The Structures of the Medial Temporal Lobes and their Contribution to Memory Processing
The neuropsychology of human memory has evolved steadily over the last fifty years, and dramatically within the last decade. This essay focuses on the structures of the medial temporal lobes and how they contribute to memory processing. In 1957, the profound effects of bilateral medial temporal lobe resection on memory were described in a patient who became known as H.M. (Scoville & Milner, 1957). This case demonstrated that the medial aspect of the temporal lobe is important for memory function. The successful development of an animal model of H.M.’s memory impairment in the nonhuman primate (Mishkin, 1978; Squire and Zola-Morgan, 1983) led eventually to the identification of the structures that compose the medial temporal lobe memory system: hippocampus, amygdale, parahippocampal cortex, perirhinal cortex and entorhinal cortex (Squire & Zola-Morgan, 1991). (See Appendix 1)
These structures appear to be of great importance for declarative memory consolidation. The hippocampus is a structure deep within the medial temporal lobes. It is implicated in the storage and retrieval of memories for personally experienced events. The hippocampus is a folded structure situated medial to the lateral ventricle. Ventral to the hippocampus are three important cortical regions that surround the rhinal sulclus: the entorhinal cortex, which occupies the medial bank of the rhinal sulcus; the perirhinal cortex, which occupies the lateral bank; and the parahippocampal cortex, which lies lateral to the rhinal sulcus. And finally the amygdale, a structure of the medial temporal lobe that plays a role in memory for the emotional significance of experiences.
During the period of HM (1957) it became apparent that only one kind of memory is impaired following medial temporal lobe damage (Squire, 1992; Schacher and Tulving, 1994; Squire, in press), and that is declarative memory. The importance of medial temporal lobe structures in the acquisition of declarative memory has been appreciated for decades (Corkin, 1984; Milner, Corkin, & Teuber, 1960; Scoville & Milner, 1957). Declarative memory supports the capacity to recollect facts and events, and it supports encoding of memories in terms of relationships among the elements being learned.
There has been a tremendous amount of neuropsychological research centred on amnesic patients with damage to medial temporal lobe structures, which has yielded an enormous amount of information about the organisation of memory (Mayes, 1988; Squire & Butters, 1992; Tulving & Craik, 2000). About 25 years after H.M. was described, the first successes were achieved in establishing an animal model of human amnesia in the monkey (Mishkin, 1978). Cumulative work with the animal model over a 10-year period succeeded in identifying the anatomical components of the medial temporal lobe system (Mishkin & Murray, 1994; Squire & Zola-Morgan, 1991). The success of this effort in monkeys led to similar studies in the rodent, aimed at understanding the contribution of the hippocampus and related structures to memory (Eichenbaum, 1997). Therefore the work done with amnesic patients, monkeys and rodents was the discovery that medial temporal lobe structures are essential for declarative memory.
Each component of the medial temporal lobe contributes differently to memory. One of the most widely studied examples of declarative memory is recognition memory; this refers to the capacity to judge a recently encountered item as familiar. Squire and Zola (1998) found impairments to simple recognition following hippocampal damage. In humans, this point was established in amnesic patients with histologically confirmed damage to the CA1 region of the hippocampus (Reed & Squire, 1997). In monkeys, five studies have assessed the effects of restricted hippocampal lesions made in adulthood on recognition memory performance, as measured by the DNMS task (Zola-Morgan & Squire, 1995). These studies found impaired performance following lesions to the hippocampus. The DNMS task has also been adapted for use with rats (Mumby, Pinel, & Wood, 1990). Several studies have reported that bilateral damage to the hippocampus impairs DNMS performance, (Claik, West, Zola, & Squire, 2001). Nonetheless, one point that should be noted is that removal of the hippocampus also requires removal of the outer neocortex. Hence, further research (Zola-Morgan & Squire, 1995), suggests that the hippocampus appears to be unimportant, as assessed by the DNMS (involving simple recognition). And that damage to the rhinal cortex does impair DNMS; so it can therefore be concluded that although at first it was thought that the hippocampus is the main structure that affects simple recognition, further tests have revealed it is actually the rhinal cortex that plays an important role in simple recognition memory.
Furthermore, studies with animals have provided the opportunity to examine the effects of increasingly selective lesions within the temporal lobe. Aspiration lesions of the hippocampus constantly produced a modest, but significant, DNMS deficit (Murray & Mishkin, 1986). More discrete temporal lobe lesions revealed that the amygdale was not critical (O’Boyle et al. 1993; Zola-Morgan et al. 1989). Lesions involving the rhinal region have since highlighted the importance of the perirhinal cortex (Meunier et al. 1996). These findings have therefore forced a fundamental reappraisal of the contribution of individual temporal structures to memory.
Another view about the division of labour between the hippocampus and the adjacent medial temporal cortex, which is related to the recollection-familiarity distinction, is that the hippocampus might play an especially important role in forming associations between items that are to be learned and that the hippocampus itself is less important for the learning of single items (Henke et al; 1997, 1999; Kroll et al; 1996). In one study (Stark, Bayley, and Squire, 2002), recognition memory was tested for either pictures of houses or faces, on the one hand, or for home-face pairs, on the other hand. For both patients and controls, remembering the pairs was more difficult than remembering single items. However, remembering the pairs was not disproportionately difficult for the patients. Thus, it can be concluded that the hippocampus is more important for associations.
One influential view of hippocampal formation, which grew out of the discovery of hippocampal place cells in the rodent, emphasises its role in the acquisition and retrieval of spatial knowledge (O’Keefe and Nadel, 1978). They claim that the hippocampus plays an important role with respect to spatial memory. By this view, the hippocampus constructs and stores spatial maps and is therefore essential for learning and remembering places, including places learned about long ago.
