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Biomedical subjects

Lisa Cipolotti

Publications and source records attributed to Lisa Cipolotti.

At least 19 recordsLinked to original sources

The hippocampus is required for short-term topographical memory in humans.

The hippocampus plays a crucial role within the neural systems for long-term memory, but little if any role in the short-term retention of some types of stimuli. Nonetheless, the hippocampus may be specialized for allocentric topographical processing, which impacts on short-term memory or even perception. To investigate this we developed performance-matched tests of perception (match-to-sample) and short-term memory (2 s delayed-match-to-sample) for the topography and for the nonspatial aspects of visual scenes. Four patients with focal hippocampal damage and one with more extensive damage, including right parahippocampal gyrus, were tested. All five patients showed impaired topographical memory and spared nonspatial processing in both memory and perception. Topographical perception was profoundly impaired in the patient with parahippocampal damage, mildly impaired in two of the hippocampal cases, and clearly preserved in the other two hippocampal cases (including one with dense amnesia). Our results suggest that the hippocampus supports allocentric topographical processing that is indispensable when appropriately tested after even very short delays, while the presence of the sample scene can allow successful topographical perception without it, possibly via a less flexible parahippocampal representation.

Adult↗

Qualitatively different memory impairments across frontal lobe subgroups.

Recall impairments in patients with lesions to the prefrontal cortex (PFC) have variously been attributed to problems with organisation at encoding, organisation at retrieval and monitoring at retrieval. Neuroimaging and recent theoretical work has associated the left lateral PFC with organisation and strategy production at encoding, and the right lateral PFC with organisation, error detection and monitoring at retrieval. However few lesion studies have been anatomically specific enough to test the direct predictions made by this work. Proactive interference, response to prompting, monitoring and organisational strategies were examined in 34 patients with frontal lobe lesions and 50 healthy controls using a structured verbal recall task, and the fractionation of deficits according to specific frontal lesion site was explored. Recall impairments were observed in the Right Lateral and Medial frontal subgroups. The Medial recall impairment was unaffected by manipulations at encoding or retrieval and was attributed to a "pure" memory deficit arising from disruption of the limbo-thalamic system. The Right Lateral recall impairment was ameliorated by the provision of prompts at retrieval, indicating a strategic retrieval deficit. This intervention also resulted in an unusual pattern of intrusions, namely an increase in proactive interference responses compared with extra-list intrusions. However contrary to predictions no monitoring impairment was found. We offer two explanations for the pattern of performance in the Right Lateral group: failure of a right lateralised error detection and checking system, or an impairment in the active uncued initiation of a supervisory operation.

Adult↗

Fractionation of memory in medial temporal lobe amnesia.

We report a comprehensive investigation of the anterograde memory functions of two patients with memory impairments (RH and JC). RH had neuroradiological evidence of apparently selective right-sided hippocampal damage and an intact cognitive profile apart from selective memory impairments. JC, had neuroradiological evidence of bilateral hippocampal damage following anoxia due to cardiac arrest. He had anomic and "executive" difficulties in addition to a global amnesia, suggesting atrophy extending beyond hippocampal regions. Their performance is compared with that of a previously reported hippocampal amnesic patient who showed preserved recollection and familiarity for faces in the context of severe verbal and topographical memory impairment [VC; Cipolotti, L., Bird, C., Good, T., Macmanus, D., Rudge, P., & Shallice, T. (2006). Recollection and familiarity in dense hippocampal amnesia: A case study. Neuropsychologia, 44, 489-506.] The patients were administered experimental tests using verbal (words) and two types of non-verbal materials (faces and buildings). Receiver operating characteristic analyses were used to estimate the contribution of recollection and familiarity to recognition performance on the experimental tests. RH had preserved verbal recognition memory. Interestingly, her face recognition memory was also spared, whilst topographical recognition memory was impaired. JC was impaired for all types of verbal and non-verbal materials. In both patients, deficits in recollection were invariably associated with deficits in familiarity. JC's data demonstrate the need for a comprehensive cognitive investigation in patients with apparently selective hippocampal damage following anoxia. The data from RH suggest that the right hippocampus is necessary for recollection and familiarity for topographical materials, whilst the left hippocampus is sufficient to underpin these processes for at least some types of verbal materials. Face recognition memory may be adequately subserved by areas outside of the hippocampus.

