Clinical Neuroanatomy, 28 ed.

The Limbic System

The limbic system subserves basic survival functions that include feeding behavior, “fight-or-flight” responses, aggression, and the expressions of emotion and of the autonomic, behavioral, and endocrine aspects of the sexual response. It includes phylogenetically ancient portions of the cerebral cortex, related subcortical structures, and fiber pathways that connect with the diencephalon and brain stem (Tables 19–1 and 19–2).

TABLE 19–1  Components of the Limbic System and Neocortex.


TABLE 19–2  Major Limbic System Connections.


The limbic system receives input from many parts of the cortex and contains multimodal association areas where various aspects of sensory experience come together to form a single experience. The hippocampus, within the limbic system, plays crucial roles in spatial problem solving and in memory.


The limbic lobe was so named because this cortical complex forms a limbus (border) between the diencephalon and the more lateral neocortex of the telencephalic hemispheres (Fig 19–1). This limbic lobe consists of a ring of cortex outside the corpus callosum, largely made up of the subcallosal and cingulate gyri as well as the parahippocampal gyrus (Fig 19–2).


FIGURE 19–1  Schematic illustration of the location of the limbic system between the diencephalon and the neocortical hemispheres.


FIGURE 19–2  Schematic illustration of the concentric main components of the limbic sytem.

More recent authorities revised the concept of the limbic lobe and refer to the limbic system, which includes the functionally interrelated limbic lobe (parahippocampal, cingulate, and subcallosal gyri), the amygdala, and the hippocampal formation and associated structures (see Table 19–1). The hippocampal formation (a more primitive cortical complex) is situated even closer to the diencephalon and is folded and rolled inward so that it is submerged below the parahippocampal gyrus. The hippocampal formation consists of the hippocampus (Ammon’s horn); the dentate gyrus; the supracallosal gyrus (also termed the indusium griseum), which is the gray matter on top of the corpus callosum; the fornix; and a primitive precommissural area known as the septal area (Fig 19–3).


FIGURE 19–3  Schematic illustration (left oblique view) of the position of the hippocampal formation within the left hemisphere.


The cortical mantle of the brain consists of three concentric cortical regions (hippocampal formation, limbic lobe, and neocortex) with different cytoarchitectonic features (Fig 19–4). The innermost region, the hippocampal formation, is the most primitive, and the outermost, the neocortex the most advanced. The hippocampus, also termed the archicortex, has three layers. The cortex of the transitional limbic lobe—the mesocortex, or juxtallocortex—has as many as five layers. The neocortex, or isocortex, is phylogenetically newest and has five or six layers. It includes the primary motor and sensory cortex as well as the association cortex and covers most of the cerebral hemispheres (see Chapter 10).


FIGURE 19–4  Diagrams of the medial aspect of the right hemisphere in five species. Note the relative increase in size of the human neocortex (isocortex).

The concentric architecture is more obvious in lower species. It is also present in higher species (including humans) and underscores the tiered arrangement of a phylogenetically advanced neocortex, which rests on a more primitive and deeply buried limbic lobe and hippocampal formation. Because of their role in olfaction, the hippocampal formation and limbic lobe were also termed the rhinencephalon (“smell-brain”) by classical neuroanatomists. More recent work has shown that limbic structures are related to the sense of smell but are also directly involved in primitive, affective, visceral, and autonomic functions. Such names as the visceral brain, emotional brain, and limbic brain have been replaced by the more neutral limbic system.


Olfaction (the sense of smell) is phylogenetically one of the oldest senses. The olfactory system constitutes an important input to the limbic system, which is also phylogenetically old.

Olfactory Receptors

The olfactory receptors are specialized neurons located in the olfactory mucous membrane, a portion of the nasal mucosa. The olfactory mucous membrane is blanketed by a thin layer of mucus, produced by Bowman’s glands. The olfactory receptors are highly sensitive and respond with depolarizations when confronted with odor-producing molecules that dissolve in the mucous layer. The olfactory receptors contain, in their membranes, specialized odorant receptors that are coupled to G-protein molecules, which link these receptors to adenylate cyclase. There are nearly 1,000 odorant receptor genes; each olfactory receptor expresses only one or a few (and thus responds to only one or a few odoriferous molecules). When a specific odoriferous molecule binds to the appropriate olfactory receptor, it activates the G-protein molecule, which, via adenylate cyclase, generates cyclic adenosine monophosphate (AMP); this, in turn, leads to opening of Na+ channels, generating a depolarization in the olfactory receptor.

