Amnesia, Organic

views updated

AMNESIA, ORGANIC

Organic amnesia is a neurological disorder characterized by a dense impairment of memory in the context of normal intelligence and other preserved mental abilities. Investigations of patients with this disorder have enhanced the understanding of the psychological processes involved in learning and remembering, as well as the brain organization of human memory.

Much of the current interest in memory and brain function finds its origin in the study of patient H.M., a man who, in 1953, underwent surgery for treatment of refractory seizures (Scoville and Milner, 1957). The surgery involved bilateral resection of a large portion of the medial temporal region, which includes the amygdala, hippocampus, and hippocampal gyrus. Although the surgery was successful in substantially reducing H.M.'s seizures, the procedure produced a pervasive impairment of memory (Milner, Corkin, and Teuber, 1968). Since the time of his surgery at the age of twenty-seven, H.M. has been unable to consciously learn and remember new information (anterograde amnesia). For example, thirty minutes after eating lunch, H.M. cannot recall what he ate for lunch, nor can he recall if in fact he ate lunch at all. He exhibits severe impairment on laboratory tests of word and picture recall, cued-word learning (e.g., learning word pairs), and recognition memory. His impairment is global in nature: information received from all sensory modalities is affected, and both verbal and nonverbal (e.g., spatial) memory are impaired. H.M. also evidences deficient recall of remote memories antedating the surgery (retrograde amnesia). For instance, H.M. could not recall the death of a favorite uncle who had died three years prior to the surgery. Moreover, nearly all of his personal memories are from the age of sixteen or earlier (Sagar, Cohen, Corkin, and Growdon, 1985).

Despite the severity of his amnesia, H.M. exhibits normal attention, language, and general intellectual abilities. His performance on tasks of immediate, or working, memory is relatively preserved. That is, he can temporarily store and maintain information over a brief interval, such as that required when rehearsing a telephone number. But if he is distracted or prevented from continually rehearsing the material, the information is forgotten. H.M. exhibits preservation of some long-term memory functions, such as skill and habit learning, where learning is expressed as enhanced task performance. The detailed examination of H.M.'s amnesia has served as a milestone in the quest to elucidate the functional and neuroanatomical basis of memory and has spawned decades of research into the memory processes that are impaired and preserved in amnesia.

Etiologies of Amnesia

Although H.M. still serves as a benchmark for characterizing global amnesia, it has also become clear that the disorder is composed of a number of different patterns of memory loss that may be linked to distinct etiologies and associated patterns of brain damage. Organic amnesia has been associated with a wide range of medical conditions including vascular accidents (i.e., strokes), ischemia (e.g., loss of blood flow to the brain), anoxia (i.e., loss of oxygen to the brain), viral infections, and Wernicke-Korsakoff syndrome. As with H.M., patients with these medical conditions typically show preserved attention, working memory, and general intellectual abilities.

Not all forms of amnesia are permanent. For example, head injury can cause transient and selective memory impairment. Anterograde amnesia following head trauma can last minutes, days, or even weeks. Depending on whether the trauma is mild or severe, patients may completely regain their learning ability or may suffer long-lasting and sometimes permanent impairment. Retrograde amnesia may also occur, and the temporal extent of retrograde amnesia is often correlated with the severity of anterograde amnesia. Quite severe memory problems also occur after electroconvulsive therapy (ECT), a procedure sometimes prescribed for treatment of severe depression. However, ECT-induced amnesia is usually transient, and extensive recovery of memory occurs with time.

