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Biomedical subjects

L Cipolotti

Publications and source records attributed to L Cipolotti.

At least 37 records · Page 2Linked to original sources
PubMed2001

Autopsy-confirmed familial early-onset Alzheimer disease caused by the l153V presenilin 1 mutation.

BACKGROUND: Three affected individuals are described from a small English kindred with early-onset autosomal dominant familial Alzheimer disease (FAD) caused by a leucine-to-valine change at codon 153 (L153V) of the presenilin 1 (PSEN1) gene. METHODS: Clinical information on the pedigree was collected directly from family members and from hospital records. Samples of DNA were screened by means of direct sequencing of all coding exons of PSEN1. One patient underwent neuropathological examination. RESULTS: Mean age at onset of symptoms was 35.3 years (95% confidence interval [CI], 34.6-36.0 years); at death, 44.0 years (95% CI, 39.1-48.9 years). Mean duration of illness was 8.3 years (95% CI, 4.7-11.9 years). Myoclonus was a late feature in 1 patient; seizures were not reported in any subjects. Spastic paraparesis and extrapyramidal signs were absent. The neuropsychometric profile of 1 patient showed relatively preserved naming skills in the setting of global cognitive deficits. Results of neuropathological examination demonstrated the signature lesions of Alzheimer disease and the presence of occasional cortical Lewy bodies. CONCLUSIONS: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees.

Adult↗
PubMed2001

Distinct neural systems for the encoding and recognition of topography and faces.

In a series of three positron emission tomography experiments the functional neuroanatomy of four different types of visual stimuli was investigated within the same experimental context. The stimuli were unknown buildings, landscapes, human faces, and animal faces. The purpose of the present study was to compare the stimulus types, both within the same category and across category, by examining if, at encoding (with several seconds exposure to each stimulus) or recognition (over time scales of minutes compared to the seconds of usual perception/one-back studies), common or different neural circuits were activated for all types/categories of stimuli. Within category and although visually very different, the encoding of both buildings and landscapes activated a similar set of brain regions, including bilateral parahippocampal gyrus. This was in contrast to the encoding of both human and animal faces, both of which resulted in activation of the fusiform gyrus bilaterally. Despite the perceptual inputs being identical to those during encoding, the recognition of both buildings and landscapes activated only unilateral right parahippocampal gyrus, while recognition of both human and animal faces activated unilateral right fusiform gyrus. In addition, right superior frontal gyrus and right inferior and medial parietal areas were more active during recognition compared with encoding for all stimulus types. Overall the data identify differential patterns of activation for encoding compared with retrieval of visual stimuli. Furthermore, medial temporal structures specifically are involved in the explicit learning and long-term recognition of topographically relevant stimuli, be they buildings or landscapes, while lateral temporal structures support nontopographical learning and recognition, in this case either human or animal faces.

Adult↗
PubMed2001

Selective impairments for addition, subtraction and multiplication. implications for the organisation of arithmetical facts.

This study reports for the first time a selective impairment for simple addition in patient FS. Moreover, patient VP presented with a selective impairment for simple multiplication and patient DT with a selective impairment for simple subtraction. These findings are discussed in the context of two of the most influential models for the organisation of arithmetical facts in memory (Dehaene and Cohen, 1995, 1997, and Dagenbach and McCloskey, 1992). Dehaene and Cohen (1995, 1997) have proposed that dissociation between arithmetical facts result from a selective impairment to two different types of processing: rote verbal memory for multiplication and simple addition vs. quantity processing for subtraction and division. Dagenbach and McCloskey (1992) suggest dissociation between arithmetical facts result from a selective damage to segregated memory networks specific for each operation. We will argue that our findings are problematic for Dehaene's model and in good accord with McCloskey's view.

Aged↗
PubMed2001

Long-term retrograde amnesia...the crucial role of the hippocampus.

For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.

Aged↗
PubMed2001

The selective preservation of colour naming in semantic dementia.

This paper documents a series of seven patients with semantic dementia who showed a selective preservation in colour naming. This was in the context of a pervasive impairment in naming nouns across a wide range of other semantic categories. To our knowledge, this is the first series of patients with semantic dementia documenting a selective preservation of colour naming. These findings are discussed in the light of current theoretical accounts of category-specific effects and the possible contribution of imageability to this selective preservation of colours.

Aged↗
PubMed2001

Identification without naming: a functional neuroimaging study of an anomic patient.

