011; Jolly 1972; Kummer, 1971, Mitchell, 2009; Strum, 1987; Suomi, 1972). When girls play together, much of their fantasy and conversation concerns fashion and making out and revolves around adult relationships, including the raising of a family and the behavior and misbehavior of children (their dolls). Babies are of enormous interest to females, be they human, ape or monkey, and social primates and female humans who have babies usually become tremendously popular and the center of attention (Fedigan 2012; Jolly 1972, Mitchell 2009, Strum ,1987). Even among women enslaved in a harem, once she becomes pregnant and has a child, her status is quickly and permanently elevated. Mothers, grandmothers, young and adolescent females, and even women who describe themselves as "feminists" show much more interest in babies than do men, even when the baby is not their own (Azhn-Waxler et al., 2003; Berman, 2011; Berman and Goodman, 1984; Blakemore, 1981, 1985, 2011; Frodi & Lamb, 1978; Melson and Fogel, 1982; Nash and Fledman, 1981). Adolescent girls spend significantly more time talking about new baby's than boys (Berman, 2011), and mothers spend more time talking about the baby with their daughters than their sons (Berman, 2011). Girls not only talk more but play and care for their infant sisters and brothers significantly more and show consider amounts of nurturant interest in the babies well being (Blakemore, 2011) even when there has been no request or pressure to do so. Indeed, girls often demonstrate an intrusive interest in babies (Berman, 2003), and will give infants much more care than they require (Ainsworth & Wittig, 1969), as if often the case with mothers (Stewart, 2011). These behaviors also appear to be limbically mediated, as they are demonstrated by females of other species. Non-human female primates, be it gorilla, chimpanzee, baboon, rhesus macaques, lemur, and so on, will eagerly seek to groom, cuddle, and carry not only their own infants but those of other females (Jolly, 1985; Devore, 1964; Kummer 1971, Strum 1987; Suomi, 1972; Mitchell, 2009; Goodall, 1971). These primates may also spend all day passing them back and forth. Like human females, some will even steal these infants. Those female primates who show the greatest interest, however, are young females who had not yet had babies. Moreover, among almost all social primates, the birth of a new baby has an extremely excitatory effect on all the other females of the troop who will gather around and touch, stare, hold, and cuddle it. This female interest, of course, is certainly quite adaptive, at least for those living in the dangerous condition of the wild for it insures that if a mother dies another will adopt her baby. Such behavior is obviously not the result of sexist training for it is typical of almost all social female primates, whereas males, including young males show relatively little interest in babies. For example, boy chimpanzees show little interest in their younger infant siblings, whereas girl chimps become increasingly fascinated and will hold and cuddle them and will attempt to model their mother's interactions with the infant (Goodall, 1971). If a new mother dies but her baby has older male siblings, less than 25% will adopt the little orphan whereas females siblings are quite anxious and happy to take this role. THE MALE LIMBIC SYSTEM AND INFANT CARE With the exception of the baboon (Rowell et al., 1968; Kummer, 1968, 1971; Mitchell, 1968, 2009, Fedigan, 2012), lack of interest in infants is characteristic of most social male primates and almost all male mammals, reptiles, amphibians and fish, as well as human fathers and men and boys in general who generally have little or no interest in babies and generally provide little or nurturant care for their own or the children of others (Rossi, 1985; Gordon and Draper, 1982). In fact, be it male chimps attacking another troop, or male humans attacking other humans, infants are often the victim of male aggression. Males will kill other humans including the babies of those who have done them no harm.

