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Maguire s group has found a 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 (Maguire et al) This asymmetric representation of certain modalities of memory is in keeping with limited clinicopathologic studies of patients who have undergone temporal lobectomy on one side These observations in aggregate indicate that integrity of the hippocampal formations and the mediodorsal 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 con ned 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 extensive lesions of the neocortex may cause impairment of retentive memory and learning and that this effect is probably more dependent upon the size of the lesion than upon its locus Of particular importance are the circumscribed areas of the cerebral cortex related to special forms of learning and memory (so-called modality-based memory), a subject that is considered in detail in the next chapter 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 gures 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 semantic Taken to its extremes, aphasia from a left temporal perisylvian lesion (Wernicke aphasia) could be viewed as an amnesia for language, and parietal lesions that cause ideomotor apraxia could be taken to represent a loss of memory for these previously learned acts What remains clear is that the integrity of both the hippocampal-thalamic system and the appropriate cortical region is required for memory as it is commonly understood, but only the former is integrated into all modalities of learning and retrieval Any hypothesis concerning the anatomic substratum of learning and retentive memory must therefore include not only the diencephalic-hippocampal structures but also special parts of the neocortex and midbrain reticular formation (for maintaining alertness) We would suggest that the diencephalic-hippocampal structures are involved in all active phases of learning and integration of new information, regardless of the sense avenue through which this information reaches the organism or of the nal pathway of its expression, and it seems to make little difference whether the newly acquired information involves functions classed as purely cognitive or as emotional It is a remarkable feature of the Korsakoff amnesic state that no matter how severe the defect in retentive memory may be, it is never complete Certain past memories can be recalled, but.

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Table 21-5 Classi cation of the amnesic states I Amnesic syndrome of sudden onset usually with gradual but incomplete recovery A Bilateral or left (dominant) hippocampal infarction due to atherosclerotic-thrombotic or embolic occlusion of the posterior cerebral arteries or their inferior temporal branches B Bilateral or left (dominant) infarction of anteromedial thalamic nuclei C Infarction of the basal forebrain due to occlusion of anterior cerebral anterior communicating arteries D Subarachnoid hemorrhage (usually rupture of anterior communicating artery aneurysm) E Trauma to the diencephalic, inferomedial temporal, or orbitofrontal regions F Cardiac arrest, carbon monoxide poisoning, and other hypoxic states (hippocampal damage) G Following prolonged status epilepticus H Following delirium tremens II Amnesia of sudden onset and short duration A Temporal lobe seizures B Postconcussive states C Transient global amnesia D Hysteria III Amnesic syndrome of subacute onset with varying degrees of recovery, usually leaving permanent residua A Wernicke-Korsakoff syndrome B Herpes simplex encephalitis C Tuberculous and other forms of meningitis characterized by a granulomatous exudate at the base of the brain IV Slowly progressive amnesic states A Tumors involving the oor and walls of the third ventricle and limbic cortical structures B Alzheimer disease (early stage) and other degenerative disorders with disproportionate affection of the temporal lobes C Paraneoplastic and other forms of immune limbic encephalitis

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anisms that govern immediate registration, which remains intact in even the most severely damaged patients with the Korsakoff amnesic syndrome Equally obscure are the anatomic arrangements that enable the patient with virtually no capacity to retain any newly presented factual information to still learn some simple perceptualmotor and cognitive skills, even though there may be no memory of having been taught these skills in the rst place Other psychologic features of human memory that must be accounted for by any model purporting to explain this function are the importance of cueing in eliciting learned material and the imprecision of past memories, allowing for unwitting embellishment and false recollection, to the point of fabrication The latter aspect has been a topic of considerable importance in children who have (or have not) been subjected to sexual abuse and in adults and children whose memories of past abuse have been suggested by the examiners (see Schacter) Also of interest are the separate roles of the thalamus, the hippocampi, and the frontal lobes in memory and whether the nature of the amnesia resulting from damage at one site differs from the others That isolated thalamic lesions, without implicating medial temporal areas, can cause a Korsakoff syndrome is evident from the experience with alcoholism 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 seems to us quite dif cult 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 The cellular mechanisms involved in learning and the formation of memories are only beginning to be understood Whether physiologic phenomena such as long-term potentiation or anatomic changes in the dendritic structure of neurons are at the center of memory storage is not known; certainly both are likely to be involved The neurochemical systems that are activated during formation and recall of memory are also obscure Kandel has provided a detailed review of information on this subject (see the References).

imperfectly and with no regard for their normal temporal relationships, giving them a ctional 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 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 led in other regions of the brain; ie, they acquire a separate and autonomous anatomy Several fundamental questions concerning the amnesic syndrome remain unanswered Not known is how a disease process, acting over a brief period of time, not only impairs all future learning but also wipes out portions of a vast reservoir of past memories that had been rmly established for many years before the onset of the illness Also unknown are the anatomic and physiologic mech-

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