Biomedical subjects
M D Kopelman
Publications and source records attributed to M D Kopelman.
The loss of episodic memories in retrograde amnesia: single-case and group studies.
Retrograde amnesia in neurological disorders is a perplexing and fascinating research topic. The severity of retrograde amnesia is not well correlated with that of anterograde amnesia, and there can be disproportionate impairments of either. Within retrograde amnesia, there are various dissociations which have been claimed-for example, between the more autobiographical (episodic) and more semantic components of memory. However, the associations of different types of retrograde amnesia are also important, and clarification of these issues is confounded by the fact that retrograde amnesia seems to be particularly vulnerable to psychogenic factors. Large frontal and temporal lobe lesions have been postulated as critical in producing retrograde amnesia. Theories of retrograde amnesia have encompassed storage versus access disruption, physiological processes of 'consolidation', the progressive transformation of episodic memories into a more 'semantic' form, and multiple-trace theory. Single-case investigations, group studies and various forms of neuroimaging can all contribute to the resolution of these controversies.
Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances.
A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered.
Learning and memory: recent findings.
Recent findings from neuroimaging, event-related potential and lesion investigations reflect a rapidly emerging view that the memory system is widely distributed throughout the cortex. It is clear that the pattern of cortical involvement during encoding and retrieval of memories is critically dependent on the nature and complexity of task demands. This has implications, both for existing models of memory function, and in the methodology of future investigations and the issues they address. No consensus has yet been reached on a number of issues, perhaps most notably the role of the hippocampus in retrieval, but advances in measurement techniques should enable some of these matters to be resolved. Further work must address the complex dynamics of the memory system, the extent to which the same regions underlie different functions, and how different regions interact and reflect common functions.
Structural MRI volumetric analysis in patients with organic amnesia, 1: methods and comparative findings across diagnostic groups.
BACKGROUND: If they are to be replicable, MRI volume measurements require explicit definitions of structures and of criteria for delineating these structures on MRI. Previously published volumes in healthy subjects show considerable differences in measurements across different studies, including a fourfold variation in estimates of hippocampal volume. Previous neuroimaging reports in patients with Korsakoff syndrome have generally found widespread or non-specific change, whereas in patients with herpes encephalitis the extent of pathological involvement reported beyond the temporal lobes has varied. METHOD: In the present study, a clear set of anatomical criteria and detailed MRI segmentation procedures were applied to measure whole brain, frontal and temporal lobe, and anterolateral and medial temporal volumes, as well as thalamic areas in patients with organic amnesia (from Korsakoff's syndrome, herpes encephalitis, and focal frontal lesions) as well as healthy controls. RESULTS: Patients with Korsakoff's syndrome showed decreased thalamic measurements but no significant changes in the medial temporal lobes, whereas patients with herpes encephalitis showed severe medial temporal but not thalamic atrophy. In the patients with known frontal lobe lesions, quantitative analysis on MRI showed reduced frontal lobe volume but no significant temporal lobe or thalamic atrophy. CONCLUSION: Quantified MRI can be a useful technique with which to examine brain-cognitive relations, provided that detailed techniques are explicitly described. In particular, specific patterns of volume change can be found in vivo in patients with Korsakoff's syndrome and those with herpes encephalitis.
Structural MRI volumetric analysis in patients with organic amnesia, 2: correlations with anterograde memory and executive tests in 40 patients.
BACKGROUND: Cognitive-MRI correlations have often been studied in disorders in which there are multiple cognitive deficits and widespread cortical atrophy, such as Alzheimer's dementia. In such circumstances, the interpretation of any single cognitive-structural correlation is equivocal. Only by measuring differing cognitive functions and a wide range of brain structures in patients with a varying distribution of lesions or atrophy can specific brain-cognitive relations be determined in neurological disorder. METHOD: In the present study, a clear set of anatomical criteria and detailed MRI segmentation procedures were applied to measure whole brain, and left and right frontal, temporal lobe, anterolateral and medial temporal volumes, as well as thalamic cross sectional areas in 40 patients with organic amnesia (from various diseases) and 10 healthy controls. RESULTS: Within the total patient group, anterograde memory measures correlated significantly with medial temporal, hippocampal, and thalamic measurements. A spatial memory measure correlated significantly with hippocampal volume, and temporal context memory with frontal volume. After a factor analysis of the cognitive measures, the association between anterograde memory and hippocampal volume was corroborated. Forgetting rates and subjective memory evaluations did not show any significant MR correlations and, of executive tests employed, only card sorting categories correlated significantly with frontal volume. CONCLUSION: Loss of volume in key brain structures (for example, hippocampus, thalamus) is detectable on quantitative MRI, and this loss of volume correlates significantly with impaired performance on measures of anterograde memory function. Correlations with hippocampal volume did not indicate a specific role in either recall or verbal memory, as opposed to recognition or visual memory.