The axons of the olfactory receptors travel within 10 to 15 olfactory nerves to convey the sensation of smell from the nasal mucosa through the cribriform plate to the olfactory bulb (Figs 19–5 and 19–6). The olfactory bulb and olfactory tract (peduncle) lie in the olfactory sulcus on the orbital surface of the frontal lobe. As the tract passes posteriorly, it divides into lateral and medial olfactory striae (Fig 19–7). Within the olfactory bulb, the olfactory receptor axons terminate in specialized synaptic arrangements (termed glomeruli) on the dendrites of mitral cells (see Fig 19–6). Olfactory neurons expressing a specific odorant receptor (and thus responsive to a specific odorant stimulus) project precisely to a small number of glomeruli within the olfactory bulb. There thus appears to be a spatial map within the olfactory bulb that identifies the receptors that have been stimulated.


FIGURE 19–5  The olfactory nerves (lateral view).


FIGURE 19–6  Neural elements in the olfactory bulb.

The mitral cells of the olfactory bulb send their axons posteriorly via the olfactory tracts (also termed the medial and lateral olfactory stria) to the olfactory projection area in the cortex. The lateral olfactory stria is the projection bundle of fibers that passes laterally along the floor of the lateral fissure and enters the olfactory projection area near the uncus in the temporal lobe (see Fig 19–7).


FIGURE 19–7  Olfactory connections projected on the basal aspect of the brain (intermediate olfactory tract not labeled).

The olfactory projection area is the part of the cortex that receives olfactory information. The olfactory projection area includes the pyriform and entorhinal cortex and parts of the amygdala. The pyriform cortex projects, in turn, via the thalamus to the frontal lobe, where conscious discrimination of odors presumably occurs.

The small medial olfactory stria passes medially and up toward the subcallosal gyrus near the inferior part of the corpus callosum. It carries the axons of some mitral cells to the anterior olfactory nucleus, which sends its axons back to the olfactory bulbs on both sides, presumably as part of a feedback circuit that modulates the sensitivity of olfactory sensation. Other olfactory fibers reach the anterior perforated substance, a thin layer of gray matter with many openings that permit the small lenticulostriate arteries to enter the brain; it extends from the olfactory striae to the optic tract. These fibers and the medial stria serve olfactory reflex reactions.


The hippocampal formation is a primitive cortical structure that has been “folded in” and “rolled up” so that it is submerged deep into the parahippocampal gyrus. It consists of the dentate gyrus, the hippocampus, and neighboring subiculum.

The dentate gyrus is a thin, scalloped strip of cortex that lies on the upper surface of the parahippocampal gyrus. The dentate gyrus serves as an input station for the hippocampal formation. It receives inputs from many cortical regions that are relayed to it via the entorhinal cortex, which projects to the dentate gyrus via the perforant pathways. The cells of the dentate gyrus project, in turn, to the hippocampus.

The dentate gyrus is one of the few regions of the mammalian brain where neurogenesis (the production of new neurons) continues through adulthood.


Anosmia, or absence of the sense of smell, is not usually noticed unless it is bilateral. Most commonly, anosmia occurs as a result of nasal infections, including the common cold. Head trauma can produce anosmia as a result of injury to the cribriform plate with damage to the olfactory nerves, bulbs, or tracts. Tumors at the base of the frontal lobe (olfactory groove meningiomas) and frontal lobe gliomas that invade or compress the olfactory bulbs or tracts may cause unilateral or bilateral anosmia. Because damage to the frontal lobes often results in changes in behavior, it is important to carefully examine the sense of smell on both sides when one evaluates any patient with abnormal behavior.

Olfactory information contributes to the sense of flavor. Because of this, patients with anosmia may complain of loss of taste or of the ability to discriminate flavors.