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Of course, there are always exceptions; particularly among males who may possess a "female" limbic system. Rather, like other social primates, boys seek boys for playmates and engage in considerable amounts of rough housing, wrestling, and hitting; behavior that is completely inappropriate in regard to infant interactions. When boys or male primates begin to separate from their mothers, they show no interest in younger siblings but seek out adolescent and adult males to play with. Although they may on occasion seek nurturance they seldom provide it in return. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Human males and fathers rarely behave in any manner that approximates normal female maternal behavior (Belsky et al., 1984; Clarke-Stewart, 1978; Frodi et al., 1982) as this is simply not an activity they find interesting, pleasurable or rewarding. This is why, for example, child care professions and those jobs involving high levels of child interactions, such as elementary school teacher, are overwhelmingly made up of women (Gordon and Draper, 1982); a function not of pay but lack of heterosexual-male interest (Blakemore et al., 1988). Rather, fathers and adult heterosexual males tend to express interest in younger males (and females) only when they reach adolescence, and this is also true of most male primates. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Given that these sex differences are obviously innate, it could therefore be argued that in contrast to male humans, primates, and mammals who have little or no interest in child care, that the female limbic system is designed to promote these interests. Just as the male limbic system rewards males for engaging in competitive and aggressive actions (see chapter 13), the female limbic system probably generates rewarding feelings, coupled with appropriate emotional vocalizations, when females look at, hold, care for, and form attachments to their babies, infants, young children. Although this has yet to be determined, the female limbic system probably contains nuclei, neural networks, and individual neurons which respond selectively to infant visual and auditory related stimuli; e.g. baby faces, infant cries. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Again, consider that the anterior cingulate, in part, evolved in a "maternal" context and acts to promote the development of maternal behavior and mother-infant communication. Indeed, sex specific structural differences in the limbic system probably account in large part for most all sex differences in emotionality and related behavior, including childcare, the desire to have and nurture babies, and the greater female propensity for developing affective and mood disorders. However, these sex differences also make her a more communicative mother. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">CINGULATE MATERNAL INFANT COMMUNICATION <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The anterior cingulate gyrus, in conjunction with the amygdala and right frontal lobe, appears to provide the foundation for mother-infant communication, the generation of separation anxiety, as well as the desire to provide as well as receive prolonged maternal care (Davidson and Fox, 1989; Joseph, 1993, MacLean, 2011). Long-term mother-infant communication and prolonged maternal care is unique to human and non-human primates, as well as some mammals (e.g. Hauser, 1997), and appears to be directly associated with the rather recent evolution of the five-layered neo-limbic mammalian cingulate gyrus (Joseph, 1993, MacLean, 2011). Again, animals lacking the more recently evolved cingulate gyrus, but who possess a hypothalamus, amygdala, and brainstem (e.g. such as reptiles, amphibians, teleosts, and sharks) fail to provide even short-term maternal care and sometimes cannibalize their young. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted, with the evolution of the cingulate and mammal-like therapsids, it appears that vocalization came to serve as a means of complex communication, not only between potential mates or predator and prey, but between mother and infant (for related discussion see MacLean, 2011; Ploog, 2012). Hence, in humans, whereas the anterior cingulate is one of the most vocal structures of the brain and becomes highly active when speaking (Frith and Dolan, 1997; Passingham, 1997; Paulesu et al., 1997; Peterson et al., 1988), destruction of the anterior cingulate abolishes emotional speech production, and results in severe abnormalities in social and emotional behavior and a loss of maternal responsiveness (Barris and Schuman, 1953; Laplane et al. 1981; Maclean, 2011; Tow and Whitty, 1953). Behavior, in fact, becomes reptilian, and human and non-human primates become mute, cease to groom or show acts of affection, and treat their infants as if they were inanimate objects that might be walked on and discarded. In non-human primates, the majority of infants whose mothers have suffered anterior cingulate destruction, die from lack of care (MacLean, 2011). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">BABBLING, LIMBIC LANGUAGE, AND NEUROANATOMICAL MATURATIONAL EVENTS <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The capacity to vocalize is initially the province of the brainstem and midbrain periaqueductal gray which responds reflexively to the immature hypothalamus. Thus, for the first 30-days following birth, infants tend to cry, cough, belch, grunt, and express displeasure and distress. These initial sounds are likely produced reflexively by the periaqueductal gray, perhaps in reaction to the hypothalamus which may trigger crying when experiencing hunger or thirst. However, as the brainstem, hypothalamus, and then the amygdala and cingulate continue to mature the infant begins to babble and increasingly expresses feelings of pleasure and other social-emotional nuances.

