Nicola Stanhope

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.

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.

FDG-PET findings in the Wernicke-Korsakoff syndrome.

This study reports FDG-PET findings in Wernicke-Korsakoff patients. Twelve patients suffering amnesia arising from the Korsakoff syndrome were compared with 10 control subjects without alcohol-related disability. Subjects received [18F]-fluorodeoxyglucose (FDG-PET) imaging as well as neuropsychological assessment and high-resolution MR imaging with volumetric analysis. Volumetric MRI analysis had revealed thalamic and mamillary body atrophy in the patient group as well as frontal lobe atrophy with relative sparing of medial temporal lobe structures. Differences in regional metabolism were identified using complementary region of interest (ROI) and statistical parametric mapping (SPM) approaches employing either absolute methods or a reference region approach to increase statistical power. In general, we found relative hypermetabolism in white matter and hypometabolism in subcortical grey matter in Korsakoff patients. When FDG uptake ratios were examined with occipital lobe metabolism as covariate reference region, Korsakoff patients showed widespread bilateral white matter hypermetabolism on both SPM and ROI analysis. When white matter metabolism was the reference covariate; Korsakoff patients showed relative hypometabolism in the diencephalic grey matter, consistent with their known underlying neuropathology, and medial temporal and retrosplenial hypometabolism, interpreted as secondary metabolic effects within the diencephalic-limbic memory circuits. There was also evidence of a variable degree of more general frontotemporal neocortical hypometabolism on some, but not all, analyses.

Rates of forgetting in Alzheimer dementia

Patients diagnosed with Alzheimers 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.

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 patients 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.

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.

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 Korsakoffs syndrome, herpes encephalitis, and focal frontal lesions) as well as healthy controls. RESULTS Patients with Korsakoffs 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 Korsakoffs 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 Alzheimers 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.

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.