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.
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.
Micrograph of a coronal section through the medial temporal lobe.
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).
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.
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 cortex within 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).
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. CA1 through CA4 are sectors of the hippocampus.
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 19–8 and 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.
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.
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.
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.
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, 19–13, 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.
Location of the amygdale (red) within a coronal slice of the brain. (Reproduced, with permission, from Koenigs M, Grafman J: Neuroscientist 2009;15:541.)
Horizontal section through the head at the level of the midbrain and amygdala. (Reproduced, with permission, from deGroot 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.