These observations in aggregate confirm that integrity of the hippocampal formations and the medial-dorsal nuclei of the thalamus are essential for normal memory and learning. Interestingly, there are only sparse direct anatomic connections between these two regions. The importance assigned to the hippocampal formations and medial thalamic nuclei in memory function does not mean that the mechanisms governing this function are confined to these structures or that these parts of the brain form a “memory center.” It informs us only that these are the sites where the smallest lesions have the most devastating effects on memory and learning. Normal memory function, as emphasized, involves many parts of the brain in addition to diencephalic–hippocampal structures. The aforementioned basal frontal nuclei that project to the hippocampi are an example.
It is also clear that particular lesions of the neocortex may cause impairment of specific forms of memory and learning. Perhaps these high-order cortical functions should not be considered in the same context as what is colloquially called memory because they involve skills that are partly learned but partly innate such as language. Thus, a lesion of the dominant temporal lobe impairs the ability to remember words (loss of explicit semantic memory), and a lesion of the inferior parietal lobule undermines the recognition of written or printed words as well as the ability to relearn them (alexia). The dominant parietal lobe is related to recollection of geometric figures and numbers; the nondominant parietal lobe, to visuospatial relations; the inferoposterior temporal lobes, to the recognition of faces; and the dominant posterofrontal region, to acquiring and remembering motor skills and their affective associations. Whether these are truly forms of memory, or whether these regions of cortex must be entrained in order to retrieve and “experience” the memory, is philosophical. What remains clear is that the integrity of both the hippocampal–thalamic system and the appropriate cortical region is required for memory as we refer to it in this chapter, but only the former is integrated into all modalities of learning and retrieval.
It is a remarkable feature of the Korsakoff amnesic state that no matter how severe the defect in memory may be, it is never complete. Certain past memories can be recalled, but imperfectly and with no regard for their normal temporal relationships, giving them a fictional quality and explaining many instances of confabulation. Another noteworthy fact is that long-standing social habits, automatic motor skills, and memory for words (language) and visual impressions (visual or pictorial attributes of persons, objects, and places) are unimpaired. Long periods of repetition and usage may have made these implicit or procedural memories virtually automatic; they no longer require the participation of the diencephalic–hippocampal structures that were necessary to learn them originally. All of this suggests that these special memories, or coded forms of them, through a process of relearning and habituation, come to be stored or filed in other regions of the brain; that is, they acquire a separate and autonomous anatomy that may be regional, cellular, or subcellular.
Several fundamental questions concerning the amnesic syndrome remain unanswered. Not known is how, or better stated, why a disease process not only impairs future learning but also wipes out portions of a vast reservoir of past memories that had been firmly established before the onset of the illness. Most likely, it is not the memories themselves that are obliterated but the mechanism required to both encode and access them.
One provocative observation regarding memory has been the enhancement of performance by electrical stimulation of the entorhinal area. The study by Suthana and colleagues in individuals with epilepsy is one of several demonstrating this effect as an improved ability to retain topographic-spatial landmarks in a simulated exercise. At a minimum, these findings confirm the role of parahippocampal regions (perforant pathways) in forming and stabilizing memories, in these cases, the major source of afferent input to the hippocampus.