Aged↗

Bipolar I and bipolar II disorder: cognition and emotion processing.

BACKGROUND: Cognitive impairment may be part of the endophenotype of bipolar disorder (BP), but little is known about patterns and severity of impairment in BP subgroups and their relation to depression. The same applies to deficits in emotion processing known to be present in BP. METHOD: To explore the relationship between depression and impairment in cognition and emotion processing and the differences between BP subgroups, we assessed 36 (25 BP I and 11 BP II) patients using a cognitive battery and a facial emotion recognition task. RESULTS: BP patients were impaired compared to published norms on memory, naming and executive measures (Binomial Single Proportion tests, p<0.05). Cognitive performance was largely unrelated to depression ratings. Surprise recognition was the only emotion processing impairment in BP patients compared to controls (patients' recognition score 75% v. controls' 89%, p=0.024). Patients with higher depression ratings were more impaired in recognizing expressions of anger (t23=2.21, p=0.037). BP II patients were more impaired than BP I patients in IQ, memory and executive measures (Mann-Whitney tests, p<0.05). Depression severity or exposure to medication or electroconvulsive therapy (ECT) did not explain these differences. CONCLUSIONS: We confirm cognitive impairment and an isolated facial emotion processing deficit in BP patients and suggest that these deficits are largely unrelated to depressive symptoms. Our study also provides evidence that cognitive deficits are more severe and pervasive in BP II patients, suggesting that recurrent depressive episodes, rather than mania, may have a more detrimental and lasting effect on cognition.

Adult↗

Attributional style in a case of Cotard delusion.

Young and colleagues (e.g. Young, A. W., & Leafhead, K. M. (1996). Betwixt life and death: case studies of the Cotard delusion. In P. W. Halligan & J. C. Marshall (Eds.), Method in madness: Case studies in cognitive neuropsychiatry. Mahway, NJ: Lawrence Erlbaum Associates.) have suggested that cases of the Cotard delusion (the belief that one is dead) result when a particular perceptual anomaly (caused by a disruption to the affective component of visual recognition) occurs in the context of an internalising attributional style. This hypothesis has not previously been tested directly. We report here an investigation of attributional style in a 24-year-old woman with Cotard delusion ("LU"). LU's attributional style (and that of ten healthy control participants) was assessed using the Internal, Personal and Situational Attributions Questionnaire (Kinderman, P., & Bentall, R. P. (1996). A new measure of causal locus: the internal, personal and situational attributions questionnaire. Personality and Individual Differences, 20(2), 261-264.). LU showed a significantly greater proportion of internalising attributions than the control group, both overall and for negative events specifically. The results obtained thus support an association of Cotard delusion with an internalising attributional style, and are therefore consistent with the account of Young and colleagues. The potential brain basis of Cotard delusion is discussed.

Adult↗

Unconscious processing of Arabic numerals in unilateral neglect.

This study explores the processing of Arabic numerals in three patients with dense left unilateral neglect. Three tasks have been used: a test of visual awareness (is the stimulus on the left, on the right or on both sides?), a number comparison task (is the number larger or smaller than 5?), a number parity judgment task (is the number odd or even?). The test of visual awareness indicated that all three patients were completely unaware of the stimuli presented in the left hemifield. Despite this, the number comparison and number parity judgment tasks clearly indicated that Arabic numerals were unconsciously processed at semantic level (i.e. quantity). These results show that patients with left unilateral neglect can still semantically process Arabic numerals unconsciously.

Adult↗

Dynamic aphasia in progressive supranuclear palsy: a deficit in generating a fluent sequence of novel thought.

