Major Limbic Structures

The limbic lobe refers to cortical areas of the limbic system� These cortical areas, which were given the name “limbic,” form a border (limbus) around the inner structures of the diencephalon and midbrain (see Figure 1�7 and Figure 9�1B)� The core cortical areas include the hippocampal formation, the parahippocampal gyrus, and the cingulate gyrus�

There are a number of cortical areas located in the most medial (also called mesial) aspects of the temporal lobe in humans that form part of this limbus� These areas are collectively called the hippocampal formation; there are three portions-the hippocampus proper, the dentate gyrus, and the subicular region (see Figure 9�3A and Figure 9�3B)� The hippocampus proper is, in fact, no longer found at the surface of the brain, as would be expected for any cortical area� The dentate gyrus is a very small band of cortex, part of which can be found at the surface, and the subicular region is located at the surface but far within the temporal area� These structures are the central structures of the limbic lobe�

The typical cortex of the various lobes of the human brain consists of six layers (and sometimes sublayers), called neocortex� One of the distinguishing features of the limbic cortical areas is that, for the most part, these are older (from an evolutionary perspective) cortical areas consisting of three to five layers, termed allocortex� The hippocampus proper and the dentate cortex are three-layered cortical areas (archicortex), whereas the subicular region has four to five layers (paleocortex)�

Note to the Learner: At this stage, it is very challenging to understand where these structures are located� The component parts of the hippocampal formation are “buried” in the temporal lobe and remain somewhat obscure� It is suggested that the student preview some of the illustrations of the “hippocampus” (see Figure 9�4), as well as sections through the hippocampal formation (see Figure 9�3B) to understand the configuration of the three component parts and the relationship with the parahippocampal gyrus more clearly� The details of these various limbic structures, including their important connections and the functional aspects, are discussed with the appropriate diagram�

The parahippocampal gyrus, which is situated on the inferior aspect of the brain (see Figure  1�5 and Figure 1�6), is a foremost structure of the limbic lobe; it is mostly a five-layered cortical area� It is heavily connected (reciprocally) with the hippocampal formation� The anterior portion of this gyrus is called the entorhinal cortex� This gyrus also has widespread connections with many areas of the cerebral cortex, including all the sensory cortical regions, as well as the cingulate gyrus� It is thought to play a key role in memory function�

The cingulate gyrus, which is situated above the corpus callosum (see Figure 1�7), consists of five-layered cortex, as well as neocortex� The cingulate gyrus is connected reciprocally with the parahippocampal gyrus via by a bundle of fibers in the white matter, known as the cingulum bundle (see Figure 9�1B)� This connection unites the various portions of the limbic “lobe�” It also has widespread connections with the frontal lobe�

Of the many tracts of the limbic system, two major tracts have been included in this diagram-the fornix and the anterior commissure�

• The fornix is one of the more visible tracts and is often encountered during dissections of the brain (e�g�, see Figure 1�7)� This fiber bundle connects the hippocampal formation with other areas (discussed with Figure  9�3A and Figure 9�3B)�

• The anterior commissure is an older commissure than the corpus callosum and connects several structures of the limbic system on the two sides of the brain; these include the amygdala, the hippocampal formation, and parts of the parahippocampal gyrus, as well as the anterior portions of the temporal lobe; the anterior commissure is seen on many of the limbic diagrams and can also be a useful reference point for orientation (e�g�, see Figure 9�6B)�

The other structures shown in this diagram include the diencephalon (the thalamus) and the brainstem� The corpus callosum “area” is indicated as a reference point in these illustrations (see Figure 9�1B)�

This is a dissection of the brain, from the medial perspective (see also Figure 1�7)� The thalamus (diencephalon) has been removed, revealing the fibers of the internal capsule (see Figure 4�4)� The specimen has been tilted slightly to show more of the inferior aspect of the temporal lobe�

The cortex of the cingulate gyrus has been scraped away, revealing a bundle of fibers just below the surface� The dissection is continued to the parahippocampal gyrus, as demarcated by the collateral sulcus or fissure (see Figure 1�5 and Figure 1�6)� This fiber bundle, called the cingulum bundle, is seen to course between these two gyri of the limbic lobe, namely the cingulate gyrus and the parahippocampal gyrus� This association tract is discussed as part of a limbic circuit known as the Papez circuit (discussed with Figure 10�1A)�

The brain is dissected in such a way to reveal the fornix (actually of both sides) as this fiber tract courses from the hippocampal formation in the temporal lobe, courses over the diencephalon, and heads toward its connections (see Figure 9�3A and Figure 9�3B)�

