Biomedical subjects

M D Kopelman

Publications and source records attributed to M D Kopelman.

At least 37 records · Page 2Linked to original sources

PubMed1998

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed1998

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.

Adenoma↗

PubMed1998

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.

Adult↗

PubMed1997

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions.

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.

Adult↗

PubMed1997

Rates of forgetting in organic amnesia following temporal lobe, diencephalic, or frontal lobe lesions.

Forgetting rates were examined in patients with diencephalic, temporal lobe, or frontal lesions. No significant differences were found in short-term forgetting of verbal and nonverbal material; in recognition memory for pictures, words, or designs over delays between 1 min and 20 or 30 min; or on a measure of explicit cued recall for words, calculated in terms of the process dissociation procedure. Significantly faster forgetting was found in the diencephalic and the temporal lobe groups in the free recall of pictures of objects, although there was no difference between these 2 groups. It is concluded that the major deficit in amnesic patients' memory processes is in the initial acquisition of information but that there is a subtler deficit in retention over specific delays, detectable only on measures of free recall.

Adolescent↗

PubMed1996

What's wrong and what's right in neuropsychology and neuropsychiatry.

There has been a recent converging of interests by psychiatrists and psychologists in subjective mental phenomena. Examples of topics where these converging interests arise include the relationship of confabulation and delusional memories, the nature of face-processing deficits in prosopagnosia and the Capgras delusion, and hierarchial models of psychological function. These developments are very much welcomed; but the over-interpretation of neuropsychological test findings in neuropsychiatry, and the occasional failure to take account of clinical context (particularly the psychiatric background) in neuropsychology, are also noted. Cognitive neuropsychiatry appears to have emerged as a label to identify this converging of interests, modelling itself on cognitive neuropsychology. The potential benefits and limitations of such an approach are discussed.

Journal Article↗

PubMed1995

The Korsakoff syndrome.

BACKGROUND: Investigations of the Korsakoff syndrome by researchers from different disciplines have proliferated in recent years, making it apposite to review the various findings. METHOD: This review is based on the author's knowledge of reports in the major clinical and neuropsychological journals, supplemented by Medline searches to update particular subtopics. RESULTS: The Korsakoff syndrome is defined as a disproportionate impairment in memory, relative to other aspects of cognitive function, resulting from a nutritional (thiamine) depletion. The initial manifestations of the disorder are variable, and a persistent memory impairment can result from a non-alcoholic aetiology, although this seems to happen much less commonly than in the past - presumably because of generally higher standards of nutrition. Although there is agreement on the underlying neuropathology, the critical lesion sites for memory disorder have been debated. Recent evidence suggests that the circuit involving the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus, rather than the medial dorsal nucleus of the thalamus, is particularly critical in the formation of new memories. The relationship of these deficits to thiamine depletion remains a topic of current investigation, as does the purported role of neurotransmitter depletions in the cholinergic, glutamate/GABA and catecholamine and serotonergic systems. Neuro-imaging studies have confirmed autopsy findings of more widespread structural and metabolic abnormalities, particularly involving the frontal lobes. CONCLUSIONS: The relationship of these neuropathological, neurochemical, and metabolic abnormalities to cognitive functioning, with particular reference to specific aspects of memory processing, has been considered in some detail. Whereas structural and/or neurochemical abnormalities within the limbic/diencephalic circuits account for anterograde amnesia, some other factor, such as frontal lobe dysfunction, must underlie the severe retrograde memory loss which is characteristically found in this syndrome.

Acetylcholine↗

PubMed1994

The great escape: a neuropsychological study of psychogenic amnesia.

This paper describes the neuropsychological test performance of a patient who experienced a "fugue" episode (functional retrograde amnesia) lasting 7 days, but who continued to complain of a virtually complete loss of autobiographical memory for well over a year. Subsequent evidence revealed that she had been at least partially simulating her amnesia during this prolonged period. Neuropsychological testing took place soon after admission to hospital, at intervals thereafter, and after an Amytal abreaction, which produced a substantial recovery of her memories. On various anterograde tests, designed to detect simulation, the patient's performance was unimpaired, including recognition memory tasks, word-stem completion priming for "neutral" word-lists and for post-onset autobiographical material, and some aspects of semantic memory. However, her pattern of performance on an autobiographical and a remote News Event test differentiated her from patients with organic amnesia, because she showed a grossly disproportionate autobiographical memory loss and an extreme recency effect. In addition, a rating scale, on which she showed impaired feelings-of-knowing for items from her autobiographical memory, suggested simulation. On a word-completion task for pre-onset autobiographical material, she showed absent "priming" relative to "baseline" material. However, following the Amytal abreaction, there was a substantial improvement on this task, relative to recognition and cued recall performance. This finding has been interpreted within an hierarchical model of awareness in memory, derived from studies of normal memory and organic amnesia; and it is suggested that patients with "psychogenic amnesia" may manifest different levels of awareness for differing memories.

