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Biomedical subjects

M Mesulam

Publications and source records attributed to M Mesulam.

16 recordsLinked to original sources
PubMed2005

Primary progressive aphasia: reversed asymmetry of atrophy and right hemisphere language dominance.

Primary progressive aphasia (PPA) is almost always associated with asymmetrical left hemisphere degeneration. The authors report that right hemisphere atrophy in a patient with PPA was associated with atypical right hemisphere dominance for language. This suggests that neuronal damage in PPA is therefore tightly linked to the underlying anatomy of the language network.

Aphasia, Primary Progressive↗
PubMed2004

[Magnetic resonance studies in Alzheimer's dementia. What routine scanning shows].

Magnetic resonance images of the brain acquired in relationship to the commissural plane have been analyzed in twenty cases classified as Probable Alzheimer's disease (Pr. AD). These examinations have been compared to normal aged matched subjects. All examinations have been made in strict correlation with the planes defined by Talairach and Tournoux (1988). The analysis of brain cortical damage was made by evaluating the sulci of the brain mainly on coronal sections correlated with simultaneous image review of the same area on the two other orthogonal planes. In Pr. AD, an asymmetric atrophic pattern was found mainly on the following areas: amygdaloid nucleus, para hippocampal gyrus, hippocampus, areas 22 and 21, temporal pole, insula, dorso frontal cortex, angular gyrus, superior parietal lobule. The primary motor and visual areas were normal in all cases.

Aged↗
PubMed2000

Emotional curiosity: modulation of visuospatial attention by arousal is preserved in aging and early-stage Alzheimer's disease.

Previous studies have shown that Alzheimer's disease, even in its early stages, decreases novelty-seeking behaviors (curiosity) and impairs the shifting of spatial attention to extrapersonal targets. In this study, early-stage probable Alzheimer's disease patients (PRAD) and young and aging controls were shown pairs of visual scenes, some of which contained emotionally-arousing material, while eye movements were recorded under free viewing conditions. In all three subject groups, emotionally-arousing scenes attracted more viewing time and also became the preferential target of the initial visual orientation. Our findings suggest that the arousing properties of sensory stimuli may overcome some of the AD-related impairments in the distribution of attention to extrapersonal targets. These results may have implications for interventions aimed at improving the cognitive symptoms of PRAD.

Adult↗
PubMed1999

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects.

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.

Adult↗
PubMed1999

A large-scale distributed network for covert spatial attention: further anatomical delineation based on stringent behavioural and cognitive controls.

Functional MRI was used to examine cerebral activations in 12 subjects while they performed a spatial attention task. This study applied more stringent behavioural and cognitive controls than previously used for similar experiments: (i) subjects were included only if they showed evidence of attentional shifts while performing the task in the magnet; (ii) the experimental task and baseline condition were designed to eliminate the contributions of motor output, visual fixation, inhibition of eye movements, working memory and the conditional (no-go) component of responding. Activations were seen in all three hypothesized cortical epicentres forming a network for spatial attention: the lateral premotor cortex (frontal eye fields), the posterior parietal cortex and the cingulate cortex. Subcortical activations were seen in the basal ganglia and the thalamus. Although the task required attention to be equally shifted to the left and to the right, eight of 10 subjects showed a greater area of activation in the right parietal cortex, consistent with the specialization of the right hemisphere for spatial attention. Other areas of significant activation included the posterior temporo-occipital cortex and the anterior insula. The temporo-occipital activation was within a region broadly defined as MT+ (where MT is the middle temporal area) which contains the human equivalent of area MT in the macaque monkey. This temporo-occipital area appears to constitute a major component of the functional network activated by this spatial attention task. Its activation may reflect the 'inferred' shift of the attentional focus across the visual scene.

Adult↗
PubMed1997

Accelerated forgetting in association with temporal lobe epilepsy and paraneoplastic encephalitis.

The association between epilepsy and amnesia is studied in patient J.T. who presented with a very unusual pattern of memory loss with retention of information for hours to days but rapid forgetting of information that exceeded this time frame. J.T.'s unusual memory profile was studied with several tests administered over week-long intervals of time. There was evidence that his retention decreased in conjunction with increased seizures. During a trial of paraldehyde, a decrease in seizure frequency was associated with enhanced memory. J.T.'s memory problem was unlike that described in prototypical cases of amnesia. His day-long retention of new information alongside his absolute loss of that information days later is consistent with the idea that consolidation is a process that occurs over lengthy periods of time.

Adult↗
PubMed1994

A potential noninvasive neurobiological test for Alzheimer's disease.

Currently Alzheimer's disease, which affects more than 20 million people worldwide, can only be definitely diagnosed by histological examination of brain tissue obtained at autopsy or biopsy. There is a great need for an early, noninvasive, sensitive, and easily administered diagnostic test of Alzheimer's disease. Here it is reported that patients diagnosed with probable Alzheimer's disease by standard clinical criteria exhibited a marked hypersensitivity in their pupil dilation response to a cholinergic antagonist, tropicamide, placed in their eyes. It was possible to distinguish 18 of 19 individuals (95%) either clinically diagnosed with Alzheimer's disease or classified as suspect Alzheimer's individuals by neuropsychological screening from 30 of 32 normal elderly controls (94%).

Aged↗
PubMed1993

Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease.