The neural correlates of identification and name retrieval have proved difficult to characterise because both occur highly automatically in normal language processing. Thus, although some evidence points to the left anterior temporal cortex (ATC) as a brain region underlying these functions, its relative role in semantic and lexical retrieval processes is still a matter of debate. Positron emission tomography (PET) was used to measure regional cerebral blood flow responses to famous and non-famous visually presented faces and buildings in a severely anomic patient and in six control subjects, while they were performing a same-different matching task. Because the patient was able to identify the stimuli that he could not name, it was possible to investigate whether the left ATC would respond when identification occurred without name retrieval. Both the patient and the controls activated the left ATC when famous stimuli were compared with non-famous stimuli. This result supports the hypothesis of a predominantly semantic function of the left ATC.

Adult↗
PubMed2001

Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease.

Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role.

Aged↗
PubMed2000

Category differences in brain activation studies: where do they come from?

Differences in the neural processing of six categories of pictorial stimuli (maps, body parts, objects, animals, famous faces and colours) were investigated using positron emission tomography. Stimuli were presented either with or without the written name of the picture, thereby creating a naming condition and a reading condition. As predicted, naming increased the demands on lexical processes. This was demonstrated by activation of the left temporal lobe in a posterior region associated with name retrieval in several previous studies. This lexical effect was common to all meaningful stimuli and no category-specific effects were observed for naming relative to reading. Nevertheless, category differences were found when naming and reading were considered together. Stimuli with greater visual complexity (animals, faces and maps) enhanced activation in the left extrastriate cortex. Furthermore, map recognition, which requires greater spatio-topographical processing, also activated the right occipito-parietal and parahippocampal cortices. These effects in the visuo-spatial regions emphasize inevitable differences in the perceptual properties of pictorial stimuli. In the semantic temporal regions, famous faces and objects enhanced activation in the left antero-lateral and postero-lateral cortices, respectively. In addition, we showed that the same posterior left temporal region is also activated by body parts. We conclude that category-specific brain activations depend more on differential processing at the perceptual and semantic levels rather than at the lexical retrieval level.

Adult↗
PubMed2000

Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: A clinicopathological study.

We describe 21 affected individuals from a kindred with early-onset autosomal dominant familial Alzheimer's disease caused by an intronic presenilin-1 mutation (in intron 4). Mean age at onset of symptoms was 37.4 years [95% confidence interval (CI): 36.6-38.2 years], mean age at death was 44.7 years (95% CI: 43.1-46.3 years) and mean duration of illness was 7.3 years (95% CI: 5.9-8.7 years). Myoclonus and seizures were prominent features of this pedigree. In the four cases for whom neuropsychometric data were available, verbal memory impairment preceded visual memory deficits; naming was relatively preserved until late in the disease. One of these four cases underwent serial volumetric MRI scans demonstrating in vivo brain tissue loss of 3.9% (38.9 ml, annualized rate of atrophy: 1. 7%) over 22 months of follow-up. The four individuals who had necropsies demonstrated the neuropathological hallmarks of Alzheimer's disease. Apolipoprotein E (APOE) status was assessed in five individuals: the case with the youngest age at onset at 33 years of age was found to be homozygous epsilon4/epsilon4, > 1 SD below the mean age of onset for those of known APOE genotype (36.4 +/- 2.3 years, mean +/- SD), and > 2 SDs below the mean age of onset for the pedigree as a whole (37.4 +/- 1.7 years, mean +/- SD). APOE genotype may therefore modulate age at onset in this pedigree.

Adult↗
PubMed2000

Impaired social response reversal. A case of 'acquired sociopathy'.

In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with 'acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.

Antisocial Personality Disorder↗
PubMed2000

A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems.

MRI was used to measure amygdalar and hippocampal volumes in 14 nondemented depressed patients who persistently complained of "memory" difficulties and in 14 control subjects. Mild neuropsychological impairment had been detected in 5 patients before the study but had later improved. The volume of the left amygdala was smaller in depressed subjects, and there was a trend for smaller left hippocampus in the 5 patients who had exhibited mild cognitive impairment. The authors conclude that subjective memory complaints in depressed patients do not translate into a clinical picture of dementia, but that abnormalities in the amygdala and hippocampus may be relevant in explaining affective and cognitive symptoms.

Adult↗
PubMed1999

Selective sparing of verb naming in a case of severe Alzheimer's disease.

A patient with severe Alzheimer's disease (AD) presented with a severe impairment in naming nouns but selective sparing of the naming of verbs. Her impairment in naming nouns was presented across a wide range of categories investigated. To our knowledge, this is the first case documenting the selective preservation of verb naming in a patient with AD. The implications for the notion of an intrinsic vulnerability of verb naming in AD and for the current knowledge of anatomical correlates of noun/verb processing are discussed.

