FUNCTIONAL NEUROANATOMY OF THE INFERIOR TEMPORAL LOBES

The entorhinal cortex acts to relays information to and from the hippocampus. It is through the entorhinal cortex that the hippocampus maintains interconnections with the neocortical multi-modal associations areas of the temporal, frontal, and parietal lobes, including surrounding structures, e.g., the parahippocampal gyrus, and allocortical tissues, the perirhinal cortex, septal nuclei and amygdala (Amaral et al. 1992; Carlsen et al. 1982; Gloor, 1955; Krettek & Price, 1976; Murray 1992; Steward, 1977; Van Hoesen et al. 1972). The parahippocampal gyrus, entorhinal and perirhinal cortex, being directly interconnected with the hippocampus and the neocortex, act to relay input from the neocortical association areas to this structure. In fact, they interact so intimately with the hippocampus that some investigators considered them as part of the "hippocampal system." The "hippocampal system" however, is considerd by some to also include the amygdala, dorsal medial nucleus, the septal nuclei, and the hypothalamus and brainstem. Hence, when considered broadly, the "hippocampal" system could be viewed as forming a unified substrate that subserves the non-motor aspects and declarative aspects of memory (Gloor, 1997).

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The entorhinal cortex, particular, is a major component of the "hippocampal system." This structure is truly unique, not only because it serves as an interface between the hippocampus and the neocortex, but because this medial located structures consists of between 7 and 8 layers (Braak & Braak, 1992; Ramon y Cajal, 1902/1955; Rose, 1926). The entorhinal cortex also maintains massive interconnections with all multi-modal neocortical association areas (as well as with the amygdala, hippocampus, septal nuclei, olfactory bulb, etc.) but apparently none of the primary sensory areas (Leichnetz & Astruc, 1976; van Hoesen, et al., 1975). Hence, the entorhinal cortex must play a supramodal role that is exceedingly unique and profoundly important in memory and cognitive processing. However, as to its exact role is difficult to determine, as it is difficult, if not impossible to cut away the entorhinal cortex from the hippocampus without damaging or deinnervating both. Nevertheless, presumably they subserve different aspects of memory.

MEMORY, THE HIPPOCAMPUS & INFERIOR MEDIAL TEMPORAL LOBE

The entorhinal, perirhinal, and parahippocampal neocortex are located in the inferior and medial temporal lobe and are adjacent to and richly interconnected with the hippocampus which is buried within its depths. Like the hippocampus and amygdala, the entorhinal cortices are involved in memory functioning (Gloor, 1990, 1997; Murray, 1992; Nunn et al., 1999; Ploner et al., 1999; Squire, 1992) and may in fact serve as neuronal memory depots that becomes activated during recognition (e.g. Brewer et al., 1998, Wagner et al., 1998).

Over the course of evolution the dorsally situated hippocampus became displaced and progressively assumed a ventral position, during the course of which it also contributed to the neocortical development of the temporal lobe. The amygdala together with the hippocampus, contributed to the evolution of the anterior, medial, superior, and lateral temporal lobes.

Because area 28 like so much of the temporal lobe evolved from these limbic nuclei the hippocampus is enshrouded by the 8 layered Entorhinal Cortex, Area28.

MEMORY

The IT is able to code for and learn new stimuli, can recall the code of the previous stimuli, and can make comparisons between what was perceived on one occasion versus another (Eskandar et al. 1992). This enables IT neurons to make judgments regarding temporal order; if the stimulus was first or second or last (Baylis, & Rolls, 1987; Eskander, et al. 1992). Thus, IT neurons can perform sequential analysis and can compare initial with previous visual representations (Eskandar et al. 1992). Hence, neurons in the IT are involved in form and facial recognition, discrimination, temporal-sequencing, and thus learning and memory for a variety of stimuli.

In addition, IT neurons are directly connected with the entorhinal cortex (Jones & Powel, 1970; Van Hoesen & Pandya, 1975b) -the "gateway to the hippocampus"- as well as to the amygdala (Amaral et al. 1987). Thus neurons located in the inferior temporal lobe are also involved in the maintenance of short term emotional, visual and cognitive memory, and many display heightened activity during delay periods while learning (Fuster & Jevey, 1981; Miyashita & Chang, 1988). Moreover, IT neurons are are also highly concerned with the behavioral context in which learning occurs (Baylis & Rolls, 1987; Gross, et al. 1979; Riches, et al. 1991).

For example, Eskandar, et al. (1992) found in their studies of electrophysiological activity that neurons in the inferior temporal gyrus convey information concerning current versus previous stimulus patterns and their behavioral context. IT neurons are therefore involved in remembering this information, matching it with previously learned information, and are capable of simultaneously transmitting these impressions (including contextual details) to other brain areas. However, IT neurons are also capable of discriminating between stimuli independent of context (Eskandar, et al., 1992).