Fear can interrupt the continuum of memory.
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Rapid eye movement sleep behaviour disorder, depression and cognitive impairment. Case study.
BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder is a relatively new diagnostic category. It has never before been associated with a treatable depressive condition. AIMS: To report on a 74-year-old man with a history of depression and REM sleep behaviour disorder, associated with mild cognitive impairment. METHOD: Assessment using brain CT, MRI, PET, electroencephalography, neuropsychological testing and nocturnal polysomnography. RESULTS: Depression was treated with sertraline. Sleep laboratory studies supported a diagnosis of REM sleep behaviour disorder, which was treated with clonazepam. Sleep apnoea, revealed later, was treated with nasal continuous positive airways pressure. Brain MRI showed mild atrophy, but neuropsychological testing indicated no progressive cognitive deterioration. CONCLUSIONS: This case draws attention to REM sleep behaviour disorder and its potential interaction with depression and cognitive impairment, producing symptoms which can be mistaken for early dementia. The diagnosis of REM sleep behaviour disorder is easily missed, and it requires careful history-taking and sleep investigation in all suspected sufferers. Associated neurological, sleep and psychiatric conditions (including depression and cognitive impairment) may confound the diagnosis.
Retrograde amnesia in patients with diencephalic, temporal lobe or frontal lesions.
Patients with focal diencephalic, temporal lobe, or frontal lobe lesions were examined on various measures of remote memory. Korsakoff patients showed a severe impairment with a characteristic 'temporal gradient', whereas two patients with focal diencephalic damage (and anterograde amnesia) were virtually unimpaired on remote memory measures. Patients with frontal lobe pathology were severely impaired in the recall of autobiographical incidents and famous news events. Patients with temporal lobe pathology showed severe impairment but a relatively 'flat' temporal gradient, largely attributable to herpes encephalitis patients. From recognition and cued recall tasks, it is argued that there is an important retrieval component to the remote memory deficit across all the lesion groups. In general, the pattern of performance by the frontal lobe and temporal lobe groups was closely similar, and there was no evidence of any major access/storage difference between them. However, laterality comparisons across these groups indicated that the right temporal and frontal lobe regions may make a greater contribution to the retrieval of past episodic (incident and event) memories, whereas the left temporal region is more closely involved in the lexical-semantic labelling of remote memories.
Unreliable admissions to homicide. A case of misdiagnosis of amnesia and misuse of abreaction technique.
BACKGROUND: The past decade has witnessed a recognition that unsafe criminal convictions may be occasioned by unreliable confessions. AIMS: To present a case which illustrates the dangers of using abreaction interview techniques in a legal context and demonstrate the relevance of the memory distrust syndrome to an unsafe confession to murder. METHOD: We under took a detailed assessment of a person appealing against his original murder conviction, 'the appellant', and a careful scrutiny of all the relevant papers in the case. RESULTS: The appellant served 25 years in prison before his conviction was quashed as 'unsafe' on the basis of fresh psychological and psychiatric evidence. CONCLUSIONS: Amnesia for an offence had been misdiagnosed, and the use of repeated abreaction interviews had further confused both the appellant and the original court. At the Appeal Court, the advice was that the man had experienced a form of source amnesia which resulted in an unreliable confession.
Subjective memory evaluations in patients with focal frontal, diencephalic, and temporal lobe lesion.
This paper examines subjective memory evaluations and their correlates in patients with focal frontal, diencephalic, or temporal lobe lesions. Although all patient groups showed significantly lower subjective memory evaluations than healthy subjects, the temporal lobe group rated themselves significantly lower than the frontal lobe or diencephalic groups despite comparable severity of amnesia, implying more severely impaired 'insight' in the latter two groups. There was a 'temporal gradient' such that patients rated their memory for 'old' (premorbid) items better than their memory for 'new' (recent) or prospective items. As in previous studies, subjective memory evaluations were not correlated with measures of 'objective' anterograde memory performance, but the present study suggests that subjective evaluations are not randomly determined. It seemed to be the site of lesion (frontal and/or diencephalic), rather than underlying aetiology, which produced a particularly severe loss of 'insight'. Whether the earliest remote or autobiographical memories were preserved or not appeared to be an important correlate of current subjective memory evaluations, and patients who had been memory-disordered for longer were more likely to evaluate their memory as poor than those with a more recent onset.