Olfactory hallucinations, also termed uncinate hallucinations, may occur in patients with lesions involving the primary olfactory cortex, uncus, or hippocampus; the patient usually perceives the presence of a pungent, often disagreeable odor. Olfactory hallucinations may be associated with complex partial seizures (uncinate seizures). Their presence should suggest the possibility of focal disease (including mass lesions) in the temporal lobe. An example is provided in Clinical Illustration 19–1.


A 38-year-old composer, who had been previously well, began to have severe headaches and became increasingly irritable. He also began to experience olfactory hallucinations. A colleague noted that “at the end of the second concert . . . he revealed that he had experienced a curious odor of some indefinable burning smell.” Physicians diagnosed a “neurotic disorder,” and he was referred for psychotherapy.

Several months later, a physician noticed papilledema. Several days later, he lapsed into a coma and, despite emergency neurosurgical exploration, died. Postmortem examination revealed a large glioblastoma multiforme in the right temporal lobe.

The patient was George Gershwin. This case illustrates the “George Gershwin syndrome,” in which a hemispheric mass lesion (often a tumor) can remain clinically silent, although it is expanding. Olfactory hallucinations should raise suspicion about a temporal lobe mass. Careful examination of this patient might have provided additional evidence of a mass lesion (eg, an upper homonymous quadrantanopsia; see Chapter 15 and Fig 15–16, lesion D) because of involvement of optic radiation fibers in Meyer’s loop.

The hippocampus (also called Ammon’s horn) extends the length of the floor of the inferior horn of the lateral ventricle and becomes continuous with the fornix below the splenium of the corpus callosum (see Fig 19–3). The name “hippocampus,” which also means “seahorse,” reflects the shape of this structure in coronal section (Fig 19–8). The primitive cortex of the hippocampus is rolled on itself, as seen in coronal sections, in a jelly roll-like manner (Figs 19–9 and 19–10). At early stages in development (and in primitive mammals), the hippocampus is located anteriorly and constitutes part of the outer mantle of the brain (see Fig 19–4). However, in the fully developed human brain, the hippocampus has been displaced inferiorly and medially so that it is hidden beneath the parahippocampal gyrus and is rolled inwardly, accounting for its jelly roll-like structure.


FIGURE 19–8  Micrograph of a coronal section through the medial temporal lobe.


FIGURE 19–9  Schematic illustration of a coronal section showing the components of the hippocampal formation and subiculum. (Compare with Fig 19–8.) CA1 through CA4 are sectors of the hippocampus. Much of the hippocampal input is relayed via the entorhinal cortex from the temporal neocortex.


FIGURE 19–10  Schematic illustration of the major connections to, within, and from the hippocampal formation. (Compare with Fig 19–8.) Dentate granule cells (DG) project to pyramidal neurons in the hippocampus. CA1through CA4 are sectors of the hippocampus.

The hippocampus has been divided into several sectors partly on the basis of fiber connections and partly because pathologic processes, such as ischemia, produce neuronal injury that is most severe in a portion of the hippocampus (H1 [also termed CA1 and CA2], the Sommer sector; see Fig 19–9).

The dentate gyrus and the hippocampus itself show the histologic features of an archicortex with three layers: dendrite, pyramidal cell, and axon. The transitional cortex from the archicortex of the hippocampal to the six-layered neocortex (in this area called the subiculum) is juxtallocortex, or mesocortex, with four or five distinct cortical layers (see Figs 19–8 and 19–9).

Hippocampal input and output have been extensively characterized. The hippocampus receives input from many parts of the neocortex, especially the temporal neocortex. These cortical areas project to the entorhinal cortexwithin the parahippocampal gyrus (see Fig 19–9). From the entorhinal cortex, axons project to the dentate gyrus and hippocampus (Fig 19–11); these axons travel along the perforant pathway and alvear pathways to reach the dentate gyrus and hippocampus (see Fig 19–10).


FIGURE 19–11  Schematic illustration of pathways between the hippocampal formation and the diencephalon. Notice the presence of a loop (Papez circuit), including the parahippocampal gyrus, hippocampus, mamillary bodies, anterior thalamus, and cingulate gyrus. Notice also that the neocortex feeds into this loop.