Adult↗

PubMed1994

The case of the amnesic intelligence officer.

This paper describes a patient whose amnesia for an offence (fraud) and two fugue episodes occurred against the background of an underlying organic amnesia. The fugue states conformed in their duration and precipitating factors to previous accounts in the literature. The organic, anterograde memory impairment was attributed to multiple small infarcts and a larger infarction in the left medial temporal lobe, which were evident on MRI and PET scans after the patient had developed transient neurological signs. At follow-up, the anterograde amnesia had persisted, and the patient also showed some difficulty in retrieving autobiographical memories of past incidents or events, although other aspects of his retrograde memory were intact (including his knowledge of facts about his past life and his general knowledge of public events). The difficulty in retrieving autobiological incidents may have resulted from the presence of a moderate degree of frontal lobe dysfunction or, just possibly, from ischaemia in the left anterior temporal lobe. The persistence of the organic memory impairment and the importance of both the clinical history and neuropsychological testing in assessment are discussed, as well as the need to examine for possible organic factors in patients who may initially appear to manifest purely 'psychogenic' memory loss.

Accounting↗

PubMed1994

The Autobiographical Memory Interview (AMI) in organic and psychogenic amnesia.

The Autobiographical Memory Interview (AMI) is a semi-structured interview, sampling a subject's recollections across three broad time-periods. In patients with organic amnesia or dementia, there is an impairment in recalling both autobiographical facts and incidents, and there is a temporal gradient such that early memories are relatively spared. Correlations with measures of anterograde memory are relatively low, and lesions affecting the frontal lobes, anterior temporal poles, the posterior-medial temporal lobes, or even projections from the occipital lobes, can impair retrieval of autobiographical memories. In schizophrenia, an impairment in retrieving autobiographical incidents, comparable with organic amnesia, has been reported in some patients. However a patient with delusional memories secondary to schizophrenia is cited, in whom AMI performance was normal. Finally, patients with psychogenic amnesia show a variable pattern of performance, but, in general, there is a disproportionate impairment of autobiographical memory, and often an anomalous temporal gradient, which can recover subsequently.

Alcohol Amnestic Disorder↗

PubMed1994

Transient epileptic amnesia differentiated from psychogenic "fugue": neuropsychological, EEG, and PET findings.

A patient had repeated episodes of transient loss of memory, which had been attributed to psychogenic causes. Preservation of his sense of personal identity and the presence of repetitive questioning indicated an organic basis, however, and the multiplicity of the attacks and their brief duration suggested an epileptic aetiology. Although three standard EEGs, CT and MRI were all normal, two sleep EEGs confirmed bilateral foci in the temporal lobes. The attacks responded to an anticonvulsant. A fluoro-deoxyglucose PET scan, performed a few months after the most recent attack, was normal. The patient also had impaired anterograde memory that persisted six months after recovery from the acute attacks.

Amnesia↗

PubMed1991

Non-verbal, short-term forgetting in the alcoholic Korsakoff syndrome and Alzheimer-type dementia.

On a non-verbal, short-term forgetting task, Alzheimer patients showed a severe impairment and Korsakoff patients a more moderate impairment. At block span, less demanding of information-processing resources. Alzheimer patients were impaired and Korsakoff patients intact. The pattern of results suggested that the impairment resulted from diminished processing resources and/or an encoding or retrieval deficit, rather than from accelerated decay of the memory trace, although this latter possibility could not be completely excluded. The impairment involved memory for location or position, and there was no evidence that "short-term" memory for sequence was disproportionately affected. The deficit correlated with the degree of general, cortical atrophy evident on a CT scan and with a measure of right hemisphere dysfunction (picture arrangement errors). Together, these findings suggest that right hemisphere atrophy may underlie the deficit in non-verbal, "short-term" tests. The results are compared with those obtained in previous studies employing a verbal, short-term forgetting (Brown-Peterson) task.

Aged↗

PubMed1991

Frontal dysfunction and memory deficits in the alcoholic Korsakoff syndrome and Alzheimer-type dementia.