<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For the first six months of life, with the exception of the somatomotor areas, much of the neocortex is so immature that its influences are negligible. However, the somatomotor areas begin to mature quite early; reflected in dendritic and pyramidal neocortical development (Flechsig, 1901; Joseph, 1982; Gibson, 1991; Gilles et al. 2003; Scheibel, 1991) and the growth and myelination of the corticospinal tracts which invades the brainstem several months before birth (Kertesz and Geschwind, 1971; Yakovlev and Rakic, 1966). However, the corticospinal tracts (which project from the motor areas to the brainstem and spinal cord), take well over a year to reach advanced levels of myelination (Yakovlev and Lecours, 1967). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The myelination of the corticospinal tract coincides with the descent of the larynx, the myelinization and development of the amygdala and the amygdalafugal brainstem pathway, and later, the maturation of the cingulate gyrus and its pyramidal brainstem pathways (Debakan, 2000; Langworthy, 1937; Yakovlev and Lecours, 1967; Yakovlev, and Rakic, 1966). These overlapping maturational and physical events also coincide with vocal development and the onset of early and late babbling followed by canonical and jargon babbling. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Early Babbling, Probable Meanings, and Prosody <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">By 2-3 months of age amygdala-brainstem pyramidal fibers as well as corticospinal axons have already begun to myelinate. These maturational events coincide with an initial shift in the emotional utterances of the infant which become progressively complex and prosodic and increasingly subject to sequencing and segmentation. The infant begins to "coo," "goo," and babble. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, as the amygdala (followed by the anterior cingulate) matures and begins establishing hierarchical control over the hypothalamus, midbrain periaqueductal gray, and the brainstem masticatory centers with which it maintains a massive fiber pathway (Takeuchi et al., 1988) the infant will laugh, becomes increasingly oral, displays genuine pleasure, stares and smiles at the human face, and while so doing, will phonate and babble. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">This early babbling stage generally involves the repetition of pleasant friction and voicing sounds which tend to be produced while making face-to-face and eye-to-eye contact and while engaged in social interaction (Kent and Miolo, 1995). Moreover, whereas the expression of pleasant sounds are in the ascendant, crying tends to become less frequent but more variable in tone, and can be differentiated into requests, calls, and sounds of discomfort (D'Odorico, 1984; Wolff, 1969). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As the amygdala, corticospinal tracts, and cingulate continue to mature, and the larynx continues to assume an adult pattern of orientation, the infant not only babbles but vocalizes a variety of sounds which increasingly convey probable meanings which may signify to the listener a variety of diffuse feelings and needs (D'Odorico, 1984; Wolff, 1969). Infants produce different noncry vocalizations depending on context and in reaction to people vs objects. The 3-4 month old infant can in fact produce at least four different pitch contours differening in fundamental frequency, each of which conveys probable meanings regarding affective state (Fernald, 2012; Hauser, 1997). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, if the 4 month old infant coos and babbles "mama," to the primary caretake (and depending on context, facial expression, and prosody/fundamental frequency) this may be interpreted to mean: "mama come here," "mama I hurt," "mama I thirst," etc. (e.g., D'Odorico, 1984; Fernald, 2012; Joseph 1982, Piaget, 1952; Vygotsky, 1962; Wolff, 1969). Hence, although the infant's utterances are not referential and may at times represent little more than the random universal babbling produced by all infants, they can also convey meaning and serve as a means of communicating with the primary caretaker (see Fernald, 2012; Hauser, 1997, for related discussion). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">MATURATION OF THE AMYGDALA, CINGULATE, AND EARLY AND LATE BABBLING <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As detailed above, the increased complexity of the infant's utterances likely reflect the maturational influences of the amygdala, and later, the cingulate, coupled with physiological/anatomical changes in the position and orientation of the larynx. These same maturational events are also correlated with different babbling stages. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Activation of the amygdala can trigger lip smacking, rhythmic jaw movement, babbling, and manidibular-teeth "chattering" (Gloor, 1997), which, when coupled with sound production may induce babbling. Infant's display similar behaviors, which is presumably a direct consequence of the immaturity of the amygdala and its projections to the masticatory centers in the brainstem. Indeed, early babbling appears to be a direct function of reflexive and spontaneous jaw movement (e.g, MacNeilage and Davis, 2011; Moore and Ruark, 1996; Weiss, 1951) and lip smacking. Hence, early babbling may reflect immature amygdala (as well as amygdala-striatal and motor neocortical) influences on the brainstem masticatory centers and the periaqueductal gray which reflexively triggers the oral musculature thereby inducing rhythmic movement of the jaw. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">"Early" babbling is soon replaced by "late" babbling which has its onset around 4 months of age (de Boysson-Bardies et al.,1981; Oller, 1980; Oller and Lunch, 2012). Late babbling is sometimes described as "repetitive babbling" (Mitchell and Kent, 2011), and at later stages of development may include the repetitive production of CV syllables in which the same consonant is repeated, such as "dadada." As noted, electrical stimulation in the cingulate and surrounding medial frontal tissues can trigger the repetitive babbling of certain words and sounds, such as "dadadada" (Dimmer and Luders, 1995; Penfield and Welch, 1951). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The development of late babbling also occurs in conjunction with the infant's increased ability to produce sophisticated social-emotional nuances, and appears to be associated with increasing cingulate (as well as amygdala) influences. For example, around 4-months, the infant's intonational-melodic vocal repertoire becomes more elaborate and tied to a variety of specific feeling states (Piaget, 1952); which may reflect increasing amygdala maturational dominance. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, over the ensuing months vocalizations also begin to assume an imitative quality (Nakazima, 1980) which are often context specific but which do not necessarily reflect the infant's internal state--a characteristic also of cingulate vocalizations. Some infant vocalizations are produced in mimicry and in play (Piaget, 1952), and the cingulate is also associated with mimicry and play behavior (MacLean, 2011). The late babbling stage has also been repeatedly described as a form of "sound play;" an activity which increasingly contributes to phonetic development (de Boysson-Bardies et al. 1981; Ferguson and Macken, 2003). As the cingulate is associated with mimicry and the onset of play behavior (MacLean, 2011) and since the production of these sounds do not necessarily reflect the infant's true emotional state, the cingulate, therefore, is implicated in all aspects of the late babbling stage. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As noted, late, repetitive babbling consists of sequences of CV syllables in which the same consonant is repeated, e.g. dadadada. However, infants will also produce what has been referred to as non-duplicated, variegated, and concatenated babbling (see Oller, 1980; Mitchell and Kent, 2011). That is, they will increasingly vocalize phonetically-varied-multisyllables which are periodically inserted into what is otherwise a repetitive sequences of CV syllables. These latter tendencies in fact, appear to be present even at the onset of the late babbling stage (Mitchell and Kent, 2011). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Repetitive, late babbling increases in frequency until around the seventh to tenth month of postnatal development (de Boysson-Bardies et al. 1981; Ferguson and Macken, 2003; Nakazima, 1980; Oller, 1980; Oller and Lunch, 2012), at which point the tendency to produce phonetically varied multisyllables becomes dominant. Thus the late babbling stage comes to be largely replaced by what has been termed "variagated" or "canonical" babbling (Oller, 1980; Oller and Lunch, 2012) which in turn is followed by "jargon" babbling (around 12 months). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Likewise, during these latter babbling periods the infant is also able to express fear, separation anxiety, and a variety of subtle social-emotional nuances. Although it appears that there is considerable overlap between these so called stages (e.g. Mitchell and Kent, 2011), the onset and increased frequency of late babbling followed by the increased production of variagated/canonical and then jargon babbling (Nakazima, 1980; Oller, 1980; Oller and Lunch, 2012), coincides with and appears to reflect the (overlapping) maturational influences of the amygdala followed by the anterior cingulate and then the frontal motor neocortice (which produce true speech). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">BABBLING AND AMYGDALA, CINGULATE, NEOCORTICAL MATURATION <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The maturation of the amygdala is associated with the onset of early babbling, whereas the anterior cingulate likely contributes to the development of late (repetitive) babbling, and the increased production of canonical/variagated babbling. These latter maturational events, however, also correspond to those taking place in the motor areas of the neocortex and may represent increasing pyramidal influences on the brainstem and oral-laryngeal musculature. In fact, jargon babbling appears to be a function of the immature neocortical somatomotor areas slowly gaining control over the limbic system, midbrain inferior-colliculus, and periaqueductal gray (see also Herschkowitz et al. 1997). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">For example, pyramidal fibers from the somatomotor neocortex to the brainstem become increasingly well myelinated from 4 to 12 months of age (Debakan, 2000; Yakovlev and Lecours, 1967). Likewise, the somatomotor areas of the neocortex begin to rapidly mature around the first postnatal year (Brody et al. 1987; Chi, Dooling, and Gilles, 1977; Gilles et al. 2003; Scheibel, 1991, 1993). Hence, the neocortex likely increasingly contributes to the development of jargon babbling, especially around one year of age. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Moreover, just as the pyramidal/corticospinal tracts as well as the somatomotor areas continue to mature and myelinate over the first and second years (Conel, 1937, 1941; Debakan, 2000; Yakovlev and Lecours, 1967) and beyond (Paus et al., 1999), babbling continues throughout the first and second years. It is during these same time periods in which the child gradually acquires and develops the phonetic structure which underlies speech production (de Boysson-Bardies et al. 1981; Oller, 1980; Oller and Lunch, 2012). This implies considerable forebrain as well as right and left neocortical influences over vocal behavior (see below). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">With increasingly neocortical control, what appears to be a "new and unique motor skill" slowly emerges (Moore and Ruark, 1996) which directly contributes to the development of speech. That is, once the neocortical speech area establish hierarchical control, and begin to program the oral-laryngeal motor areas, a new form of (neural-muscular) vocalization emerges which appears somewhat distinct from its precursors (e.g. Moore and Ruark, 1996). The infant begins to speak their first words. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">IMMATURITY OF THE NEOCORTICAL SPEECH AREAS AND JARGON BABBLING <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The overlapping transition from the initial amygdala-brainstem-babbling stage to late babbling, around 4 months of age, may represent the onset of an amygdala to cingulate transition in vocalization control. Around 7-10 months, and as the cingulate become ascendant, the late babbling stage is transformed into the overlapping (cingulate-) canonical babbling stage. Canonical babbling, such as "dadada," involves the rhythmic and repetitive production of identical consonant vowel (CV) syllables (da, ba). Temporal sequencing motor capabilities are the province of the left hemisphere as well as the anterior cingulate gyrus. As the neocortex becomes ascendant and increasingly exercises (albeit immature) motor control, (cingulate-) canonical babblings is followed by (neocortical-) jargon babbling around one year of age. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">The somewhat latter to appear "jargon" (or "conversational") babble resembles actual speech. At a distance it sounds as if the infant were talking, although the infant is in fact spouting prosodically sophisticated nonsense. Jargon babbling appears to reflect the increasing influences of the still exceedingly immature right and left frontal-temporal neocortex. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Jargon babbling is generally produced in a social context and while making eye contact and in many respects is similar if not identical to Wernicke's ("jargon") aphasia. Jargon aphasia is associated with severe injuries to Wernicke's area and the temporal-parietal junction which transmits abnormal streams of neologistic jargon to Broca's area (via the arcuate fasciculus) which then spouts nonsense words; a condition also referred to as "fluent aphasia." However, rather than a function of brain damage, jargon babbling is probably an indication of the extreme immaturity of the superior temporal lobe and Wernicke's area (as well as the left frontal lobe). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In general, "jargon" babbling (like jargon aphasia) consists of normal stress and intonational patterns that have been abnormally sequenced and chunked together. Hence, the infant expresses normal emotional-melodic prosody (probably via the limbic systm and right frontal lobe) coupled with nonsense words (via Broca's area), which makes it sound as if the child is truly attempting to communicate. Indeed, while jargon babbling the infant may appear to be engaging in a two-way discussion, or they may seem to be making requests for help or a desire to direct the other's attention to some object or activity (Kent and Miolo, 1995). Patient's with Wernicke's aphasia behave in an identical fashion. As with Wernicke's aphasics, children who jargon babble are attempting to communicate yet appear oblivious (or agnosic) to the fact they what they are spouting is emotionally meaningful verbal nonsense. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As jargon babbling coincides with the emergence of the infant's first words, this babbling stage heralds a hierarchical shift from the limbic system to the neocortex which increasingly acts to perceive and express social-emotional nuances and to punctuate and impose temporal sequences on what had been purely emotional speech. That is, beginning around 12 months and over the following years, the neocortex of the right hemisphere increasingly subserves the perception and expression of emotional-melodic-prosodic speech--as it does in adulthood (Gorelick and Ross, 1987; Heilman et al. 1975; Lalande et al. 2012; Ross, 1993; Shapiro and Danly, 1985; Tucker et al. 1977). By contrast, the left hemisphere motor areas increasingly act to punctuate, segment, and impose temporal sequences on sound production and perception (Joseph, 1982, 1988a, 1999e). Thus, as the neocortex of the left hemisphere gains motor control over the brainstem and oral musculature, what had been purely limbic language becomes grammatical, vocabulary-rich human speech. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">RIGHT AND LEFT HEMISPHERE LANGUAGE <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">ACQUISITION <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">During the last phase of fetal development the corticospinal tract of the left hemisphere descends and establishes brainstem and spinal synaptic contact in advance of the right (Kertesz and Geschwind, 1971; Yakovlev, and Rakic, 1966). These include pyramidal axons from the left amygdala (and amygdala-striatum), which is more concerned with motor control than the right amygdala, as reflected in its heavier concentrations of dopamine (Bradbury, Costall, Domeney, and Naylor, 1985; Stevens, 2012). Moreover, the left frontal primary motor areas representing the oral-facial and laryngeal muscles and cranial nerves, matures more rapidly than the right frontal primary motor areas (Joseph, 1982; Schiebel, 1991, 1993). In consequence, the left hemisphere is provided with a competitive expressive-motor advantage over the right, which is demonstrated not only in control over the oral-laryngeal musculature, but handedness.



<span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">By contrast, right frontal non-motor and secondary-motor gyral development, and right frontal dendritic growth within the emotional, melodic, prosodic speech area, initially develops faster than Broca's area (Chi et al. 1977; Gilles et al. 2003; Scheibel, 1991, 1993). Although the right hemisphere remains functionally dominant in the non-motor, non-linguistic, sensory-affective modalities (Chiron et al., 1997; Joseph, 1982), neuronatomically, Broca's area overtakes its right-sided counterpart around one year of age (Scheibel, 1991, 1993) and the infant increasingly produces jargon babbling, and then later, its first words. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, due to the earlier development of the right cerebral sensory receptive and non-motor areas, which in turn correspond to the development of the limbic system, sensory-limbic-receptive and expressive emotional functions come to be hierarchically represented in the right half of the brain (Joseph, 1982, 1988a). By contrast, the motoric and associated temporal-sequential aspects of expressive functioning, including right hand dominance, becomes the province of the left hemisphere whose motor areas and corticospinal tract develop more rapidly, which enable it to overtake, and thus gain a competitive advantage over the right. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As the left hemisphere matures and establishes dominance over motor control and expressive speech, temporal sequences and syllabication are imposed on emotional, intonational, and melodic vocalizations which come to be puctuated, segmented, reorganized, classified, and shaped so that vowel, consonantal elements, and words are produced. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Specifically, Broca's expressive speech area, upon receiving linguistic input from the inferior parietal lobule and Wernicke's area (chapter 11) and emotional-prosodic input via the cingulate/medial frontal lobe (Joseph, 1993, 1999e), acts on the adjacent primary and secondary frontal motor areas which subserve the oral-laryngeal musculature (Foerster, 1936; Fox, 1995; LeBlanc, 2012; Petersen, Fox, Posner, Mintum, and Raichle, 1989). In this manner, speech units are motorically organized and vocalized. Thus, left hemisphere speech comes to be superimposed over limbic (and right hemisphere) speech and by one year of age a second form of language emerges, initially one word at a time. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">However, as the left and right frontal and temporal areas interact interhemispherically via the corpus callosum, and intra-hemispherically through the arcuate fasciculus, and as these neocortices are linked with the amygdala and cingulate gyrus, language remains emotional and melodic even as it becomes increasingly grammatical and descriptive. Thus even among adults, language remains emotional, melodic, and prosodic, as these nuances continue to be produced not only by the limbic system, but by the right frontal lobe. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">CONCLUSIONS <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Based on an extensive review of animal and human studies, the preponderance of evidence indicates that the roots of language and social emotional and maternal behavior, originate within the limbic system. Laughter, fear, cries, warning calls, and a variety of emotional vocalizations have been produced via electrode stimulation of wide areas of the limbic system including the hypothalamus, amygdala, cingulate gyrus, and septal nucleus; and these same areas often become activated in response to certain emotional sounds. The limbic system is more vocal than any other part of the brain. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Nevertheless, the type of vocalizations elicited, in general, depends upon which limbic nuclei has been activated. This is because different limbic nuclei, and in fact, different divisions within these nuclei, subserve unique functions and maintain different anatomical interconnections with various regions of the brain. In addition, some areas are more evolutionarily advanced such as the five-layered cingulate gyrus, and/or have expanded and added additional nuclei, such as the lateral amygdala. The vocalizations and emotional behaviors mediated by these recent evolutionary acquisitions are also more complex than those produced by more ancient nuclei such as the medial hypothalamus and brainstem periaqueductal gray. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">In some instances ontogeny replicates phylogeny and over the course of early development the medial hypothalamus (and periaqueductal gray) becomes functionally active and produces primitive vocalizations indicating distress, and later, pleasure. The later to develop medial and lateral amygdala experiences, perceives, and vocalizes joy, wariness, anger, and fear, whereas the neo-limbic cingulate gyrus is capable of producing a wide range of complex social emotional vocalizations such as separation anxiety and those which disguise the individual's true feelings. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As these nuclei and structure interact and mature at different and overlapping rates, over the course of early development the infant's emotional and babbling repertoire expands as does its ability to perceive, vocalize and express social-emotional nuances. The acquisition of infant speech, and the progressive expansion and increased complexity of limbic speech and social emotional behaviors parallels the maturation of these limbic structures. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Likewise, since all humans are in possession of a limbic system which is organized and which develops in a similar manner, the emotional and babbling precursors to language also appear to develop and are expressed in a similar manner regardless of culture. Thus early babbling is associated with the amygdala, late and canonical babbling with the cingulate, and jargon babbling with increasing, albeit immature neocortical influences. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">As the neocortex matures and the amygdala and cingulate gyrus establish interconnections with the superior temporal and frontal lobe, emotional speech and limbic language is slowly transformed into segmented units of prosodic speech and grammatical utterances. That is, the maturing right frontal lobe, via the emotional-melodic speech area, hierarchically comes to express emotional-melodic and prosodic nuances. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">By contrast, the left frontal motor and Broca's expressive speech areas and the left cerebral inferior parietal lobule increasingly punctuate, fractionate, and impose temporal sequences onto the stress, pitch, and melodic intonational contours of the infant's speech output. Hence, vowel, consonantal elements, and then words are produced. Left and right hemisphere speech comes to be superimposed over limbic speech and by one year of age a second form of language emerges, initially one word at a time. <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Although language is commonly associated with the left hemisphere and is discussed in terms of grammar and vocabulary, the underlying foundations are and remain emotional and have their source in the limbic system. It is limbic (and right hemisphere) emotional mediation which explains why patients suffering from severe left hemisphere injury and profound receptive or expressive aphasia retain the capacity to express and comprehend these nuances and the meanings they imply (Boller et al., 2009; Boller and Green, 1982; Joseph, 1982, 1988a; Smith, 1966; Smith and Burklund, 1966). <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">It is due to these same limbic linguistic nuances which enable speakers to convey, and listeners to comprehend, the connotative and contextual implications of what is being said, even when words have been filtered or eliminated (Blumstein and Cooper, 1974; DeUrso, Denes, Testa, and Semenza, 1986; Dwyer and Rinn, 1981; Kramer, 1964), or when interacting with those from other cultures and who speak foreign dialects (Beier and Zautra, 1972; Fernald, 2012; Joseph, 1988a, 1993; Kramer, 1964). Again, consider the famous aside: "I don't know what they're saying, but I sure don't like the sound of it." <span style="background-color: #ffffff; color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 18px; vertical-align: baseline;">Language is both emotional and grammatically descriptive, limbic and neocortical. It is precisely because all humans possess a limbic system which is organized, and which develops in an identical fashion, that a listener is able to comprehend not only the content and grammar of what is said, but the emotion and melody of how it is said --what a speaker feels, even when that speaker is a cooing, gooing, babbling infant.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++