Within the dentate gyrus and hippocampus, there is an orderly array of synaptic connections (see Fig 19–10). Granule cells of the dentate gyrus send axons (mossy fibers) that terminate on pyramidal neurons in the CA3 region of the hippocampus. These neurons, in turn, project to the fornix, which is a major efferent pathway. Collateral branches (termed Schaffer collaterals) from the CA3 neurons project to the CA1 region.

The fornix is the major outflow tract from the hippocampus. It is an arched white fiber tract extending from the hippocampal formation to the diencephalon and septal area. It carries some incoming axons into the hippocampus and constitutes the major outflow pathway from the hippocampus. Its fibers start as the alveus, a white layer on the ventricular surface of the hippocampus that contains fibers from the dentate gyrus and hippocampus (see Figs 19–8and 19–10). From the alveus, fibers lead to the medial aspect of the hippocampus and form the fimbria of the fornix, a flat band of white fibers that ascends below the splenium of the corpus callosum and bends forward to course above the thalamus, forming the crus (or beginning of the body) of the fornix. The hippocampal commissure, or commissure of the fornix, is a collection of transverse fibers connecting the two crura of the fornix. Many axons in the fornix terminate in the mamillary bodies of the hypothalamus (Fig 19–11). Other axons, traveling in the fornix, terminate in the septal area and anterior thalamus.

The Papez Circuit

As noted earlier, hippocampal efferent axons travel in the fornix and synapse on neurons in the mamillary bodies. These neurons project axons, within the mamillothalamic tract, to the anterior thalamus. The anterior thalamus projects, in turn, to the cingulate gyrus, which contains a bundle of myelinated fibers, the cingulum, that curves around the corpus callosum to reach the parahippocampal gyrus (see Fig 19–11). Thus, the following circuit is formed:

parahippocampal gyrus → hippocampus → fornix mamillary bodies → anterior thalamic nuclei → cingulate gyrus → parahippocampal gyrus

This circuit, called the Papez circuit, ties together the cerebral cortex and the hypothalamus. It provides an anatomic substrate for the convergence of cognitive (cortical) activities, emotional experience, and expression.

A number of cortical structures feed into, or are part of, the Papez circuit. The subcallosal gyrus is the portion of gray matter that covers the inferior aspect of the rostrum of the corpus callosum. It continues posteriorly as the cingulate gyrus and parahippocampal gyrus (see Figs 19–2 and 19–11). In the area of the genu of the corpus callosum, the subcallosal gyrus also contains fibers coursing into the supracallosal gyrus. The supracallosal gyrus (indusium griseum) is a thin layer of gray matter that extends from the subcallosal gyrus and covers the upper surface of the corpus callosum (see Fig 19–11). The medial and lateral longitudinal striae are delicate longitudinal strands that extend along the upper surface of the corpus callosum to and from the hippocampal formation.

Anterior Commissure

The anterior commissure is a band-like tract of white fibers that crosses the midline to join both cerebral hemispheres (see Fig 19–11). It contains two fiber systems: an interbulbar system, which joins both anterior olfactory nuclei near the olfactory bulbs, and an intertemporal system, which connects the temporal lobe areas of both cerebral hemispheres.

Septal Area

The septal area, also called the septal nuclei or septal complex, is an area of gray matter lying above the lamina terminalis and below the rostrum of the corpus callosum, near and around the anterior commissure (Fig 19–12). The septal area is a focal point within the limbic system, and is connected with the olfactory lobe, amygdala, hippocampus, and hypothalamus. The septal area is a “pleasure center” in the brain. Rats with electrodes implanted in the septal area will press a bar repeatedly to receive stimuli in this part of the brain.


FIGURE 19–12  Diagram of the principal connections of the limbic system. A: Hippocampal system and great limbic lobe. B: Olfactory and amygdaloid connections.

A portion of the septal area, the septum lucidum, is a double sheet of gray matter below the genu of the corpus callosum. In humans, the septum separates the anterior portions of the lateral ventricles.

