Retrograde amnesia and the volume of critical brain structures.

There are many controversies concerning the structural basis of retrograde amnesia (RA). One view is that memories are held briefly within a medial temporal store ("hippocampal complex") before being "consolidated" or reorganised within temporal neocortex and/or networks more widely distributed within the cerebral cortex. An alternative view is that the medial temporal lobes are always involved in the storage and retrieval (reactivation) of autobiographical memories (multiple trace theory). The present study used quantitative magnetic resonance imaging (MRI) in 40 patients with focal pathology/volume loss in different sites, to examine the correlates of impairment on three different measures of RA. The findings supported the view that widespread neural networks are involved in the storage and retrieval of autobiographical and other remote memories. Brain volume measures in critical structures could account for 60% of variance on autobiographical memory measures (for incidents and facts) in diencephalic patients and for 60-68% of variance in patients with frontal lesions. Significant correlations with medial temporal lobe volume were found only in the diencephalic group, in whom they were thought to reflect thalamic changes, but not in patients with herpes encephalitis or hypoxia in whom the temporal lobes were particularly implicated. The latter finding fails to support one of the main predictions of multiple trace theory, as presently expounded.

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.

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.

An evaluation of adverse incident reporting.

To examine the reliability of adverse incident-reporting systems we carried out a retrospective review of the mother and baby case notes from a series of 250 deliveries in each of two London obstetric units. Notes were screened for the presence of adverse incidents defined by lists of incidents to be reported in accordance with unit protocols. We assessed the percentage of adverse incidents reported by staff to the maternity risk manager at each unit; the percentage of incidents detected by each risk manager, but not reported; and the percentage of incidents identified only by retrospective case note review. A total of 196 adverse incidents was identified from the 500 deliveries. Staff reported 23% of these and the risk managers identified a further 22%. The remaining 55% of incidents were identified only by retrospective case-note review and not known to the risk manager. Staff reported about half the serious incidents (48%), but comparatively few of the moderately serious (24%) or minor ones (15%). The risk managers identified an additional 16% of serious incidents that staff did not report. Drug errors were analysed separately; only two were known to the risk managers and a further 44 were found by case-note review. Incident-reporting systems may produce much potentially valuable information, but seriously underestimate the true level of reportable incidents. Where one risk manager covers an entire trust, rather than a single unit, reporting rates are likely to be very much lower than in the present study. Greater clarity is needed regarding the definition of reportable incidents (including drug errors). Staff should receive continuing education about the purposes and aims of clinical risk management and incident reporting and consideration should be given to designating specific members of staff with responsibility for reporting.

Reasons for not reporting adverse incidents: an empirical study.

A previous study (Stanhope et al. 1998) established that staff in two obstetric units reported less than a quarter of designated incidents to the units' risk managers. A questionnaire was administered to 42 obstetricians and 156 midwives at the same two obstetric units, exploring the reasons for low rates of reporting. Questions concerned their knowledge of their unit's incident reporting system; whether they would report a series of 10 designated adverse obstetric incidents to the risk manager; and their views on 12 potential reasons for not reporting incidents. Most staff knew about the incident-reporting system in their unit, but almost 30% did not know how to find a list of reportable incidents. Views on the necessity of reporting the 10 designated obstetric incidents varied considerably. For example, 96% of staff stated they would always report a maternal death, whereas less than 40% would report a baby's unexpected admission to the Special Care Baby Unit. Midwives said they were more likely to report incidents than doctors, and junior staff were more likely to report than senior staff. The main reasons for not reporting were fears that junior staff would be blamed, high workload and the belief (even though the incident was designated as reportable) that the circumstances or outcome of a particular case did not warrant a report. Junior doctors felt less supported by their colleagues than senior doctors. Current systems of incident reporting, while providing some valuable information, do not provide a reliable index of the rate of adverse incidents. Recommended measures to increase reliability include clearer definitions of incidents, simplified methods of reporting, designated staff to record incidents and education, feedback and reassurance to staff about the nature and purpose of such systems.

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.

FDG-PET analysis and findings in amnesia resulting from hypoxia.

The assumptions underlying neuroimaging, and problems in its analysis and interpretation, are commonly underestimated in neuropsychology. The ways in which fluoro-deoxy-glucose (FDG) positron emission tomography (PET) data can be analysed are discussed. PET findings from four patients who had suffered severe amnesia, following episodes of acute hypoxia, are presented. These patients had shown evidence of medial temporal (hippocampal and parahippocampal) atrophy on MRI brain scans. The PET data were analysed in several different ways. The converging findings were that the patients showed bilateral thalamic hypometabolism, and there was also evidence of retrosplenial hypometabolism bilaterally. Cognitively, these patients performed most like other patients with medial temporal lesions, but the results indicate that structural lesions can have distal metabolic effects on structures elsewhere. These findings are interpreted in the light of neuroanatomical observations concerning parallel projections between medial temporal lobe structures and the thalamus, some of which pass via the retrosplenium.

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.

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.

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.

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.

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 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.

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.

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.

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.

Memory impairment following ruptured aneurysm of the anterior communicating artery.

This study reports the case of a 42-year-old man who suffered a ruptured aneurysm of the anterior communicating artery. His memory capabilities were assessed after a considerable recovery period during which many of his memory deficits ameliorated. His scan revealed a left frontal lesion and many of his deficits were characteristic of frontal impairment. He was impaired on temporal discrimination, and he showed marked source forgetting. He also performed badly on the Brown-Peterson task, and we suggest that this is another task that may be characteristic of frontal impairment. In contrast, the patient showed normal or near normal performance on some memory tasks but not on others. It is concluded that the patient's frontal signs are similar to those found in Korsakoff's Syndrome, but that his memory impairment is qualitatively different from that encountered in patients with the amnesic syndrome.