Hence, IT neurons are involved in both encoding, storage, and recall and interact with the amygdala and hippocampus in regard to learning, memory and recognition. It is in this manner and through these interconnects that IT neurons are involved in emotional as well as non-emotional cognitive processing and memory storage. Conversely, with injuries to the inferior temporal lobe, visual and verbal memory functions suffer (see chapter 14).

THE HIPPOCAMPUS AND ENTORHINAL CORTEX

The hippocampus does not receive direct neocortical input. Moreover, the data it does received, at least from the neocortex, originates in the association areas and is first transmitted to the entorhinal cortex or amygdala, and is then relayed to the hippocampus (see Horel et al. 1987; Issausti et al. 1987; Squire, 1992); the only apparent exception being auditory input which is transfered directly from the primary auditory areas to the entorhinal cortex. It is also via the overlying entorhinal area that the hippocampus receives amygdaloid projections (Carlsen et al., 1982; Gloor, 1955, 1997; Krettek & Price, 1976; Steward, 1977) and fibers from the orbital frontal and temporal lobes (Van Hoesen, et al., 1972). Thus, the hippocampus only receives neocortical input indirectly, and for the most part this is relayed by the entorhinal cortex--the "gateway to the hippocampus."

The entorhinal cortex is truly unique, not only because it serves as an interface between the hippocampus and the neocortex, but because this medial located structure consists of between 7 and 8 layers (Braak & Braak, 1992; Ramon y Cajal, 1902/1955; Rose, 1926). The entorhinal cortex also maintains massive interconnections with all multi-modal neocortical association areas (as well as with the amygdala, hippocampus, septal nuclei, olfactory bulb, etc.) but apparently none of the primary sensory areas (Leichnetz & Astruc, 1976; van Hoesen, et al., 1975). Hence, the entorhinal cortex must play a supramodal role that is exceedingly unique and profoundly important in memory and cognitive processing, and may play different roles, in for example, recognition vs recall vs short term and long-term memory.

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For example, some believe that the neocortex of the temporal lobe is the repository of those long term memories initially processed by the entorhinal cortex and hippocampus and that these latter structures are more important in recognition memory and act to store this material in the neocortex. Consider, for example, patients who undergo "hippocampal removals" whereas the overlying neocortex was spared (Milner, 1990) and patients such as the famous H.M., who underwent bilateral mesial temporal removals: amygdala, hippocampus, entorhinal cortex (Milner, 1968). These patients (particularly those with right sided destruction) perform exceedingly poorly on visual recognition memory tests, including those involving recurring nonsense figures (Kimura, 1963) and human faces (Milner, 1990).

Hence, recognition memory is disrupted with entorhinal and hippocampal removals. However, short term and immediate memory remains intact.

MEMORY, THE HIPPOCAMPUS & ENTORHINA CORTEX

The entorhinal, perirhinal, and parahippocampal neocortex are located in the inferior and medial temporal lobe and are adjacent to and richly interconnected with the hippocampus which is buried within its depths. Like the hippocampus and amygdala, the inferior and medial temporal lobes are involved in memory functioning (Gloor, 1990, 1997; Murray, 1992; Nunn et al., 1999; Ploner et al., 1999; Squire, 1992) and may in fact serve as neuronal memory depots that becomes activated during recognition (e.g. Brewer et al., 1998, Wagner et al., 1998).

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As argued by Heit and colleagues (1990), "MTL firing patterns may contribute to the reactivation of neocortical circuits encoding a particular stimulus-context gestalt" which in turn makes recognition and retrieval possible. For example, the medial temporal lobe (MTL) becomes activated during recognition memory tasks including those involving words and faces (Heit et al. 1990). Indeed, the greater the activation, the greater is the likelihood that material will be remembered (e.g. Brewer et al., 1998; Wagner et al., 1998).

When the inferior and medial temporal lobe is electrically stimulated exceedingly vivid personal memories may be triggered and recalled (Gloor, 1990, 1992, 1997; Halgren 1992; Halgren, et al. 1978; Penfield, 1954; Penfield & Perot, 1963). Patients may report seeing a complex scene from their past or early childhood, including hearing conversations, seeing faces, experiencing somesthetic sensations, and related events. Curiously, however, these scenes do not move forward in time and are otherwise quite static (See Gloor, 1990, 1997; Halgren 1992), like a wide angle, multi-sensory snapshot.

Conversely, left MTL lesions results in recognition deficits for words (Milner & Teuber 1968), whereas those involving the right MTL disrupt memory for visual forms and faces (e.g. Hanley et al. 1990). However, the entorhinal cortex and hippocampus appear to be the crucial structures, whereas the neocortex may be the site where memories are stored. Consider, for example, patients who undergo "hippocampal removals" whereas the overlying neocortex is spared (Milner, 1990) and patients such as the famous H.M., who underwent bilateral mesial temporal removals: amygdala, hippocampus, entorhinal cortex (Milner, 1968). These patients (particularly those with right sided destruction) perform exceedingly poorly on visual recognition memory tests, including those involving recurring nonsense figures (Kimura, 1963) and human faces (Milner, 1990).