Amygdala and Hypothalamus

The amygdala (amygdaloid nuclear complex) is a gray matter mass that lies in the medial temporal pole between the uncus and the parahippocampal gyrus (Figs 19–12 to 19–14). It is situated just anterior to the tip of the anterior horn of the lateral ventricle. Its fiber connections include the semicircular stria terminalis to the septal area and anterior hypothalamus and a direct amygdalofugal pathway to the middle portion of the hypothalamus (see Fig 19–12). Some fibers of the stria pass across the anterior commissure to the opposite amygdala. The stria terminalis courses along the inferior horn and body of the lateral ventricle to the septal and preoptic areas and the hypothalamus.


FIGURE 19–13  Location of the amygdale (red) within a coronal slice of the brain. (Reproduced, with permission, from Koenigs M, Grafman J: Neuroscientist 2009;15:541.)


FIGURE 19–14  Horizontal section through the head at the level of the midbrain and amygdala. (Reproduced, with permission, from de-Groot J: Correlative Neuroanatomy of Computed Tomography and Magnetic Resonance Imaging.21st ed. Appleton & Lange, 1991.)

Two distinct groups of neurons, the large basolateral nuclear group and the smaller corticomedial nuclear group, can be differentiated. The basolateral nuclear group receives higher order sensory information from association areas in the frontal, temporal, and insular cortex. Axons run back from the amygdala to the association regions of the cortex, suggesting that activity in the amygdala may modulate sensory information processing in the association cortex. The basolateral amygdala is also connected, via the stria terminalis and the amygdalofugal pathway, to the ventral striatum and the thalamus.

The corticomedial nuclear group of the amygdala, located close to the olfactory cortex, is interconnected with it as well as the olfactory bulb. Connections also run, via the stria terminalis and amygdalofugal pathway, to and from the brain stem and hypothalamus.

Functions of the Amygdala

Because of its interconnections with the sensory association cortex and hypothalamus, it has been suggested that the amygdala plays an important role in establishing associations between sensory inputs and various affective states. Activity of neurons within the amygdala is increased during states of apprehension, for example, in response to frightening stimuli. The amygdala also appears to participate in regulating endocrine activity, sexual behavior, and food and water intake, possibly by modulating hypothalamic activity. As described later in this chapter, bilateral damage to the amygdala and neighboring temporal cortex produces the Klüver–Bucy syndrome.

The fornix and medial forebrain bundle, coursing within the hypothalamus, are also considered part of the limbic system.


The limbic system plays a central role in behavior. Experimental studies in both animals and humans indicate that stimulating or damaging some components of the limbic system causes profound changes. Stimulation alters somatic motor responses, leading to bizarre eating and drinking habits, changes in sexual and grooming behavior, and defensive postures of attack and rage. There can be changes in autonomic responses, altering cardiovascular or gastrointestinal function, and in personality, with shifts from passive to aggressive behavior. Damage to some areas of the limbic system may also profoundly affect memory.

Autonomic Nervous System

The hierarchical organization of the autonomic nervous system (see Chapter 20) includes the limbic system; most of the limbic system output connects to the hypothalamus in part via the medial forebrain bundle. The specific sympathetic or parasympathetic aspects of autonomic control are not well localized in the limbic system, however.


The septal area, or complex, is relatively large in such animals as the cat and rat. Because it is a pivotal region with afferent fibers from the olfactory and limbic systems and efferent fibers to the hypothalamus, epithalamus, and midbrain, no single function can be ascribed to the area. Experimental studies have shown the septal area to be a substrate mediating the sensations of pleasure upon self-stimulation or self-reward. Test animals will press a bar repeatedly, to receive a (presumed) pleasurable stimulus in the septal area. Additional areas of pleasure have been found in the hypothalamus and midbrain; the stimulation of yet other areas reportedly evokes the opposite response. Antipsychotic drugs may act in part by modifying dopaminergic inputs from the midbrain to the septal area. An ascending pathway to the septal area may be involved in the euphoric feelings described by narcotic addicts.


Hypothalamic regions associated with typical patterns of behavior such as eating, drinking, sexual behavior, and aggression receive input from the limbic system, especially the amygdaloid and septal complexes. Lesions in these areas can modify, inhibit, or unleash these behaviors. For example, lesions in the lateral amygdala induce unrestrained eating (bulimia), whereas those in the medial amygdala induce anorexia, accompanied by hypersexuality. Electrical stimulation of the amygdala in humans may produce fear, anxiety, or rage and aggression.