Rates of forgetting in Alzheimer dementia.
Patients diagnosed with Alzheimer's disease (AD) were compared with healthy controls on a picture recognition task, a forced choice word recognition task, a forced choice design recognition task, a picture recall task and a stem completion task. Performance on recognition and word stem completion was assessed at 1, 10 and 20 min after exposure to experimental stimuli, as these are delays across which previous studies had suggested there might be differing forgetting rates. AD patients did not show significantly faster rates of forgetting relative to controls on picture recognition, design recognition, word recognition or stem completion, after levels of learning had been matched as closely as possible. Moreover, once initial learning was equated in a small number of subjects, there were no qualitative differences between AD patients and controls following inclusion and exclusion instructions on the stem completion task. In particular, those AD patients who were matched to controls for initial levels of "recollection" showed comparable forgetting rates in recollection (or cued recall). Although matching was more difficult for a picture recall task, both the main analysis and subgroup analysis indicated faster forgetting in the AD group than controls, suggesting a difference between "free recall" and recognition or cued recall measures, comparable with the finding in a parallel study of organic amnesia.
Recall and recognition memory in patients with focal frontal, temporal lobe and diencephalic lesions.
Patients with frontal, temporal lobe, or diencephalic lesions were compared with healthy controls on measures of recall and recognition memory for word lists. Exposure times were titrated to match recognition memory scores 30 s after the end of word-list presentation as closely as possible. Using this technique, we failed to find a disproportionate impairment in recall memory in either the frontal lobe lesion patients or in the amnesic (temporal lobe and diencephalic) patients, compared with healthy controls. Consistent with this finding, performance on these tasks showed highly significant correlations with anterograde memory quotients (despite the titration procedure), but not with executive/frontal function tasks. On the other hand, the frontal lobe lesion group showed disproportionate benefit in the recall of semantically categorised words, compared with unrelated words. This may indicate an impairment in retrieval or access, compared with the amnesic (temporal lobe and diencephalic) patients, and/or an inability to organise their learning of unrelated words spontaneously, compared with healthy controls.
Frequency judgements of abstract designs by patients with diencephalic, temporal lobe or frontal lobe lesions.
Patients with diencephalic, temporal lobe or frontal lobe lesions were compared with healthy controls on a frequency judgement task. The three patient groups were disproportionately impaired at estimating how often a series of abstract designs had been presented relative to controls. Diencephalic and temporal lobe patients did not differ from each other. It is argued that the results may reflect a 'core' memory deficit in the temporal lobe patients. The impairment in the frontal patients may reflect their difficulty in making an organised search in memory for multiple traces of an item, while the deficit shown by the diencephalic patients (particularly those with Korsakoff syndrome) may be due to the combined effects of a generally poor memory and superimposed frontal pathology.
Does the sedation resulting from sleep deprivation and lorazepam cause similar cognitive deficits?
It is notoriously difficult to assess the contribution of the sedative effects of benzodiazepines to the cognitive impairments that they produce. The purpose of the present experiment was to determine whether a similar pattern of cognitive impairment would be seen in conditions when subjects felt equally sleepy as the result of sleep deprivation. The effects of a sedative dose of lorazepam (2.5 mg) in healthy volunteers was therefore compared with the effects of acute sleep deprivation (a night on-call) in a group of junior doctors and the effects of chronically disturbed sleep due to snoring. Lorazepam, acute sleep deprivation, and chronic sleep disturbance all significantly increased subjective sedation. In addition, lorazepam significantly impaired performance in two tests of psychomotor speed and caused significant anterograde amnesia. Semantic and short-term memory were not impaired by lorazepam, nor was there any impairment in executive function. The only deficit found following acute sleep deprivation was in a test of semantic memory, generating examples from a difficult category. The only significant deficit in the group suffering from chronically disturbed sleep, compared with age-matched controls, was in executive function, and there was a nearly significant impairment in sustained attention. These results suggest that, despite the common factor of increased subjective sedation, the profile of cognitive impairment in the two sleep deprivation groups are neither similar to each other nor to that seen following an acute dose of lorazepam.
PET activation of the medial temporal lobe in learning.