This study investigated the intercorrelation of 8 'frontal' tests in 32 patients with Korsakoff's syndrome and Alzheimer's disease, and examined the relationship of frontal dysfunction to impaired release from proactive interference and impoverished retrieval from retrograde memory. Amongst the frontal tests, there were statistically significant intercorrelations between 3 'fluency' tests and 3 'card-sorting' tests, although the degree of shared variance was relatively low. The relationship of another test--picture arrangement errors--was more equivocal; performance for 'cognitive estimates' was unrelated to performance in the other frontal tests, possibly because it may reflect pathology at a different frontal site. There was no evidence in this study that variability in release from proactive interference was related to measures of frontal function in either patient group, and the conditions under which these patient groups fail to show 'normal' release appear to be tightly constrained. On the other hand, the defective retrieval of retrograde memories was correlated with frontal dysfunction in both patient groups. There was a suggestion of a double dissociation with a measure of nonverbal short-term forgetting, impairment at which was related to the degree of general cortical atrophy rather than frontal dysfunction. A stepwise regression equation based on 3 frontal tests could account for 64% of the variability in retrograde memory performance within the total patient group, 68.5% in the Korsakoff group and 57% in the Alzheimer group. By comparison, the severity of anterograde memory impairment predicted only 21% of the variance in retrograde memory performance. It is concluded that frontal dysfunction produces a disorganization of retrieval processes which contributes to the temporally-extensive retrograde amnesia of these two disorders.

Aged↗

PubMed1989

Rates of forgetting in normal ageing: a comparison with dementia.

This paper examines the effect of normal ageing on the forgetting rate of visuo-spatial material in a sample of 74 subjects, aged between 16 and 83. It finds that normal ageing produces a mild acquisition deficit as well as a significant increase in the forgetting rate; and it demonstrates that the relatively rapid rate of forgetting in the elderly cannot be accounted for by differences in the initial level of acquisition. The present result is contrasted with that obtained in studies of dementia and the Korsakoff syndrome, which have demonstrated a profound acquisition deficit but a normal forgetting rate once initial learning has been accomplished. Possible explanations of these differing patterns of results are briefly considered.

Adolescent↗

PubMed1989

Remote and autobiographical memory, temporal context memory and frontal atrophy in Korsakoff and Alzheimer patients.

Korsakoff and Alzheimer patients were assessed on tests of remote, autobiographical, and temporal context memory. On the remote memory tests, both groups showed a temporal gradient across all the measures used, although the gradient was significantly steeper in the Korsakoff group. Both groups also showed a marked improvement in performance on recognition testing. Correlations with an anterograde "memory quotient" were relatively low, and in the Korsakoff group, there was evidence of partial independence between memory for personal events/facts and memory for public events/facts. Better performance within the Korsakoff group in the recall of early memories was correlated with higher intelligence, whereas worse performance for recent memories was associated with a longer duration of the disorder. Both patient groups were impaired at tests of retrospective and anterograde temporal context memory, but there was no association with a neuroradiological measure of frontal atrophy and only a very weak correlation with tests of frontal function. It is concluded that both patient groups show a retrieval deficit in remote memory, that a superimposed anterograde impairment produces the steeper temporal gradient in Korsakoff patients, and that the deficit in temporal context memory is unlikely to be related to frontal atrophy or frontal dysfunction.

Adult↗

PubMed1989

The autobiographical memory interview: a new assessment of autobiographical and personal semantic memory in amnesic patients.

This paper describes a new technique for assessing "autobiographical" and "personal semantic" memory in amnesic patients and healthy controls. It provides evidence of the reliability and validity of the procedure, and reports an age-related temporal gradient in amnesic patients. The results are considered in terms of the severity, the rate of onset, and the duration of the amnesia; and a preliminary analysis is given of the findings in different diagnostic groups. The findings indicate that autobiographical and personal semantic memory show a consistent pattern of impairment, when a comparison is made which controls for the age of the memories and the subject's own past experience.

Adult↗

PubMed1988

Cholinergic 'blockade' as a model for cholinergic depletion. A comparison of the memory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome.

The effect of cholinergic 'blockade' on human memory performance as a model for the effect of cholinergic depletion in clinical disorders was investigated. A wide range of memory functions was assessed in 70 subjects, using tests which were identical or closely similar to those which have previously been employed in clinical studies of Alzheimer and Korsakoff patients. In addition, a physiological measure of the degree of central cholinergic blockade was included, as well as measures of subjective arousal and objective attention. It was found that cholinergic blockade had no significant effect on the more passive aspects of primary (or 'working') memory, namely span tests and a measure of verbal short-term forgetting; in this, it contrasts with the marked deficits seen in Alzheimer-type dementia. On the other hand, cholinergic blockade produced impairment at a visuospatial short-term forgetting test, and at a verbal test in which the distractor task was made more difficult. On tests of secondary memory, cholinergic blockade produced a pattern similar to that seen in the anterograde amnesia of Alzheimer and Korsakoff patients, namely a pronounced impairment in learning verbal and visuospatial material, a 'normal' forgetting rate once learning had been accomplished, and relative preservation of the response to priming and of skill learning (procedural memory). Cholinergic blockade, however, did not produce a retrograde amnesia, nor did it affect the recall of temporal context or of long-established semantic knowledge. This pattern of results is compared with that obtained in previous studies of Alzheimer and Korsakoff patients.

Alcohol Amnestic Disorder↗