In view of the finding that hippocampal damage typically produces temporally graded retrograde amnesia (Zola-Morgan & Squire, 1990), the question arises that does the phenomenon of temporarily graded retrograde amnesia extend to spatial memory. This question was addressed in a study of severely amnesic patient E.P. (Teng & Squire, 1999). E.P. was asked to recall the spatial layout of the region where he grew up, and from which he moved away as a young adult more than 50 years previosly. E.P. performed as well as or better than age-matched controls who grew up in the same region and also moved away. The findings show that the medial temporal lobe is not the permanent repository of spatial maps, and they support the view that the hippocampus and other structures in the medial temporal lobe are essential for the formation of long-term memories, both spatial and non-spatial, but not for the retrieval of very remote memories, either spatial or non-spatial.
Further studies (Manns, Hopkins, and Squire, 2003), have looked at patients with hippocampal damage to see whether the hippocampal region is important for semantic knowledge. Findings support the notion that the human hippocampus is important for remembering facts as well as for remembering events. The hippocampal region is important for semantic memory and not just for episodic memory, just as it is important for both recollection and familiarity, and for both conjunction memory and single-item memory (Suzuki, 2003).
Within the medial temporal lobe the perirhinal cortex has also been a focus of study (Murray & Richmond, 2001). Neuronal recording studies provide strong support for the idea of division of function with the medial temporal lobe between the perirhinal and hippocampal cortices. Indeed, electrophysiological evidence of the importance of the perirhinal cortex rather than the hippocampus for judging stimulus familiarity preceded lesion evidence (Brown et al. 1987). A number of studies examined neuronal responses in the perirhinal cortex, during the performance by monkeys of recognition tasks using large sets of stimuli (Brown et al. 1987). The studies confirmed that many neurones in the perirhinal cortex respond maximally to first presentations of visual stimuli, but less to subsequent presentations. Thus, electrophysiological evidence suggests a role for the perirhinal cortex in recoding knowledge concerning individual stimuli.
Although the perirhinal cortex shares many properties with surrounding cortices that also are considered part of the IT cortex, it appears to play an even greater role in mnemonic functions. Lesion studies in monkeys have shown that damage restricted to the perirhinal cortex cause memory impairment, including severe deficits of visual recognition (Gaffan, 1994; Meunier et al, 1993; Zola-Morgan et al, 1993). The findings suggest that the perirhinal cortex, like other medial temporal lobe structures, is most important for the formation of memory and mainly that the rhinal cortex are most important for stimuli.
Affect is also an important dimension for memory-encoding storage and retrieval, and many patients with memory problems have problems in affect as well. One of the structures that stands out against most of the others when it comes to affective information modulation is the amygdala. Damage to the amygdala results in a flattening of emotions. Patients with bilateral amygdala damage may no longer be able to differentiate successfully between relevant and irrelevant information. They consequently fail to successfully encode pertinent new material (Cahill et al, 1995; Markowitsch et al, 1994).
Overall, studies with monkeys and humans have identified the brain structures within the medial temporal lobe that are important for declarative memory. These structures are the hippocampus, the entorhinal cortex, the parahippocampal cortex, and the perirhinal cortex (Squire & Zola, 1996). The amygdale, although critical for aspects of emotional learning (Davis, 1994; LeDoux, 1996) and for the enhancement of declarative memory by emotion (Adolphs et al, 1997), is not critical for declarative memory itself (Zola-Morgan, Squire, and Amaral, 1989).
The findings in this essay describe some of what has been learned recently about the function of the medial temporal lobe. Almost 50 years have passed since the medial temporal lobe was discovered to be important for memory. Since that time, an enormous amount has been learned about the structures within the medial temporal lobe that are important for memory, and about how these structures contribute to memory function. The success of these efforts has been aided by the development of animal models to study both normal memory and memory impairment, and by research focusing on relatively simple tasks such as recognition memory. The greatest success has occurred where it has been possible to move from humans, to monkeys, and even to rodents, using similar concepts and paradigms. It is in these cases that what is being learned about the organisation of memory is most likely to be relevant to the human condition. Hence, it can be concluded that different structures are important for different types of memories.
Then again, the medial temporal lobe is still in the centre of memory research. Questions concern the contributions of individual regions-for example, the hippocampus proper or the entorhinal cortex in information processing; here research with non-human animals is used to unravel the micro circuitry of the kind that patient studies usually cannot provide (Murray, 1996). Furthermore, the role of the hippocampal formation for different subsystems of content-related memory (episodic vs semantic memory) is in dispute (Vargha-Khadem et al., 1997; Tulving & Markowitsch, 1998).
However the debate is still ongoing, different studies bring about different results about the structures of the medial temporal lobes. Therefore important matters for future study include identifying the separate contributions to memory that might be made by the separate anatomical components of the medial temporal lobe system and discovering the mechanism by which memories become independent of medial temporal lobe structures as time passes after learning. These and other questions will benefit from work that combines the study of humans with the study of experimental animals, and from work that explores the same tasks with both lesion analysis and neuroimaging. Conclusively, the major remaining challenge is to clearly characterise the unique psychological and neural processes that each medial lobe structure makes to memory.
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Appendix 1
Structures of the Medial Temporal Lobes
Rhinal Cortex
Perirhinal Parahippocampal
Cortex Cortex
Entorhinal
Cortex
Hippocampus
Amygdala
The Structures of the Medial Temporal Lobes
and their Contribution to Memory Processing