In that the inferior and inferior medial temporal lobes also contain neurons which are selectively sensitive to particular sensory features, and will fire in response to faces, hands, and geometric patterns and objects (Gross et al. 1979; Gross et al. 1972; Sergent et al. 1990), it is possible that not only are auditory and visual memories stored within the inferior temporal lobe, but that it may act as an associational warehouse (so to speak) from which particular auditory-visual images can be activated, retrieved and so that comparisons can be made. Through the neocortex the hippocampus and amygdala can gain access to particular perceptual images as well as store associated information via the aid and guidance of the neural circuits maintained in the entorhinal cortex and through which information is transmitted to both nuclei.

For example, the entorhinal cortex acts as a gateway via which information from the immediately adjacent perirhinal cortex (which sits above and is richly interconnected with the amygdala) and the parahippocampal gyrus (which receives visual, auditory and tactual neocortical information) is analyzed and is then transmitted into the hippocampus (see Horel et al. 1987; Issausti et al. 1987; Squire, 1992). It is also via the entorhinal area that the hippocampus receives amygdaloid projections (Carlsen et al., 1982; Gloor, 1955, 1997; Krettek & Price, 1976; Steward, 1977) and fibers from the orbital frontal and temporal lobes (Van Hoesen, et al., 1972). These neocortical regions are thus highly important in memory.

Squire (1992 p. 202) in fact argues that "the cortical structures adjacent to the hippocampus (entorhinal, perirhinal, and parahippocampal cortex) appear to participate with the hippocampus in a common memory function." He bases this argument on his review of numerous studies (many of which were conducted by Squire and Zola Morgan and colleagues) which indicate that severe memory impairments can result from lesions restricted to these cortical areas.

TEMPORAL LOBE INJURIES & MEMORY LOSS

Although a variety of neurochemical and neuroanatomical regions are involved in the formulation of memory, it has long been known that damage or the neurosurgical removal of the temporal lobes can produce profound disturbances in the learning and recollection of verbal and visual stimuli (Milner, 1958; Kimura, 1963; Nunn et al., 1999; Ploner et al., 1999; Squire, 1987, 1992). For example, left temporal lobectomy, siezures or lesions involving the inferior temporal areas can moderately disrupt immediate and severely impair delayed memory for verbal passages, and the recall of verbal paried-associates, consonant trigrams, word lists and number sequences (Delaney et al. 1980; Meyer, 1959; Meyer & Yates,1955; Milner, 1958, 1968; Milner & Teuber, 1968; Weingartner, 1968). Similarly, severe anterograde and retrograde memory loss for verbal material has been noted when the anterior and posterior temporal regions (respectively) are electrically stimulated (Ojeman et al., 1968, 1971).

In contrast, right temporal lesions or lobectomy significantly impair recognition memory for tactile and recurring visual stimuli such as faces and meaningless designs, as well as memory for object position and orientation, and visual-pictorial stimuli (Corkin, 1965; Delaney et al., 1980; Evans et al. 1995; Kimura, 1963; Milner, 1968; Nunn et al., 1999; Ploner et al., 1999; Taylor, 1969). Electrical stimulation of the right anterior and posterior temporal region also causes respectively, severe anterograde and retrograde memory loss for designs and geometric stimuli, and impairs memory for faces Fried et al., 1982; Ojeman et al., 1968).

With bilateral removal of the inferior temporal region there results a condition which has been variably referred to as "psychic blindness" and the "Kluver-Bucy syndrome". However, as explained in chapter 13, this is due to destruction of the amygdala. If the mesial regions are removed, severe memory disturbances involving visual and auditory stimuli result such that the patient suffers a permanent anterograde amnesia, including facial processing impairments (Young et al. 1995).

Based on lesion, temporal lobectomy and electrical stimulation studies it thus appears that the anterior temporal region is more involved in initial consolidation storage phase of memory, whereas the posterior region is more involved in memory retrieval and recall. In addition, as based on event-related functional magnetic imaging (Brewer et al., 1998; Wagner et al., 1999), it appears that the temporal lobes directly interact with the frontal lobes in memorization and remembering. Indeed, the greater the activation of the frontal and temporal lobes (and associated tissues), the greater is the likelihood that subjects will remember whereas reduced activity is associated with forgetting. Hence, these areas interact to promote memory and retention. In consequence, if the frontal lobe is injured, and even if the temporal lobes are spared, patients may demonstrate significant memory loss --due to an inability to correctly search for and find the memory (see chapter 19).

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