Memory involves immediate recall, short-term memory, and long-term memory. The hippocampus is involved in converting short-term memory (up to 60 minutes) to long-term memory (several days or more). The anatomic substrate for long-term memory probably includes the temporal lobes. Patients with bilateral damage to the hippocampus can demonstrate a profound anterograde amnesia, in which no new long-term memories can be established. This lack of memory storage is also present in patients with bilateral interruption of the fornices (eg, by removal of a colloid cyst at the interventricular foramen). Memory processes also involve other structures, including the dorsomedial nuclei of the thalamus and the mamillary bodies of the hypothalamus, as discussed in Chapter 21.

Long-term potentiation, a process whereby synaptic strength is increased when specific efferent inputs to the hippocampus are excited in a paired manner, provides a cellular–molecular basis for understanding the role of the hippocampus in memory and learning.

Place Cells, Grid Cells, and Spatial Problem Solving

In 2014, John O’Keefe received the Nobel Prize for discovering that the hippocampus contains “place cells” that encode spatial memory (“Where have I been?”). Recalling of places, and of the routes required to navigate to them, requires hippocampal activation. Place cells within the hippocampus build, within the brain, an inner map of the environment, and are thus involved in navigation and spatial problem solving.

May-Britt and Edvard Moser extended this work, and shared the 2014 Nobel Prize by showing that the entorhinal cortex, which is the largest input to the hippocampus, contains “grid cells.” The grid cells are arranged in a hexagonal pattern and fire when an animal is in a particular location. Together, the place cells and grid cells provide a GPS system within the brain.

Neurogenesis and Depression

Neurogenesis (the production of new neurosis) continues to occur throughout adulthood in the dentate gyrus. Recent studies have shown a reduced rate of neurogenesis in the dentate gyrus in association with depression. Conversely, antidepressant medications have been shown to increase neurogenesis in the dentate gyrus, and this may contribute to their mechanism of action.

Other Disorders of the Limbic System

A. Klüver–Bucy Syndrome

This disturbance of limbic system activities occurs in patients with bilateral temporal lobe lesions. The major characteristics of this syndrome are hyperorality (a tendency to explore objects by placing them in the mouth together with the indiscriminate eating or chewing of objects and all kinds of food); hypersexuality, sometimes described as a lack of sexual inhibition; psychic blindness, or visual agnosia, in which objects are no longer visually recognized; and personality changes, usually with abnormal passivity or docility. Psychic blindness in the Klüver–Bucy syndrome presumably results from damage to the amydala, which normally functions as a site of transfer of information between sensory association cortex and the hypothalamus. After damage to the amygdala, visual stimuli can no longer be paired with affective (pleasurable or unpleasant) responses.


A 59-year-old man was brought to the hospital because of bizarre behavior for nearly a week. During the prior 2 days he had been confused and had had two shaking “fits.” His wife said that he did not seem to be able to remember things. Twenty-four hours before admission, he had a severe headache, generalized malaise, and a temperature of 101 °F (38.8 °C); he refused to eat. On examination, the patient was lethargic and confused, and had dysphasia. He could only remember one of three objects after 3 minutes. There was no stiffness of the neck. The serum glucose level was 165 mg/dL. Lumbar puncture findings were as follows: pressure, 220 mm H2O; white blood count, 153/µL, mostly lymphocytes; red blood cells, 1450/µL, with xanthochromia; protein, 71 mg/dL; and glucose, 101 mg/dL. An electroencephalogram showed focal slowing over the temporal region on both sides, with sharp periodic bursts. Brain biopsy revealed the features of an active granuloma, without pus formation. A computed tomography scan is shown in Figure 19–15.


FIGURE 19–15  Magnetic resonance image of horizontal section through the head at the level of the temporal lobe. The large lesion in the left temporal lobe and a smaller one on the right side are indicated by arrowheads. Computed tomography scans confirmed the presence of multiple small hemorrhagic lesions in both temporal lobes.

What is the differential diagnosis?