Regional cerebral blood flow was examined during multiple-trial learning in healthy volunteers. On the basis that incremental learning from trial to trial is severely impaired in neuropsychological studies of patients with medial temporal lesions, we predicted that medial temporal activation might be particularly associated with incremental gains in learning. On the other hand, we predicted that frontal activations would not show any increase during incremental learning, and might even diminish. PET recordings were undertaken while subjects were presented visually with a 15-word list in one of three conditions: a list in which a single word was repeated 15 times (S), a list of novel words (N), and a list which was repeated from before (R). We demonstrated that statistically significant incremental learning did occur when word lists were repeated in (R) trials. The subtraction of novel minus repeated conditions (N-R) was associated with left medial temporal as well as left prefrontal activations, whereas the opposite (R-N) subtraction gave rise to right prefrontal and precuneal activations. In particular, incremental learning during the repeated trials (R) identified a left medial temporal activation, as predicted, but the left frontal activation was no longer evident. We suggest that the left medial temporal region is not only activated by novel, to-be-learned stimuli, but it also contributes to incremental learning as part of a network involved in 'binding' or 'consolidating' new memories. The right frontal and precuneal regions, which participate in the repeated retrieval and rehearsal of already learned memories, are also involved in this network. The left frontal region is implicated in the more 'effortful' or elaborative aspects of memory.
Cognitive effects of pituitary tumours and their treatments: two case studies and an investigation of 90 patients.
OBJECTIVES: Two case studies are reported of patients with pituitary adenomas who had been treated with trans-sphenoidal surgery, one with and one without adjunctive radiotherapy, in whom memory impairment was found. Further to this, neuropsychological investigations of 90 patients were carried out (1) to establish the prevalence of such deficits, and (2) to try to determine their cause. METHODS: Two case studies are described. For the expanded study, patients were recruited from the data base of the endocrinology department of St Thomas's Hospital, London, if they had previously been treated for a pituitary adenoma in the past 30 years. Ninety patients were contacted and assessed with a wide range of neuropsychological tests. They were divided into five treatment groups: those who had received transfrontal surgery with radiotherapy, trans-sphenoidal surgery with or without radiotherapy, radiotherapy only, and a bromocriptine therapy group, as well as a group of 19 healthy control subjects matched for age and sex. RESULTS: In the two patients presented, both showed severe memory impairments compared with their intact intellectual ability. The more severely affected patient had received adjunctive radiotherapy, and superimposition of the 90% isodose fields on a postoperative MRI examination suggested involvement of the diencephalic structures. In the group study, significant deficits in anterograde memory were also obtained on two measures (WMS-R, RMT) for all patient groups when compared with the healthy controls, although these impairments varied in degree and were less in the bromocriptine group. However, the individual surgical and radiotherapy treatment groups did not differ significantly from one another. By contrast, general intellectual function (IQ) remained intact for all groups, as did performance on supplementary cognitive tests, including measures of frontal lobe or "executive" function, language comprehension, and speed of mental processing. Psychiatric morbidity and tumour aetiology did not seem to relate to the presence of memory deficits. CONCLUSIONS: Anterograde memory deficits were seen in the two case studies and in all our treatment groups when compared with the healthy controls, and these occurred in the context of preserved intellectual function. The present findings suggest that these memory deficits result from treatment rather than from the underlying tumour, but there was no difference between the effects of surgery and radiotherapy. It is suggested that they result from damage to diencephalic structures implicated in memory.
Forgetting rates in neuropsychiatric disorders.
OBJECTIVE: Previous studies have attributed accelerated forgetting rates on recognition memory tasks to temporal lobe pathology, but findings in some patient groups may have been attributable to metabolic disruption. Findings in psychiatric disorders such as schizophrenia are conflicting. The purpose of the present study was to compare forgetting rates in patients with confusional states (post-electroconvulsive therapy (post-ECT), delirium), with those obtained in schizophrenic patients (with putative temporal lobe pathology), non-ECT depressed patients, and healthy controls. The findings could also be compared with previous reports in patients with head injury, focal structural lesions, and Alzheimer's dementia. METHODS: Two studies employed a picture recognition task to examine forgetting rates, the first between delays of 1 minute, 15 minutes, and 30 minutes, and the second between delays of 10 minutes, 2 hours, and 24 hours. RESULTS: There were no significant differences in forgetting rates between 1 minute and 30 minutes, but the ECT group showed accelerated forgetting between 10 minutes and 2 hours compared with healthy controls, associated with a rapid decline in "hit rate". This was not attributable to differential changes in either depression or severity of memory impairment. There were no differences in forgetting rates across the other subject groups. CONCLUSION: Post-ECT confusional state patients (similarly to "within post-traumatic amnesia" patients with head injury) show accelerated forgetting on a recognition memory task and, in this, they contrast with patients who have focal structural lesions or widespread cortical atrophy. Accelerated forgetting may reflect the effect of disrupted cerebral metabolism on either "consolidation" or memory "binding" processes.