We report a patient (KAS) who presented with pure dynamic aphasia in the context of progressive supranuclear palsy (PSP). KAS had the hallmark propositional language impairment in the context of preserved naming, reading, repetition and comprehension skills. The severity of KAS's propositional language deficit was demonstrated to be comparable to other dynamic aphasic patients. Remarkably, despite virtually abolished propositional speech, KAS was unimpaired on word and sentence level generation tasks that required a single response. This dissociation was further investigated on two discourse level generation tasks that required the generation of multiple connected sentences. Quantitative production analysis and novelty measures demonstrated that her performance was extremely reduced and characterised by a lack of novel words and sentences and a tendency to perseverate. This pattern of performance suggests that there may be two subtypes of dynamic aphasia. Patients with the more documented first subtype have language-specific deficits, fail word and sentence level generation tests and have left inferior frontal gyrus lesions. Patients with the second subtype, like KAS, pass word and sentence level generation tests and fail discourse level generation tests. They have a verbal and non-verbal generation deficit and bilateral frontal and subcortical damage. Our findings are discussed with reference to executive functioning accounts of dynamic aphasia and models of speech production. We interpret our patients' impairment as being underpinned by a deficit in one set of mechanisms involved in discourse generation; namely the generation of a fluent sequence of novel thought.

Aphasia↗

Cognitive functioning in orthostatic hypotension due to pure autonomic failure.

Psychophysiological science proposes close interactions between cognitive processes and autonomic responses, yet the consequences of autonomic failure on cognitive functioning have not been documented. This pilot study investigates, for the first time, the cognitive profile of 14 patients with Pure Autonomic Failure (PAF). Each patient was administered a comprehensive battery of neuropsychological tests and neuroimaging investigation. A number of patients (n = 6) presented with cognitive impairment. The two most frequent types of impairment were: deficits of speed and attention, and executive functioning. Impairments of free recall memory, intellectual functioning, nominal and calculation functions were also documented, albeit in a much lower frequency. These cognitive changes were not always associated with white matter abnormalities. We speculate that the cognitive impairments associated with PAF represent consequences of systemic hypotension with cerebral underperfusion. However, a failure in integrated bodily arousal responses during cognitive behaviours may also contribute to some of the observed deficits.

Aged↗

Amnesia and the hippocampus.

PURPOSE OF REVIEW: Long-term memory impairments have great medical significance and a considerable health and economic burden. Understanding their cognitive and neuroanatomical underpinnings is of crucial importance. Severe amnesia is usually observed following bilateral hippocampal pathology. This review addresses the precise role of the hippocampus and related medial temporal lobe structures in amnesia. RECENT FINDINGS: Disagreements exist over whether, following selective hippocampal damage: retrograde amnesia for episodic memories is temporally limited or extensive and ungraded; anterograde amnesia involves both recollective and familiarity processes. It is accepted that material specific impairments follow unilateral medial temporal lobe damage, with verbal and nonverbal memory lateralized to left or right, respectively. Memory for unknown faces, however, may not depend on the hippocampus. Pharmacological studies in animals, with some extension to humans, highlight promising future therapeutic interventions targeting synaptic plasticity modulation. SUMMARY: Despite considerable progress, some issues remain unresolved. The available evidence favours the view, however, that the hippocampus, in conjunction with other cortical areas, is critical for the retrieval of remote episodic memories and for both recollection and familiarity anterograde memory processes. There are as yet no effective pharmacological treatments for medial temporal lobe amnesia, but various rehabilitative techniques may be useful.

Amnesia↗

Impaired allocentric spatial memory underlying topographical disorientation.

The cognitive processes supporting spatial navigation are considered in the context of a patient (CF) with possible very early Alzheimer's disease who presents with topographical disorientation. Her verbal memory and her recognition memory for unknown buildings, landmarks and outdoor scenes was intact, although she showed an impairment in face processing. By contrast, her navigational ability, quantitatively assessed within a small virtual reality (VR) town, was significantly impaired. Interestingly, she showed a selective impairment in a VR object-location memory test whenever her viewpoint was shifted between presentation and test, but not when tested from the same viewpoint. We suggest that a specific impairment in locating objects relative to the environment rather than relative to the perceived viewpoint (i.e. allocentric rather than egocentric spatial memory) underlies her topographical disorientation. We discuss the likely neural bases of this deficit in the light of related studies in humans and animals, focusing on the hippocampus and related areas. The specificity of our test indicates a new way of assessing topographical disorientation, with possible application to the assessment of progressive dementias such as Alzheimer's disease.

Activities of Daily Living↗

Cognitive functioning after medial frontal lobe damage including the anterior cingulate cortex: a preliminary investigation.

Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was compared with age and education matched healthy controls. Both patients showed intact intellectual, memory, and language abilities. No clear-cut abnormalities were noted in visuoperceptual functions. Speed of information processing was mildly reduced only in Patient 2 (bilateral ACC lesion). The patients demonstrated weak or impaired performance only on selective executive function tests. Performance on anterior attention tasks was satisfactory. We tentatively suggest that our findings are inconsistent with anterior attention theories of ACC function based on neuroimaging findings. We propose that the data may imply that the ACC does not have a central role in cognition. We speculate that our findings may be compatible with the view that the ACC integrates cognitive processing with autonomic functioning to guide behaviour.

Adult↗

The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study.

Bilateral hippocampal pathology typically results in significant memory problems. Despite apparently similar structural damage, patients with such lesions can differ in the pattern of impairment and preservation of memory functions. Previously, an fMRI study of a developmental amnesic patient whose anoxic hippocampal damage was incurred perinatally revealed his residual hippocampal tissue to be active during memory retrieval. This hippocampal activity was apparent during the retrieval of personal and general facts relative to a control task. In this study, we used a similar fMRI paradigm to investigate whether residual hippocampal activation was present also in patient VC with adult-acquired anoxic hippocampal pathology. VC's performance and reaction times on the experimental personal and general fact tasks were comparable to age-matched control subjects. However, in contrast to the elderly control sample and the previous developmental amnesic patient, his residual hippocampal tissue did not show activation changes during the experimental tasks. This finding indicates that patient VC's successful retrieval of personal and general facts was achieved without a significant hippocampal contribution. It further suggests that the hippocampal activation observed in the elderly controls and previous developmental amnesic patient was not necessary for successful task performance. The reason for this difference in hippocampal responsivity between VC and the developmental amnesic patient remains to be determined. We speculate that it may relate to the age at which hippocampal damage occurred reflecting plasticity within the developing brain, or to cognitive differences between VC, the developmental amnesic patient, and the control subjects.

Aged↗

Recollection and familiarity in dense hippocampal amnesia: a case study.

In the amnesia literature, disagreement exists over whether anterograde amnesia involves recollective-based recognition processes and/or familiarity-based ones depending on whether the anatomical damage is restricted to the hippocampus or also involves adjacent areas, particularly the entorhinal and perirhinal cortices. So far, few patients with well documented anatomical lesions and detailed assessment of recollective and recognition performance have been described. We report a comprehensive neuroanatomical assessment and detailed investigation of the anterograde memory functions of a previously described severe amnesic patient (VC). The results of four previously published neuroradiological investigations (resting PET, qualitative MRIs, volumetric MRI and functional MRI) together with the results of two new investigations (voxel-based morphometry and magnetic resonance spectroscopy) are presented. The consistent finding across these different qualitative and quantitative examinations of VC's brain has shown that there is primarily structural and functional abnormality located selectively in the hippocampus bilaterally. Marked impairments in both verbal and non-verbal recall and recognition standardized memory tests were documented in the context of VC's intact cognitive profile and normal semantic memory. The results of five new experimental recognition memory tests tapping recollection and familiarity using verbal, topographical (buildings and landscapes) and unknown human faces memoranda revealed striking differential effects according to the type of stimuli used. A receiver operating characteristic analysis revealed that VC's recollective- and familiarity-based recognition processes were well preserved for unknown human faces. In contrast, recollective-based recognition for verbal and topographical material was at floor. Familiarity-based recognition was also impaired, significantly below controls for verbal and buildings memoranda and quite weak, although not reaching significance, for landscapes. These data suggest that the hippocampus is involved in recollective processes of verbal and topographical stimuli. It also plays an appreciable role in familiarity processes for these stimuli. However, recollection and familiarity of human faces appear not to depend on this region.

Aged↗

Sporadic and familial dementia with ubiquitin-positive tau-negative inclusions: clinical features of one histopathological abnormality underlying frontotemporal lobar degeneration.