MacLean’s studies indicated that the development of the cingulate gyrus is correlated with the evolution of the mammalian species� He postulated that this gyrus is important for nursing and play behavior, characteristics associated with the rearing of the young in mammals� Included in this behavior is recognizing and responding to the vocalizations of the young (studied in rodents, in cats, and in other animals); a mother responds to the unique tone of her own baby’s crying� This cluster of behavioral patterns forms the

basis of the other “F” in the list of functions of the limbic system, namely, family�

The cingulate gyrus also seems to have an important role in attention, a critical aspect of behavior�

A small cortical region under the anterior part (the rostrum) of the corpus callosum is also included with the limbic system� These small gyri (not labeled; see Figure 1�7) are part of the septal region (see Figure 9�1A) and are considered along with the septal nuclei (see Figure 10�3)�

Other areas of the brain are now known to be involved in limbic functions and are now included in the functional aspects of the limbic system� These areas include large parts of the so-called prefrontal cortex, particularly cortical areas lying above the orbit, the orbitofrontal cortex (not labeled), and the cortex on the medial aspect of the frontal lobe (discussed with Figure 10�1B)�

Deep Brain Stimulation (DBS): In very recent times, a new therapeutic tool has been added-the use of deep brain stimulation� This involves implanting electrodes in very specific areas of the brain and using a small electric current (which can be regulated) to alter some brain functional circuit� The use of this technique in cases of movement disorders (usually Parkinson’s disease) has been well established for a select group of patients�

Deep brain stimulation involving parts of the cingulate gyrus, including an area located anteriorly “below” the corpus callosum, has been used by a few centers for the treatment of profound depression which has not responded to other forms of therapy, as well as some behavioral maladaptive conditions such as obsessivecompulsive disorder� Time will tell if DBS is useful for the alleviation of these conditions, and perhaps others�

The term limbic system is the concept now used to include those parts of the brain that are associated with the functional definition of the limbic system as discussed in the Introduction to this section�

This is an overall diagram focusing on the noncortical components of the limbic system, both core and extended (see Introduction to this section)� These structures are found in the forebrain, the diencephalon, and the midbrain� Each of the structures, including the connections, is discussed in greater detail in subsequent illustrations while this diagram, indicated appropriately, is used to show only the structures of the limbic system that are being described�

The non-cortical structures shown in this diagram include:

• The amygdala�

• The septal region�

• The nucleus accumbens�

• The thalamus�

• The hypothalamus�

• The limbic midbrain�

• The olfactory system�

The amygdala, also called the amygdaloid nucleus, a core limbic structure, is anatomically one of the basal ganglia (as discussed with Figure  2�5A and Figure  2�6)� Functionally, and through its connections, it is part of the limbic system� Therefore, it is considered in this section of the atlas (see Figure 9�6A and Figure 9�6B)�

The septal region includes two components-the cortical gyri below the rostrum of the corpus callosum (see Figure  9�1B) and some nuclei deep to them� These nuclei are not located within the septum pellucidum in the human (see Figure 8�6)� The term septal region includes both the cortical gyri and the nuclei (see Figure 9�1A and Figure 10�3)�

The ventral portions of the striatum and globus pallidus are now known to be connected with limbic functions and are part of the extended limbic system� The nucleus accumbens is located inferior to the neostriatum (specifically, the head of the caudate nucleus; see Figure 2�5B and Figure  2�7)� It has been found to have a critically important function in activities where there is an aspect of reward; this is now thought to be the critical area of

the brain involved in addiction (discussed with Figure 10�7)�

Not represented in this diagram is the region known as the basal forebrain� This subcortical region is composed of several cell groups located beside the hypothalamus and below the anterior commissure (see Figure 10�5A and Figure  10�5B)� This somewhat obscure region has connections with several limbic areas and the prefrontal cortex�

Two of the nuclei of the thalamus, the anterior group of nuclei and the dorsomedial nucleus (see Figure  4�3 and Figure 6�13), are part of the pathways of the limbic system, relaying information from subcortical nuclei to limbic parts of the cortex (the cingulate gyrus and areas of the prefrontal cortex-discussed with Figure  10�1A and Figure 10�1B)�

The hypothalamus lies below and somewhat anterior to the thalamus (see Figure 1�7)� Many nuclei of the hypothalamus function as part of the core limbic system� Only a few of these nuclei are shown, and among these is the prominent mammillary nucleus, which is visible on the inferior view of the brain (see Figure 1�5)� The connection of the hypothalamus to the pituitary gland is not shown�

The extended limbic system also includes nuclei of the midbrain, the so-called limbic midbrain� Some of the descending limbic pathways terminate in this region, and it is important to consider the role of this area in limbic functions� An important limbic pathway, the medial forebrain bundle, interconnects the septal region, the hypothalamus, and the limbic midbrain (see Figure 10�3)� The ventral tegmental area (VTA), now part of the limbic circuitry, is located in the upper midbrain (see Figure 10�6)�

The olfactory system is described with the limbic system because many of its connections are directly with limbic areas� Years ago, it was commonplace to think of various limbic structures as part of the “smell brain,” the rhinencephalon� We now know that this is only partially correct� The olfactory input connects directly into the limbic system (and not via the thalamus; see Figure 10�4), but the limbic system is now known to have many other functional capabilities�

The various tracts which interconnect the limbic structures-fornix, stria terminalis, ventral amygdalofugal pathway-are discussed at the appropriate time with the relevant structure or structures�

This diagram, which is the same as Figure 9�2, highlights the functional portion of the limbic lobe to be discussedthe “hippocampus” (i�e�, the hippocampal formation and the pathway known as the fornix)�

The hippocampal formation includes older cortical regions, all consisting of fewer than six layers, which are located in the medial aspect of the temporal lobe in humans� Much of the difficulty of understanding these structures is their anatomical location deep within the temporal lobe�

In the rat, the hippocampal formation is located dorsally, above the thalamus� During the evolution of the temporal lobe, these structures have migrated into the temporal lobe and have left behind a fiber pathway, the fornix, which is located above the thalamus� (In fact, a vestigial part of the hippocampal formation is still located above the corpus callosum, as shown in this illustrationnot labeled�)

The term hippocampal formation includes the following (see Figure 9�3B):

• The hippocampus proper, a three-layered cortical area that during development becomes “rolled up” and is no longer found at the surface of the hemispheres (as is the case with all other cortical regions)�

• The dentate gyrus, a three-layered cortical area that is partly found on the surface of the brain, although its location is so deep that it presents a challenge to non-experts to locate and visualize this thin ridge of cortex�

• The subicular region, a transitional cortical area of three to five layers that becomes continuous with the parahippocampal gyrus (located on the inferior aspect of the brain; see Figure 1�5)�

The fornix is a fiber bundle that is visible on medial views of the brain (at the lower edge of the septum pellucidum) (see Figure 1�7)� These fibers emerge from the hippocampal formation (shown in Figure  9�4; see also Figure 9�1B) and course over the thalamus, where they are found just below the corpus callosum (see coronal sections; Figure 2�9A and Figure 9�5A)� The fibers end in the septal region and in the mammillary nucleus of the

hypothalamus (shown in Figure 9�3B)� Some fibers in the fornix are conveying information from these regions to the hippocampal formation� It is perhaps best to regard the fornix as an association bundle, part of the limbic pathways� It has attracted much attention because of its connections and because of its visibility and accessibility for research into the function of the hippocampal formation, particularly with regard to memory�

Studies in animals have indicated that the neurons located in one portion of the hippocampus proper, called the CA3 region, are critical for the formation of new memoriesdeclarative or episodic types of memories (not procedural)� This means that in order for the brain to “remember” some new fact or event, the new information must be “recorded” or registered within the hippocampal formation� This information is “processed” through some complex circuitry in these structures and is retained for a brief period of seconds� For it to be remembered for longer periods, some partially understood process occurs so that the transient memory trace is transferred to other parts of the brain, and this is now stored in working memory or as a long-term memory� (An analogy to computers may be useful here: if a document is not saved, it is not available for use-ever again�) The process of memory storage may require a period of hours, if not days�

In the study of the function of the hippocampus in animals, there is considerable evidence that the hippocampal formation is involved in constructing a “spatial map�” According to this literature, this part of the brain is needed to orient in a complex environment (e�g�, a maze)� It is not quite clear whether this is a memory function or whether this spatial representation depends on the connections of the hippocampal formation and parahippocampal gyrus with other parts of the brain�

The clinical implications of the functional involvement of the hippocampal formation in memory are further elaborated with Figure 9�4�

It is now possible to view the hippocampal area in detail on magnetic resonance imaging scans (MRI) and to assess the volume of tissue (see Figure 9�5B)� Bilateral damage here apparently correlates with the loss of memory function in humans with Alzheimer’s dementia, particularly for the formation of memories for new events or for new information (further discussed with Figure 9�4)�

The hippocampal formation is one of the most important components of the limbic system in humans� It is certainly the most complex� This diagram isolates the component parts of the hippocampal formation, on both sides�

One expects a cortical area to be found at the surface of the brain, even if this surface is located deep within a fissure� During the evolution and development of the hippocampal formation, these areas became “rolled up” within the brain� Of the three, the hippocampus proper is found completely “within the brain�”

Note to the Learner: The student is advised to consult Functional Neuroanatomy of Man, by Williams and Warwick (see the Annotated Bibliography), for a detailed visualization and understanding of this developmental phenomenon�

The hippocampus proper consists of a three-layered cortical area� This forms a large mass, which actually intrudes into the ventricular space of the inferior horn of the lateral ventricle (see Figure 7�5 and Figure 9�5A)� In a coronal section through this region, there is a certain resemblance of the hippocampal structures to the shape of a seahorse (see Figure 9�5A)� From this shape, the name “hippocampus” is derived, from the French word for seahorse� The other name for this area is Ammon’s horn or cornu ammonis (abbreviated CA), named after an Egyptian deity with ram’s horns because of the curvature of the hippocampus in the brain� This cortical region has been divided into a number of subportions (CA1 to CA4, usually studied in more advanced courses)�

The dentate gyrus is also a phylogenetically older cortical area consisting of only three layers� During the formation discussed earlier, the leading edge of the cortex detaches itself and becomes the dentate gyrus� Parts of it remain visible at the surface of the brain�

Because this small surface is buried on the most medial aspect of the temporal lobe and is located deep within a fissure, it is rarely located in studies of the gross brain� Its cortical surface has serrations, which led to its name dentate (referring to teeth; (see also Figure 9�7))�

The appearance of the dentate gyrus is shown on the view of the medial aspect of the temporal lobe (on the far

side of the illustration)� A “cut” section through the temporal lobe (as seen in the lower portion of this illustration) indicates that the dentate gyrus is more extensive than its exposed surface portion�

The next part of the cortically rolled-in structures that make up the hippocampal formation is the subicular region� The cortical thickness is transitional, starting from the three-layered hippocampal formation to the more layered parahippocampal gyrus (see also Figure 1�5)� (Again, there are a number of subparts of this area that are rarely studied in an introductory course�)

In the temporal lobe, the hippocampal formation is adjacent to the six-layered parahippocampal gyrus, with which it has extensive reciprocal connections� The hippocampal formation also receives input from the amygdala� There are extensive interconnections within the component parts of the hippocampal formation itself�

Part of the output of this cortical region is directed back toward the parahippocampal gyrus, which itself has extensive connections with other cortical areas of the brain, particularly sensory areas� This is analogous to the cortical association pathways described earlier�

The other major output of the hippocampal formation is through the fornix (see also Figure 9�4)� Only the hippocampus proper and the subicular region project fibers into the fornix� This can be regarded as a subcortical pathway that terminates in the septal region (via the precommissural fibers; discussed with Figure 10�3) and in the mammillary nucleus of the hypothalamus (via the postcommissural fibers; discussed with Figure  10�2)� There are also connections in the fornix from the septal region back to the hippocampal formation� The dentate gyrus connects only with other parts of the hippocampal formation and does not project beyond it�

The term medial or mesial temporal sclerosis is a general term for damage to the hippocampal region located in this part of the brain� Lesions in this area are known to be associated with epilepsy, particularly psychomotor seizures, classified as a partial complex seizure disorder�

MRI imaging is very useful for the diagnosis of mesial temporal sclerosis� Provided that the hippocampus on the other side is functioning (discussed with Figure 9�4), surgical removal of the anterior temporal region may be recommended, in select cases, to alleviate the epileptic condition when anti-epileptic medication has not been successful�

The brain is being shown from the lateral aspect (as in Figure 1�3 and Figure 1�4)� The left hemisphere has been dissected by removing cortex and white matter above the corpus callosum: the lateral ventricle has been exposed from this perspective (see Figure 2�1A)� The choroid plexus tissue has been removed from the ventricle to improve visualization of the structures� This dissection also shows the lateral aspect of the lentiform nucleus, the putamen, and the fibers of the internal capsule between it  and the thalamus (see Figure 1�7, Figure 2�10A, and Figure 2�10B)�

A similar dissection has been performed in the temporal lobe, thereby exposing the inferior horn of the lateral ventricle (see Figure 2�8)� A large mass of tissue is found protruding into the inferior horn of this ventricle-named the hippocampus, a visible gross brain structure� In fact, the correct term now used is the hippocampal formation� In a coronal section through this region, the protrusion of the hippocampus into the inferior horn of the lateral ventricle can also be seen, almost obliterating the ventricular space (shown in Figure  9�5A; see also Figure  2�9A and Figure 2�9B)� An unusual view of the hippocampal formation-from above-is seen in Figure 7�6 (particularly well seen on the right side of the illustration)�

The hippocampal formation is composed of three distinct regions-the hippocampus proper (Ammon’s horn), the dentate gyrus, and the subicular region, as explained with Figure 9�3B� The fiber bundle that arises from the visible “hippocampus,” the fornix, can be seen adjacent to the hippocampus in the temporal lobe (see Figure  9�1A and Figure 9�1B), and it continues over the top of the thalamus (discussed with Figure 9�3B; see also Figure 1�7)�

The T1 MRI (magnetic resonance imaging scan)—from the same perspective-captures the whole lateral ventricle and the hippocampal formation in the inferior horn in the temporal lobe, as well as structures in the “core” (the putamen of the lentiform nucleus and fibers of the internal capsule)� Note the choroid plexus in the atrium of the lateral ventricle (also seen in Figure 6�5)�

It is now known that the hippocampal formation is the critical structure for memory� This function of the hippocampal formation became understood because of an individual known in the literature as H�M�—Henry Molaison (1926-2008)� H�M� suffered from intractable epilepsy (that may have been caused by a bicycle accident at the age of 7)� In 1953, at the age of 27, he had neurosurgery to alleviate his condition (which it did) consisting of bilateral medial temporal lobe resection, including most of the hippocampal formation and adjacent structures�

After the surgery it was found that H�M� could not form new memories for facts or events (episodic memory, also called explicit memory), although subsequent studies found that he could learn new motor skills (called implicit or procedural memory)�

Our understanding of memory, the different types of memory, and the role of the hippocampal formation in the formation of new memories for facts or events was formulated from the studies of H�M� by Dr� Brenda Milner, a well known Canadian neuropsychologist (who later moved to the Montreal Neurological Institute, the MNI, and worked with the world-famous neurosurgeon Dr� Wilder Penfield)�

We now know that bilateral damage or removal of the anterior temporal lobe structures, including the amygdala and the hippocampal formation, leads to a unique condition in which the person can no longer form new declarative or episodic memories, although older memories are intact� The individual cannot remember what occurred moments before� Therefore, the individual is unable to learn (i�e�, to acquire new information) and is not able to function independently�

In order to determine the functionality of the hippocampus, a test called the Wada Test was devised� This involves injecting a short acting barbiturate into each carotid artery and observing its effect on speech and short term memory on each half of the brain� This test has been supplemented with the availability of functional MRI (fMRI)�

If a surgical procedure is to be performed in this region nowadays, additional special neuropsychological testing must be done to ascertain that the hippocampus contralateral to the operation is intact and functioning�

Note to the Learner: It is suggested that the learner read further about memory, H�M� and other similar cases in the neuropsychology literature (see Annotated Bibliography)�

This section is taken posterior to the one shown in Figure  2�9A (see upper left image), and it includes the inferior horn of the lateral ventricle (see Figure 2�8 and Figure 9�4)� The basal ganglia, putamen, and globus pallidus are no longer present (see Figure 2�10A)� The corpus callosum is seen in the depth of the interhemispheric fissure, and at this plane of section the fornix is found just below the corpus callosum (see Figure 1�7)� The thalamus is below� The section includes the body of the lateral ventricle (see Figure 2�1A), and choroid plexus is seen on its medial corner (see Figure 7�8)� The body of the caudate nucleus is adjacent to the body of the lateral ventricle� The section passes through the midbrain (with the red nucleus and the substantia nigra) and the pons, as shown in the upper right image�

The inferior horn of the lateral ventricles (shown at higher magnification in the lower inset) is found in the temporal lobes on both sides and is seen as only a small crescent-shaped cavity (shown also in Figure  6�2)� The inferior horn of the lateral ventricle is reduced to a narrow slit because a mass of tissue protrudes into this part of the ventricle from its medial-inferior aspect� Closer inspection of this tissue reveals that it is gray matter; this gray matter is in fact the hippocampus proper�

This plane of viewing (shown more clearly in the enlarged view below) allows one to follow the gray matter from the hippocampus proper medially and through an intermediate zone, known as the subiculum or subicular region (see Figure 9�3B), until it becomes continuous with the gray matter of the parahippocampal gyrus� The hippocampus proper has only three cortical layers� The subicular region consists of four to five layers; the parahippocampal gyrus is to a large part a five-layered cortex� This view also allows us to understand that the parahippocampal gyrus is so named because it lies beside the “hippocampus�”