The Anatomy of Memory

Analysis of the locus of brain lesions in patients such as H.M. has underscored the importance of the medial temporal region, particularly the hippocampus and adjacent regions, in new learning. Further insight into the prominent role of the hippocampus in memory comes from the study of patient R.B. by Zola-Morgan, Squire, and Amaral (1986). R.B. became amnesic in 1978 when he suffered an ischemic episode during open-heart surgery. Neuropsychological assessment of R.B. revealed moderate level antero-grade amnesia alongside mild retrograde amnesia. In 1983, R.B. suffered a fatal cardiac arrest and his brain was brought to autopsy. Examination of his brain revealed that R.B. had sustained discrete bilateral brain damage restricted to a portion of the hippocampus called the CA1 subfield. Several other cases of amnesia resulting from ischemia have come to autopsy since then (Rempel-Clower, Zola, Squire, and Amaral, 1996). These cases have revealed that more extensive damage to the hippocampal formation produces more severe anterograde amnesia, as well as extensive retrograde amnesia for memories predating the brain injury up to fifteen years or more. In many patients, lesions extend beyond the hippocampal formation to include adjacent regions (i.e., entorhinal and perirhinal). This typically leads to dense anterograde and retrograde amnesia. Importantly, comparisons between patients with restricted versus extensive medial temporal lesions suggest that the hippocampal formation and adjacent regions make qualitatively different contributions to memory. It has been suggested that one neural circuit centered in the hippocampus supports recollection (i.e., the conscious or intentional retrieval of past experiences) whereas another neural circuit centered in adjacent perirhinal regions mediates overall feelings of familiarity (i.e., the subjective sense that something was encountered previously) (Aggleton and Brown, 1999; Brown and Aggleton, 2001).

Damage to another region of the brain, the diencephalic midline, can also produce organic amnesia. This brain region includes various midline thalamic nuclei (nuclei are groups of neurons), as well as subthalamic nuclei. These neurons serve as relay groups, sending and receiving projections to numerous parts of the brain, including the medial temporal region. The best-studied cases of amnesia resulting from damage to diencephalic midline structures are patients with Wernicke-Korsakoff syndrome, an amnesic disorder resulting from the convergent effects of chronic alcohol abuse and malnutrition. Studies of postmortem brain tissue by Victor, Adams, and Collins (1989) have revealed bilateral damage involving the dorsomedial nucleus of the thalamus and a subthalamic nucleus called the mamillary bodies. Similar pathology can also occur in nonamnesic alcoholics, but what distinguishes patients with Wernicke-Korsakoff syndrome is that they also show neuronal loss in anterior thalamic nuclei (Harding, Halliday, Caine, and Kril, 2000). Cortical atrophy (i.e., brain-cell loss) and cerebellar damage are also often observed. On neuropsychological tests Wernicke-Korsakoff patients evidence both anterograde amnesia and retrograde amnesia. In addition, these patients may exhibit attention and problem-solving impairments, as well as impaired insight. These additional difficulties may occur as a result of cortical atrophy, especially in prefrontal areas.

Declarative Memory in Amnesia

Globally amnesic patients are severely impaired at consciously and intentionally remembering information. This deficit encompasses the acquisition, long-term retention, and retrieval of both personally experienced events (i.e., episodic memory) and impersonal information (i.e., semantic memory). Collectively, these forms of memory are referred to as declarative memory.

Episodic memory enables individuals to remember experiences from their personal past (e.g., remembering what they ate for breakfast this morning). Episodic memories contain a multitude of sources of information including perceptual, conceptual, and emotional components. Episodic memories are not stored in isolation, but are placed within a context of personally relevant information. A pervasive deficit in episodic memory is dramatically exemplified by globally amnesic patients. In the clinic, episodic memory is assessed by tests of recall and recognition. Because these tasks require intentional retrieval of recent experiences, they are referred to as tests of explicit memory. Although both recall and recognition require intentional retrieval, their processing demands are not identical. Recognition memory is based on two distinct memory processes: recollection, an effort-dependent process by which information is deliberately brought to mind (e.g., remembering what book you read last night); and familiarity, a facilitation of or fluency in stimulus processing that results from prior experience with that stimulus (e.g., the sense of familiarity when seeing a person on the bus, even though you may not remember when you last saw him or her). By contrast, recall depends largely on recollection. Most globally amnesic patients evidence deficits both on recall and on recognition tests, but their recall performance is typically worse than their recognition performance (Giovanello and Verfaellie, 2001). This finding suggests that recollection may be more severely disrupted in amnesia than is familiarity (Yonelinas et al., 1998).