BACKGROUND: Frontotemporal lobar degeneration comprises a group of diseases with clinical presentations and underlying histopathologies that overlap. Familial disease occurs in up to 50% of frontotemporal lobar degeneration cases. One of several underlying histopathological abnormalities is of ubiquitin-positive tau-negative inclusions, similar to those in motor neuron disease. OBJECTIVE: To compare clinical features of familial and sporadic cases in this pathological subgroup. DESIGN AND PATIENTS: Case note review of dementia patients with ubiquitin-positive tau-negative inclusion pathological abnormalities proven by autopsy. SETTING: United Kingdom tertiary referral center. MAIN OUTCOME MEASURES: Analysis of clinical features. RESULTS: Eleven familial cases (autosomal dominant) and 18 sporadic cases were identified. Most familial case patients presented with behavioral disturbances similar to those seen in sporadic behavioral cases. Semantic dementia was only seen in sporadic cases. Atypical features occurred in a minority. Sporadic and familial behavioral cases showed no differences in age at onset or disease duration. Neuropsychological test results revealed frontal or temporal deficits in most, but unexpected early parietal deficits in 1. CONCLUSIONS: Behavioral features in familial and sporadic cases were similar, but semantic dementia only occurred in sporadic cases. Diagnostic confusion with Alzheimer disease and corticobasal degeneration occurred in some cases.

Age of Onset↗

Does the left inferior parietal lobule contribute to multiplication facts?

We report a single case, who presents with a selective and severe impairment for multiplication and division facts. His ability to retrieve subtraction and addition facts was entirely normal. His brain lesion affected the left superior temporal and to lesser extent in the left middle temporal gyri and the left precentral gyrus extending inferiorly to the pars opercularis of the left frontal lobe. Interestingly, the left supramarginal and angular gyri (SMG/AG) were spared. This finding realised a double dissociation with a previously reported patient, who despite lesions in the SMG/AG did not have a multiplication impairment (van Harskamp et al., 2002). The previously suggested crucial role of the SMG/AG in the retrieval of simple multiplication facts is therefore poorly supported (Cohen et al., 2000; Lee, 2000).

Adult↗

Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI.

Gradient echo T2*-weighted MRI has high sensitivity in detecting cerebral microbleeds, which appear as small dot-like hypointense lesions. Microbleeds are strongly associated with intracerebral haemorrhage, hypertension, lacunar stroke and ischaemic small vessel disease, and have generated interest as a marker of bleeding-prone microangiopathy. Microbleeds have generally been considered to be clinically silent; however, since they are located in widespread cortical and basal ganglia regions and are histologically characterized by tissue damage, we hypothesized that they would cause cognitive dysfunction. We therefore studied patients with microbleeds (n = 25) and a non-microbleed control group (n = 30) matched for age, gender and intelligence quotient. To avoid the confounding effects of coexisting cerebrovascular disease, the groups were also matched for the extent of MRI-visible white matter changes of presumed ischaemic origin, location of cortical strokes, and for the proportion of patients with different stroke subtypes (including lacunar stroke). A battery of neuropsychological tests was used to assess current intellectual function, verbal and visual memory, naming and perceptual skills, speed and attention and executive function. Microbleeds were most common in the basal ganglia but were also found in frontal, parieto-occipital, temporal and infratentorial regions. There was a striking difference between the groups in the prevalence of executive dysfunction, which was present in 60% of microbleed patients compared with 30% of non-microbleed patients (P = 0.03). Logistic regression confirmed that microbleeds (but not white matter changes) were an independent predictor of executive impairment (adjusted odds ratio = 1.32, 95% confidence interval 1.01-1.70, P = 0.04). Patients with executive dysfunction had more microbleeds in the frontal region (mean count 1.54 versus 0.03; P = 0.002) and in the basal ganglia (mean 1.17 versus 0.32; P = 0.048). There was a modest correlation between the number of microbleeds and the number of cognitive domains impaired (r = 0.44, P = 0.03). This study provides novel evidence that microbleeds are associated with cognitive dysfunction, independent of the extent of white matter changes of presumed ischaemic origin, or the presence of ischaemic stroke. The striking effect of microbleeds on executive dysfunction is likely to result from associated tissue damage in the frontal lobes and basal ganglia. These findings have implications for the diagnosis of stroke patients with cognitive impairment, and for the appropriate use of antihypertensive and antiplatelet treatments in these patients.

Aged↗