Over the next 8 days, the patient became increasingly drowsy and dysphasic. A repeated scan showed extensive defects of both temporal lobes. The patient died on the 10th day after admission despite appropriate drug treatment.

Cases are discussed further in Chapter 25.

B. Temporal Lobe Epilepsy

The temporal lobe (especially the hippocampus and amygdala) has a lower threshold for epileptic seizure activity than the other cortical areas. Seizures that originate in these regions, called psychomotor (complex partial) seizures, differ from the jacksonian seizures that originate in or near the motor cortex (see Chapter 21). Temporal lobe epilepsy may include abnormal sensations, especially bizarre olfactory sensations, sometimes called uncinate fits; repeated involuntary movements such as chewing, swallowing, and lip smacking; disorders of consciousness; memory loss; hallucinations; and disorders of recall and recognition.

The underlying cause of the seizures may sometimes be difficult to determine. A tumor (eg, astrocytoma or oligodendroglioma) may be responsible, or glial scar formation after trauma to the temporal poles may trigger seizures. Small hamartomas or areas of temporal sclerosis have been found in patients with temporal lobe epilepsy. Although anticonvulsant drugs are often given to control the seizures, they may be ineffective. In these cases, neurosurgical removal of the seizure focus in the temporal lobe may provide excellent seizure control.


Adolphs R: The human amygdala and emotion. Neuroscientist 1999;6:125.

Banasr M, Duman RS. Cell atrophy and loss in depression: reversal by antidepressant treatment. Curr Opin Cell Biol 2011;23:730–738.

Bostock E, Muller RU, Kubie JL: Experience-dependent modifications of hippocampal place cell firing. Hippocampus 1991; 1:193.

Damasio AR: Toward a neurobiology of emotion and feeling. Neuroscientist 1995;1:19.

Dityatev A, Bolshakov V: Amygdala, long-term potentiation, and fear conditioning. Neuroscientist 2005;11:75–88.

Hartley T, Lever C, Burgess N, O’Keefe J: Space in the brain: how the hippocampal formation supports spatial cognition. Phil Trans Roy Soc B 2014; 369:20120510.

Koenigs M, Grafman J: Posttraumatic stress disorder: Role of the medial prefrontal cortex and amygdala. The Neuroscientist 2009;15:540–548.

Levin GR: The amygdala, the hippocampus, and emotional modulation of memory. Neuroscientist 2004;10:31–39.

Macguire EA, Frackowiak SJ, Frith CD: Recalling routes around London: Activation of the right hippocampus in taxi drivers. J Neurosci 1997;17:7103.

McCarthy G: Functional neuroimaging of memory. Neuroscientist 1995;1:155.

Moser EI, Roudi Y, Witter MP, Kentros C, Bonhoeffer T, Moser MB: Grid cells and cortical representation. Nat Rev Neurosci 2014; 15:466–481.

Moulton DG, Beidler LM: Structure and function in the peripheral olfactory system. Physiol Rev 1987;47:1.

O’Keefe J, Nadel L: The Hippocampus as a Cognitive Map. Oxford University Press, 1978.

Reed RR: How does the nose know? Cell 1990;60:1.

Squire LR: Memory and the Brain. Oxford University Press, 1988.

Warren-Schmidt JL, Duman RS. Hippocampal Neurogenesis: Opposing effects of stress and antidepressant treatment. Hippocampus 2006;16:239–249.

Zola-Morgan S, Squire LR: Neuroanatomy of memory. Ann Rev Neurosci 1993;16:547.

BOX 19–1 Essentials for the Clinical Neuroanatomist

After reading and digesting this chapter, you should know and understand:

•  The limbic lobe and limbic system (Tables 19–1 and 19–2)

•  Role in aggression, expression of emotion, autonomic, sexual and appetitive behavior

•  Olfaction: peripheral olfactory receptors and central projections

•  Hippocampal formation (Figs 19–319–919–10, and 19–11)

•  Hippocampus: roles in memory and learning, navigation, spatial problem solving

•  The Papez circuit

•  Septal area and its role as a “pleasure center”

•  Amydala

•  Clinical correlations: Klüver–Bucy syndrome and temporal lobe epilepsy

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