Whereas episodic memory is concerned with personally experienced events, semantic memory refers to the acquisition and long-term retention of generic factual information. Semantic knowledge encompasses a wide range of information, including facts about the world (e.g., the knowledge that Rome is the capital of Italy), the meanings of words and concepts (e.g., an understanding of the concept Website), and the names attached to objects and people (e.g., the knowledge that William Shakespeare wrote Hamlet). Studies of H.M. (Gabrieli, Cohen, and Corkin, 1988) and other amnesic patients (Verfaellie, Reiss, and Roth, 1995) suggest that semantic learning is impaired in amnesia. For example, H.M. has been unable to acquire any new vocabulary words that entered the language since his surgery. Other amnesic patients, however, appear able to acquire some new semantic information, and occasionally semantic learning is quite good despite a patient's severe impairment in episodic memory (Verfaellie, 2000). For example, Jon, a young patient who became amnesic following an anoxic episode at birth, has been able to acquire a considerable amount of semantic knowledge, as demonstrated by his ability to attend mainstream schools, despite his pronounced amnesia for day-to-day events, such as remembering conversations or television programs (Baddeley, Vargha-Khadem, and Mishkin, 2001). The degree to which semantic learning is still possible in amnesic patients likely depends on the extent of lesion in the temporal lobe.

Nondeclarative Memory in Amnesia

One of the most striking findings about amnesia is that, despite their severe impairment in conscious, intentional retrieval of information (declarative memory), amnesic patients can acquire several forms of memory normally. These forms of memory are collectively referred to as nondeclarative memory. One form of nondeclarative memory is procedural learning, the ability to acquire new perceptual and motor skills on the basis of repeated practice (e.g., learning to ride a bicycle). Studies of H.M. were among the first to establish the preservation of procedural learning in patients with global amnesia. For instance, during one task, H.M. had to learn how to keep a metal stylus in contact with a revolving disc. He learned to adapt his motor movement to the movement of the disc and gradually got better at the task, just like nonamnesic individuals. Strikingly, however, H.M. had no awareness of having practiced the task.

Another form of nondeclarative memory is repetition priming, the facilitation in performance induced by previous exposure to stimuli. A typical priming experiment is composed of a "study" phase followed by a "test" phase. During the study phase, participants are exposed to a list of words or pictures. For example, participants might see a list containing the word apricot. During the subsequent test phase, participants are asked to perform a seemingly unrelated task. For example, they may be asked to identify briefly flashed words or to generate as many words as possible when cued with the semantic category "fruit." Priming is measured as the change in accuracy or the bias in task performance induced by recent exposure to task stimuli (e.g., enhanced accuracy at identifying the word apricot or enhanced likelihood of generating the word apricot), compared to a test condition in which apricot did not appear on the prior study list.

Priming in amnesia has been assessed using tasks that require analysis of the perceptual attributes of a stimulus (perceptual priming), such as identification of briefly presented words or pictures and speeded reading of words. Priming has also been assessed using tasks that require analysis of the meaning of a stimulus (conceptual priming), such as category exemplar generation and production of word associates. Amnesic patients show intact priming on both perceptual and conceptual priming tasks, suggesting that these forms of unaware memory do not depend on the medial temporal regions implicated in amnesia. The neural basis of conceptual priming is not well understood, but findings of impaired visual perceptual priming in patients with occipital lesions suggest that perceptual priming is mediated by posterior cortical areas that process modality-specific information (Verfaellie and Keane, 1997).

Remote Memory in Amnesia

Globally amnesic patients evidence deficits in memory for events and for facts predating the onset of their amnesia, although the extent of retrograde memory loss varies from patient to patient. Retrograde amnesia tends to follow Ribot's law, which states that memory for the recent past is more severely affected than memory for the remote past. This pattern of retrograde memory loss provides clues about the mechanisms and time course involved in the storage and retrieval of new memories. Although the medial temporal region plays a critical role in the permanent laying down of information, these brain areas are not the ultimate repositories for new memories. Storage of new memories requires interaction between medial temporal and neocortical (outer brain) regions. The hippocampal formation receives information from a number of neocortical sites and binds together the spatial, perceptual, conceptual, and emotional components of an experience. Subsequent attempts to retrieve this experience cause the hippocampus to reactivate the neocortical sites that contain the information. Reactivation of the neocortical sites leads to a strengthening of the connections between these sites and, over time, allows memories to be retrieved without assistance from the hippocampal formation (Alvarez and Squire, 1994). Consequently, in patients with damage to medial temporal or connected diencephalic structures, information that has not been fully consolidated is vulnerable, whereas fully consolidated older memories can still be retrieved.