Aged↗
PubMed1999

Fractionation of visual memory: evidence from a case with multiple neurodevelopmental impairments.

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. However, it is unclear whether these cognitive subsystems can fractionate developmentally. The present study describes an investigation of visual memory of a patient (PE) with multiple developmental disorders. PE was congenitally deaf, had Gilles de la Tourette syndrome and autism, with non-verbal ability in the normal range. The patient presented with a recognition memory impairment for unknown human faces. This contrasted with his superior recognition memory for unknown buildings, landscapes and outdoor scenes. PE's memory impairment for faces could not be explained by a general deficit in face processing. Interestingly, PE also showed a recognition memory impairment for animals. These findings indicate that different domains of the visual memory system can be fractionated developmentally. In particular, it demonstrates that topographical memory can develop independently from other aspects of visual memory.

Adult↗
PubMed1998

Dynamic aphasia: an inability to select between competing verbal responses?

In this study we report a patient (A.N.G.) who, following a malignant left frontal meningioma impinging upon Brodmann area 45, presented a 'pure' dynamic aphasia. Her spontaneous speech was markedly reduced in the absence of any syntactical impairment. Her naming, repetition and reading skills were completely normal. Two experimental investigations were carried out. The first investigation found that A.N.G. had a profound impairment in phrase and sentence generation tasks given a verbal context. However, her verbal generative skills were normal when she was asked to describe pictorial scenes and complex actions. Moreover, it was found that A.N.G. had no difficulty ordering the constituent words of a sentence. Thus, it was concluded that her verbal planning skills were intact. The second investigation tested a hypothesis that dynamic aphasia is due to an inability to select a verbal response option whenever the stimulus activates many competing verbal responses. Predictions based upon this hypothesis were confirmed on three different verbal generation tasks. It was found that our patient's grave verbal generative impairment was present for tasks involving stimuli which activate many potential responses. However, it was absent for tasks involving stimuli which activate few or only a single 'prepotent' response. The findings are discussed with reference to traditional interpretations of dynamic aphasia and more general interpretations of prefrontal cortex functioning. On the basis of a computational model of prefrontal cortex functioning, we propose that pure dynamic aphasia may be caused by damage to a 'context' module containing units responsible for selection of verbal response options. Moreover, it is suggested that our findings support the view that Brodmann area 45 is involved in verbal response generation to stimuli which activate many potential response options.

Aphasia↗
PubMed1998

Selective sparing of topographical memory.

The case of a 61 year old patient with Pick's disease involving predominantly the left temporal lobe, who has been studied over a 5 year period, is reported. She presented with a grave impairment of both verbal and non-verbal memory functions. Her non-verbal memory deficits included profound impairments on the recognition of unfamiliar faces and the recall of abstract designs. Remarkably, her visual recognition memory performance for unknown buildings, landscapes, and outdoor scenes was preserved. Strikingly, her ability to recall familiar routes and learn new ones through a complex virtual reality town was also entirely normal. This seems to be the first case documenting the selective preservation of topographical memory in the context of severe non-verbal and verbal memory impairments. These findings imply that topographical memory and non-verbal memory are subserved by separable neural systems.

Brain↗
PubMed1996

Does recognizing orally spelled words depend on reading? An investigation into a case of better written than oral spelling.

In this study we describe an investigation into the residual spelling skills of a patient (BRK) with a deep dysgraphia. His written spelling was significantly superior to his oral spelling and he had grave difficulties in recognizing orally spelled words. In addition, his impairment in recognizing orally spelled words was qualitatively very similar to his difficulties in oral spelling. In contrast, he could read and repeat the stimuli he could no longer spell. It seems therefore that, recognizing orally spelled words is dependent on the same procedures used in spelling rather than in reading. It is argued that BRK's discrepancy between oral and written spelling reflects a deficit in accessing a letter name code which translates abstract graphemic representations into letter names. In addition, it is suggested that the letter name code has an additional synthesizing function that is involved both in checking self-generated oral spellings and in recognizing orally spelled words.

Aphasia, Wernicke↗
PubMed1996

Topographical disorientation: selective impairment of locomotor space?

We report a single-case study of a patient who suddenly lost her ability to orient herself in her neighbourhood. On formal testing she demonstrated remarkably selective deficits in episodic and semantic memory of topographical items and rouse. Her general intellectual abilities were unaffected as were basic perceptual processes and episodic and semantic memory other than topography. We interpret her deficit as a further example of category-specific processing impairment affecting knowledge acquired through selective channels-in this case visuo-locomotor information.

Brain↗