The neurons of the hippocampal area are prone to damage for a variety of reasons, including vascular conditions� The key neurons for memory function are located in the hippocampus proper, and these neurons are extremely sensitive to anoxic states� An acute hypoxic event, such as occurs in cardiac arrest, is thought to trigger delayed death of these neurons, several days later, termed apoptosis, programmed cell death� Much research is now in progress to try to understand this cellular phenomenon and to devise methods to stop this reaction of these neurons�

Currently, studies indicate that in certain forms of dementia, particularly Alzheimer’s dementia (AD), there is a selective loss of neurons in this same region of the hippocampus proper� This loss is caused by involvement of these neurons in the disease process� Again, this correlates with the type of memory deficit seen in this condition-loss of short-term memory-although the disease clearly involves other neocortical areas, which goes along with the other cognitive deficits typical for this disease�

We now know, based on extensive research, that new neurons are generated in the adult human brain in the dentate gyrus, and some of these new neurons survive and become incorporated into the brain circuitry� Much research is under way looking at ways to enhance this process and how to induce a similar “replacement program” in other brain areas, particularly following injury and strokes�

Note to the Learner: The only other area where new neurons are generated in the adult human brain is the olfactory system� Adult human neurogenesis is further discussed with Figure 9�5B�

The relationship of the caudate nucleus with the lateral ventricle is shown in two locations-with the body of the ventricle and with the tail in the “roof” of the inferior horn (see Figure 2�5B and Figure 2�7)�

This coronal image of the brain is taken particularly to view the medial aspect of the temporal lobe as part of a “seizure protocol” (because of the known association between lesions of the medial, also called mesial, temporal lobe and seizures)�

The plane of view indicated in the locator image above includes the frontal lobe with the anterior horn of the lateral ventricles separated by the septum� Note the connection between the lateral ventricles and the 3rd ventricle-the foramen of Monro, on both sides (see Figure 7�8)�

With this view, the hippocampal formation is seen infringing on the space of the inferior horn of the lateral ventricle in the temporal lobe (see Figure  9�4 and Figure 9�5A)�

This image can be used to “quantify” the volume of the hippocampal formation, by noting especially whether there is a reduction in the size of the hippocampus in patients being investigated for memory loss and dementia� This volumetric quantification is still not-as yet-used as a diagnostic criterion for Alzheimer’s dementia�

In this view, it appears as if the fibers of the internal capsule are continuing into the midbrain which in fact they do, forming the cerebral peduncle (see Figure 4�4 and Figure 5�15 and also Figure 9�5A)� The outline of the pons is recognizable, as is the narrower medulla�

Additional note: It is now known that neurogenesisnew neurons-are generated in adult humans, throughout life, although diminishing with age� There is accumulating evidence that certain adult lifestyle modifications, mainly physical exercise, may lead to an enhancement of this process� The implications of these findings are an active area of current research, particularly for those usually older individuals with minimal cognitive impairment (MCI), or those afflicted with dementia of the Alzheimer type (AD)�

This diagram, which is the same one as Figure 9�2, highlights a functional portion of the limbic system-the amygdala and its pathways, the stria terminalis and the ventral amygdalofugal pathway� The septal region (nuclei) is also included�

The amygdala (amygdaloid nucleus) is a subcortical nuclear structure located in the temporal lobe in humans (see Figure 2�5A and Figure 2�5)� As a subcortical nucleus of the forebrain, it belongs by definition with the basal ganglia, but because its connections are with limbic structures, it is now almost always described with the limbic system�

The amygdala is located between the temporal pole (the most anterior tip of the temporal lobe) and the end of the inferior horn of the lateral ventricle (in the temporal lobe; see Figure 2�1A)� The nucleus is located “inside” the uncus, which is seen on the inferior aspect of the brain as a large medial protrusion of the anterior aspect of the temporal lobe (see Figure 1�5 and Figure 1�6)�

The amygdala receives input from the olfactory system, as well as from visceral structures� Two fiber tracts are  shown connecting the amygdala to other limbic structures-a dorsal tract (the stria terminalis) and a ventral tract (the ventral amygdalofugal pathway, consisting of two parts)� These are described in detail with Figure 9�6B�

The amygdala in humans is now being shown, using functional magnetic resonance imaging (fMRI), to be the area of the brain that is best correlated with emotional reactions, often associated with fearful situations� The emotional aspect of the response of the individual is passed onto the frontal cortex (discussed with the connections in Figure 9�6B), where “decisions” are made regarding possible responses� In this way, the response of the individual incorporates the emotional aspect of the situation�

Stimulation of the amygdaloid nucleus produces a variety of vegetative responses, including licking and chewing movements� Functionally, in animal experimentation, stimulation of the amygdala may produce a rage response, whereas removal of the amygdala (bilaterally) results in docility� Similar responses are also seen with stimulation or lesions in the hypothalamus� Some of these responses may occur through nuclei in the midbrain and medulla�

In monkeys, bilateral removal of the anterior parts of the temporal lobe (including the amygdala) produces

some behavioral effects that are collectively called the Kluver-Bucy syndrome� The monkeys evidently become tamer after the surgical procedure, put everything into their mouths, and display inappropriate sexual behavior�

The amygdala is also known to contain a high amount of enkephalins� It is not clear why this is so and what may be the functional significance�

The MRI scans in the lower part of the illustration, taken from two perspectives as indicated in the small illustrations, show the nuclear structure, the amygdala, in the temporal lobe� The image on the left in the horizontal (axial) plane is a T2-weighted image, and the amygdala is seen occupying the temporal “pole�” The image on the right in the coronal plane is a FLAIR (fluid attenuation inversion recovery) image, and the amygdala is seen just as the inferior horn of the lateral ventricle is disappearing, at its very anterior end; on the right side of the image, the amygdala is located under the protruding tissue mass called the uncus (see Figure 1�5 and Figure 1�6)� In fact, it is the amygdala nucleus that forms the uncus�

The amygdala is known to have a low threshold for electrical discharges, and this may make it prone to be the focus for the development of seizures� This has been found to occur in kindling, an experimental model of epilepsy� In humans, epilepsy from this part of the brain (anterior and medial temporal regions) usually gives rise to complex partial seizures, sometimes called temporal lobe seizures, in which automatisms such as lip smacking movements and fumbling of the hands are often seen, along with transient cognitive impairment (see also Figure 9�3B)�

In very rare circumstances, bilateral destruction of the amygdala is recommended in humans for individuals whose violent behavior cannot be controlled by other means� This type of treatment is called psychosurgery�

The role of the amygdala in the formation of memory is not clear� Bilateral removal of the anterior portions of the temporal lobe in humans for the treatment of severe cases of epilepsy results in a memory disorder, which has been described with the hippocampal formation (discussed with Figure 9�4 and Figure 9�5A)� It is possible that the role of the amygdala in the formation of memories is mediated either through the connections of this nuclear complex with the hippocampus or with the dorsomedial nucleus of the thalamus (see Figure 10�1B)�

One of the major differences between the amygdala and the other parts of the basal ganglia is that the amygdala is not a homogeneous nuclear structure but is composed in fact of different component parts� These parts are not usually studied in an introductory course�

The amygdala receives a variety of inputs from other parts of the brain, including the adjacent parahippocampal gyrus (not illustrated)� It receives olfactory input directly (via the lateral olfactory stria; see Figure  10�4) and indirectly (from the cortex of the uncal region, as shown on the left side of the diagram)�

The amygdaloid nuclei are connected to the hypothalamus, the thalamus (mainly the dorsomedial nucleus), and the septal region� The connections, which are reciprocal, travel through two routes:

• A dorsal route, known as the stria terminalis, which follows the ventricular curve and is found on the upper aspect of the thalamus (see Figure 9�6A)� The stria terminalis lies adjacent to the body of the caudate nucleus in this location� This connects the amygdala with the hypothalamus and the septal region�

• A ventral route, known as the ventral pathway or the ventral amygdalofugal pathway� This pathway, which goes through the basal forebrain region (see Figure  10�5A), connects the amygdala to the hypothalamus (as shown) and to the thalamus (the fibers are shown en route), particularly the dorsomedial nucleus (see Figure 6�13 and Figure 10�1B)�

The connection with the hypothalamus is likely the basis for the similarity of responses seen in animals with

stimulation of the amygdala and the hypothalamus (see Figure 9�6A and Figure 10�2)� This pathway to the hypothalamus may result in endocrine responses, and the connections with the midbrain and medulla may lead to autonomic response (see Figure 10�2)�

Further possible connections of the amygdala with other limbic structures and other parts of the brain can occur via the septal region (see Figure 10�3), as well as via the dorsomedial nucleus of the thalamus to the prefrontal cortex (see Figure 10�1B)�

The anterior commissure conveys connections between the nuclei of the two sides�

Seizure activity in the anterior temporal region may spread to the orbitofrontal region, via a particular group of fibers called the uncinate bundle (see Additional Detail below)�

There is a white matter association pathway between the anterior pole of the temporal lobe and the inferior (orbital) part of the frontal lobe called the uncinate fasciculus, a “U-shaped” bundle of fibers� It is suggested that the student consult other texts for an illustration of this structure (see the Annotated Bibliography-for example, Figure 22-9 in The Human Brain, by Nolte 6th edition; a clearer image of a dissection of the uncinate fascicullus is seen in Nolte’s 5th edition, Figure 22-11)� The role of this pathway in the epileptic condition unfortunately named “uncinate fits” is discussed with Figure 10�4� The role of the orbital and medial parts of the frontal lobe as part of the limbic system is discussed with Figure 10�8 (see also Figure 6�13) and under “synthesis” at the end of the Limbic section�

The temporal lobe is a more recent addition in the evolution of the hemispheres, and it develops later in the formation of the brain� During the development of the temporal lobe, certain structures migrate into it-the lateral ventricle, the hippocampal formation, and the caudate nucleus, as well as various tracts, the fornix, and the stria terminalis�

The lateral ventricle and associated structures form a crescent in the shape of a reverse letter “C” (see Figure 2�1A)� These relationships are shown in this diagram by detailed “cuts” at various points along the lateral ventricle:

• The first section is through the anterior (frontal) horn of the ventricle, in front of the interventricular foramen (of Monro)�

• The following section is through the body of the ventricle, over the dorsal aspect of the thalamus�

• The next section shows the ventricle at its curvature into the temporal lobe (this area is called the atrium or the trigone)�

• The last section is through the inferior horn of the ventricle, in the temporal lobe, including the hippocampal formation�

Note to the Learner: The initials used in the sections (insets) to identify structures are found in parentheses after the labeled structure in the main part of the diagram�

The various parts of the caudate nucleus-the head, the body, and the tail-follow the inner curvature of the lateral ventricle (see Figure 2�5A)� The large head is found in relation to the anterior horn of the lateral ventricle, where it bulges into the space of the ventricle (see Figure 2�9A and Figure  2�10A)� The body of the caudate nucleus is coincident with the body of the lateral ventricle, on its lateral aspect (see Figure 2�9A and Figure 9�5A)� As the caudate follows the ventricle into the temporal lobe, it becomes the tail of the caudate nucleus, where it is found on the upper aspect of the inferior horn, its roof (see Figure 6�2 and Figure 9�5A)�

The hippocampal formation is found in the temporal lobe situated medial and inferior to the ventricle (see Figure 9�3A, Figure 9�3B, and Figure 9�4)� It bulges into the ventricle, almost obliterating the space; it is often difficult to visualize the small crevice of the ventricle in specimens and radiograms� The dentate gyrus is again seen (on the far side) with its indented surface (see also Figure 9�3B)� The configuration of the three parts of the hippocampal formation is shown in the lower section�

The fornix is easily found in studies of the gross brain (e�g�, see Figure 1�7)� Its fibers can be seen as a continuation of the hippocampal formation (see Figure 9�3B and Figure 9�4), and these fibers course on the inner aspect of the ventricle as they sweep forward above the thalamus� In the area above the thalamus and below the corpus callosum (see coronal section; Figure  2�9A), the fornix is found at the lower edge of the septum pellucidum� Here, the fornix of one side is in fact adjacent to that of the other side (see also Figure 9�2); there are some interconnections between the two sides in this area�

The fibers of the fornix pass in front of the interventricular foramen (see medial view of brain in Figure 1�7)� They then divide into pre-commissural (referring to the anterior commissure) fibers to the septal region (see Figure 9�3A, Figure 9�3B, and Figure 10�3) and post-commissural fibers, through the hypothalamus, to the mammillary nucleus (which is not portrayed in this diagram; see Figure  1�5 and Figure  1�6, as well as Figure  9�3B and Figure 10�3; also Figure 10�1A)�

The amygdala is clearly seen to be situated anterior to the inferior horn of the lateral ventricle and in front of the hippocampal formation (see Figure 2�5A and Figure 9�6A)�

The stria terminalis follows essentially the same course as the fornix (see Figure 9�2), by connecting the amygdala with septal region and hypothalamus (see Figure 10�3)�

The stria terminalis is found slightly more medially on the dorsal aspect of the thalamus, in the floor of the body of the lateral ventricle� In the temporal lobe, the stria is found in the roof of the inferior horn of the lateral ventricle