A retrospective chart review of clinical symptoms was done for 20 consecutive patients in whom postmortem examination had revealed senile plaques and neurofibrillary tangles in a distribution consistent with Alzheimer's disease. All patients had met clinical diagnostic criteria for probable Alzheimer's disease. On initial examination, 1 to 14 years beyond putative onset of the dementia, all patients displayed at least some memory impairment. In 16 patients, disturbances of attention or recent memory were among the most salient features. In two patients, language disturbances, and in two others, visuospatial deficits, were more prominent than difficulties with memory and attention. On initial examination, 17 of the 20 patients displayed word-finding difficulties, characteristically in the context of a fluent, anomic aphasia. All of the 12 reexamined patients demonstrated progressive, although variable, deterioration. In general, the initial salient deficit remained salient during much of the disease course. Language comprehension was spared in the earlier stages but eventually deteriorated. Severe deficits emerged in all major cognitive domains as the disease reached the terminal stages. Nonfluent aphasias (eg, Broca's aphasia) were not observed even in the advanced stages of the disease.

Aged↗
PubMed1992

Cholinesterases in the amyloid angiopathy of Alzheimer's disease.

Vessels affected by amyloid angiopathy in patients with Alzheimer's disease also displayed intense acetylcholinesterase and butyrylcholinesterase activity when examined by light and electron microscopy. The enzymatic properties of the vessel-bound cholinesterases were identical to those of the cholinesterases associated with senile plaques and neurofibrillary tangles. This cholinesterase activity is of unknown origin but represents one of the very few features common to all the major pathological markers of Alzheimer's disease.

Aged↗
PubMed1991

Differential distribution of a neurofilament protein epitope in acetylcholinesterase-rich neurons of human cerebral neocortex.

The majority of acetylcholinesterase-rich pyramidal neurons in neocortical layers III and V of the human brain displayed intense immunostaining with SMI-32, a monoclonal antibody which recognizes a non-phosphorylated epitope of neurofilament proteins. In contrast, very few of the heteromorphic acetylcholinesterase-rich perikarya embedded in the white matter of the cerebral hemispheres are associated with this type of immunostaining. These two groups of acetylcholinesterase-rich cortical neurons can thus be differentiated not only on the basis of morphology and location but also on the basis of cytochemical signature. The concurrent visualization of SMI-32 immunoreactivity and acetylcholinesterase enzyme activity also showed that SMI-32 immunoreactive neurons can be subdivided into several subgroups on the basis of their perikaryal acetylcholinesterase activity.

Acetylcholinesterase↗
PubMed1990

Competitive substrate inhibition in the histochemistry of cholinesterase activity in Alzheimer's disease.

We used acetylcholine and butyrylcholine to competitively inhibit the cleavage of acetylthiocholine or butyrylthiocholine in plaques and tangles of Alzheimer's disease. Butyrylcholine was much more effective than acetylcholine in reducing the histochemical reaction for acetylcholinesterase not only in neuronal fibers, but also in plaques and tangles. This is in keeping with biochemical data on acetylcholinesterase and supports the existence of true acetylcholinesterase activity within plaques and tangles. However, 2-4 times higher acetylcholine and buturylcholine concentrations were necessary to inhibit the plaque and tangle bound enzyme. Together with the previously reported different pH optima, this suggests that the plaque- and tangle-bound acetylcholinesterase may represent an altered form of this enzyme.

Acetylcholinesterase↗
PubMed1989

Special properties of cholinesterases in the cerebral cortex of Alzheimer's disease.

Selective cholinesterase inhibitors such as BW284C51 and iso-OMPA showed that the plaques and tangles of Alzheimer's disease contain acetylcholinesterase and butyrylcholinesterase activity. In comparison to the cholinesterases of the normal brain, the plaque and tangle-bound cholinesterases in Alzheimer's disease display major shifts in optimum pH and inhibitor sensitivity.

Acetylcholinesterase↗
PubMed1985

Psychiatric manifestations of right hemisphere infarctions.

Five right-handed patients (aged 45 to 78 years) developed acute psychotic disturbances in conjunction with infarcts in the right hemisphere. Their presentation was marked by agitation, inattention, suspiciousness, paranoid delusions, hallucinations, and lack of appropriate concern. Several of these patients initially received primary psychiatric diagnoses. Although neurological findings indicative of right hemisphere involvement could also be elicited, these were generally overshadowed by the more dramatic behavioral alterations. The electroencephalogram and computerized axial tomography were positive in most cases. These cases demonstrate that the possibility of a right hemisphere lesion needs to be entertained in patients who present with an atypical psychotic episode.

Aged↗
PubMedDate not supplied

Neurocognitive networks and selectively distributed processing.

The association cortex of the human brain can be divided into unimodal and transmodal components. Unimodal (modality-specific) cortical areas are subdivided into upstream regions specialized for encoding unitary features of experience and downstream regions which are specialized for encoding composite features. Modality-specific features lead to multimodal knowledge through the mediation of transmodal areas in the brain. These transmodal areas include cortical regions that are conventionally designated as heteromodal, paralimbic and limbic cortex. Contrary to earlier formulations, it is no longer thought that these transmodal areas contain a convergent residue of knowledge. Instead, it appears that the role of these transmodal areas is to contain a road map for the multifocal binding and calling up of distributed information in multiple modalities. Knowledge can thus be encoded in a flexible distributed rather than rigid convergent form. Observations on patients with focal neurological lesions indicate that transmodal areas act like neural hubs (or gateways) for accessing critical domains of knowledge rather than as dedicated centers for specific cognitive functions. In the processes related to memory, a limbic structure such as the hippocampus does not act as a bank for specific memories but as a critical node for accessing distributed information related to recently acquired experience. Damage to a sufficient volume of the limbic system interferes with the coherence of recall and storage even though the constituent fragments of the corresponding experiences may remain stored quite well in other parts of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Cortex↗