While central to memory function, these are not the only regions engaged in the formation and retrieval of memory. A severe but less-enduring defect in memory is observed with damage of the anterior septal gray matter; a cluster of midline nuclei at the base of the frontal lobes, just below the interventricular septum and including the septal nucleus, nucleus accumbens, diagonal band of Broca; and paraventricular hypothalamic gray matter. The case of infarction of this region reported by Phillips and colleagues confirms the participation of this region in memory formation and retrieval. The amnesic syndrome, usually not permanent, that follows a ruptured anterior communicating aneurysm is a consequence of disruption of these nuclei. These septal nuclei have connections with the hippocampus through the precommissural fornix and with the amygdala through the diagonal band. Again, what is most remarkable about this basal frontal amnesic syndrome is its initial severity lasting for weeks to months and the potential for almost complete recovery.
Observations of human disease have confirmed the fundamental importance of the thalamic–hippocampal structures in all memory function. The difficulty of evaluating memory function in monkeys has been overcome to some extent by the use of the “delayed nonmatching-to-sample task,” which is essentially a refined test of recognition memory and is impaired both in patients with the amnesic syndrome and in monkeys with lesions of the mediodorsal nuclei of the thalamus and inferomedial temporal cortical regions (Mishkin and Delacour). Using this method and several others that simulate a restricted form of human amnesia, Zola-Morgan and colleagues have shown that bilateral lesions of the hippocampal formation cause an enduring impairment of memory function. Lesions confined to the fornices or mammillary bodies and stereotaxic lesions of the amygdala that spared the adjacent cortical regions (entorhinal and perirhinal cortices) failed to produce a memory defect. However, lesions that were restricted to the perirhinal and entorhinal cortex (Brodmann areas 35 and 36) and the closely associated parahippocampal cortex did cause a persistent memory defect, presumably by interrupting the major afferent pathways conveying cortical information to the hippocampus. Experimental lesions of the anteromedial parts of the thalamus, which receive and send fibers to the amygdala and hippocampus, similarly abolished memory function.
Regarding specifically thalamic lesions and memory dysfunction in man, a clinical-MRI correlative study by Danet and coworkers demonstrated that isolated infarctions of the left mammillothalamic tract most consistently affected memory, particularly in verbal memory tasks, and isolated lesions of the medial dorsal nucleus of the thalamus caused consistent but less severe memory defects. Thus, the primacy of these two structures in moderate or severe and lasting memory defects is affirmed.
There may be subtle differences in memory disturbance based on the specific location of a lesion in the memory pathways. Graff-Radford and colleagues have found that with purely thalamic lesions, as appreciated by imaging studies, anterograde learning is more affected than retrograde recall; but comparing these functions quantitatively is difficult. Kopelman, in reviewing his own studies and those of others, concludes that the differences are subtle and pertain mostly to temporal ordering and the modality of information, which is degraded more with diencephalic–temporal lesions than with frontal lobe damage.
A body of work using functional neuroimaging also addresses the anatomic mechanisms of memory function. It has been found that the hippocampal formations are consistently engaged during memory acquisition and retrieval tasks. In addition, Maguire’s group found differential activation of the right side during recall of topographic spatial information and the left side for autobiographical memory. Their clever use of London taxi drivers as subjects for imaging studies has further suggested that the volume of the right hippocampus is larger in subjects who have more experience navigating the arcane streets of London. An asymmetrical representation of certain modalities of memory is in keeping with limited clinicopathologic studies of patients who have undergone temporal lobectomy on one side.