Conclusion

Neuropsychological investigations of patients with organic amnesia have contributed greatly to the understanding of memory processes and the brain regions that mediate them. Damage to medial temporal regions or diencephalic midline structures produces a pervasive amnesic disorder in which conscious or declarative memory is severely impaired. In contrast, various forms of nondeclarative memory such as procedural memory and repetition priming are preserved, suggesting that nondeclarative memory is not mediated by the medial temporal region implicated in amnesia. These theoretical advances provide the opportunity for more sophisticated assessment of patients with memory impairments and may lead to the development of new rehabilitation techniques that capitalize on preserved forms of memory.

Bibliography

Aggleton, J. P., and Brown, M. W. (1999). Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behavioral and Brain Sciences 22, 425-489.

Alvarez, P., and Squire, L. R. (1994). Memory consolidation and the medial temporal lobe: A simple network model. Proceedings of the National Academy of Sciences of the United States of America 91, 7,041-7,045.

Baddeley, A., Vargha-Khadem, F., and Mishkin, M. (2001). Preserved recognition in a case of developmental amnesia: Implications for the acquisition of semantic memory? Journal of Cognitive Neuroscience 13, 357-369.

Brown, M. W., and Aggleton, J. P. (2001). Recognition memory: What are the roles of the perirhinal cortex and hippocampus? Nature Review Neuroscience 2, 51-61.

Gabrieli, J. D. E., Cohen, N. J., and Corkin, S. (1988). The impaired learning of semantic knowledge following bilateral medial temporal-lobe resection. Brain and Cognition 7, 525-539.

Giovanello, K. S., and Verfaellie, M. (2001). The relationship between recall and recognition in amnesia: Effects of matching recognition between patients with amnesia and controls. Neuropsychology 15, 444-451.

Harding, A., Halliday, G., Caine, D., and Kril, J. (2000). Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain 123 (1), 141-154.

Milner, B., Corkin, S., and Teuber, H.-L. (1968). Further analysis of the hippocampal amnesia syndrome: Fourteen-year followup study of H.M. Neuropsychologia 6, 215-234.

Rempel-Clower, N. L., Zola, S. M., Squire, L. R., and Amaral, D. G. (1996). Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation. Journal of Neuroscience 16, 5,233-5,255.

Sagar, H. J., Cohen, N. J., Corkin, S., and Growdon, J. H. (1985). Dissociations among processes in remote memory. In D. S. Olton, E. Gamzu, and S. Corkin, eds., Memory dysfunctions: An integration of animal and human research from preclinical and clinical perspectives, Vol. 4, pp. 533-535. New York: New York Academy of Sciences.

Scoville, W. B., and Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery, and Psychiatry 20, 11-21.

Verfaellie, M. (2000). Semantic learning in amnesia. In Handbook of neuropsychology, 2nd edition, Vol. 2: Memory and its disorders, ed. L. S. Cermak, pp. 335-354. Amsterdam: Elsevier Science. Verfaellie, M., and Keane, M. M. (1997). The neural basis of aware and unaware forms of memory. Seminars in Neurology 17, 75-83.

Verfaellie, M., Reiss, L., and Roth, H. (1995). Knowledge of new English vocabulary in amnesia: An examination of premorbidly acquired semantic memory. Journal of the International Neuropsychological Society 1, 443-453.

Victor, M., Adams, R., and Collins, G. (1989). The Wernicke- Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition. Philadelphia: F. A. Davis.

Yonelinas, A. P., Kroll, N. E., Dobbins, I., Lazzara, M., and Knight, R. T. (1998). Recollection and familiarity deficits in amnesia: Convergence of remember-know, process dissociation, and receiver operating characteristic data. Neuropsychology 12, 323-339.

Zola-Morgan, S., Squire, L. R., and Amaral, D. G. (1986). Human amnesia and the medial temporal region: Enduring memory impairment following bilateral lesion limited to the field CA1 of the hippocampus. Journal of Neuroscience 6, 2,950-2,967.

Arthur P.Shimamura

Revised byKelly SullivanGiovanello

andMiekeVerfaellie

Learning and Memory