Biomedical subjects

Jean-Claude Baron

Publications and source records attributed to Jean-Claude Baron.

48 records · Page 3Linked to original sources

PubMed2003

Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment.

The present study aims to unravel, in the same study, both morphological and functional specific substrates of encoding versus retrieval deficits in patients with amnestic mild cognitive impairment (MCI). For this purpose, 21 highly screened MCI patients with isolated memory impairment, who attended a memory clinic and fulfilled operational criteria for MCI, underwent (i) two episodic memory subtests designed to assess preferentially either incidental encoding or retrieval capacity; (ii) a high-resolution T1-weighted volume MRI scan; and (iii) a resting state [18F]fluoro-2-deoxy-D-glucose PET study. Using statistical parametric mapping, positive correlations between memory scores on one hand, and grey matter density and normalized partial volume effect-corrected brain glucose utilization (ncCMRglc) on the other hand, were computed. Deficits in both encoding and retrieval were correlated with declines in hippocampal region grey matter density. The encoding subtest also correlated with hippocampal ncCMRglc, whereas the retrieval subtest correlated with the posterior cingulate area ncCMRglc only. The present findings highlight a distinction in the neural substrates of encoding and retrieval deficits in MCI. Furthermore, they unravel a partial dissociation between metabolic and structural correlates, suggesting distinct interpretations. Hippocampal atrophy was related to both encoding and retrieval deficits, possibly reflecting a direct effect on hippocampal functioning, as well as an indirect effect, through remote functional disruption, on posterior cingulate region synaptic function, respectively.

Aged↗

PubMed2003

Functional neuroimaging studies of motor recovery after stroke in adults: a review.

BACKGROUND: The precise mechanisms of and biological basis for motor recovery after stroke in adults are still largely unknown. Reorganization of the motor system after stroke as assessed by functional neuroimaging is an intriguing but challenging new field of research. Provocative but equivocal findings have been reported to date. SUMMARY OF REVIEW: We present an overview of functional neuroimaging studies (positron emission tomography or functional MRI) of motor tasks in patients recovered or still recovering from motor deficit after stroke. After a brief account of the connectivity of motor systems and the imaging findings in normal subjects, the literature concerning stroke patients is reviewed and discussed, and a general model is proposed. CONCLUSIONS: Both cross-sectional and longitudinal studies have demonstrated that the damaged adult brain is able to reorganize to compensate for motor deficits. Rather than a complete substitution of function, the main mechanism underlying recovery of motor abilities involves enhanced activity in preexisting networks, including the disconnected motor cortex in subcortical stroke and the infarct rim after cortical stroke. Involvement of nonmotor and contralesional motor areas has been consistently reported, with the emerging notion that the greater the involvement of the ipsilesional motor network, the better is the recovery. This hypothesis is supported by the enhanced activity of the ipsilesional primary motor cortex induced by motor training and acute pharmacological interventions, in parallel with improved motor function. Further longitudinal studies assessing the relationships between such changes and actual recovery, as well as manipulating such changes by rehabilitation or pharmacological maneuvers, should provide further information on these fundamental questions. This review closes with some perspectives for future research.

Adult↗

PubMed2003

Efficient principal component analysis for multivariate 3D voxel-based mapping of brain functional imaging data sets as applied to FDG-PET and normal aging.

Principal component analysis (PCA) is a well-known technique for reduction of dimensionality of functional imaging data. PCA can be looked at as the projection of the original images onto a new orthogonal coordinate system with lower dimensions. The new axes explain the variance in the images in decreasing order of importance, showing correlations between brain regions. We used an efficient, stable and analytical method to work out the PCA of Positron Emission Tomography (PET) images of 74 normal subjects using [(18)F]fluoro-2-deoxy-D-glucose (FDG) as a tracer. Principal components (PCs) and their relation to age effects were investigated. Correlations between the projections of the images on the new axes and the age of the subjects were carried out. The first two PCs could be identified as being the only PCs significantly correlated to age. The first principal component, which explained 10% of the data set variance, was reduced only in subjects of age 55 or older and was related to loss of signal in and adjacent to ventricles and basal cisterns, reflecting expected age-related brain atrophy with enlarging CSF spaces. The second principal component, which accounted for 8% of the total variance, had high loadings from prefrontal, posterior parietal and posterior cingulate cortices and showed the strongest correlation with age (r = -0.56), entirely consistent with previously documented age-related declines in brain glucose utilization. Thus, our method showed that the effect of aging on brain metabolism has at least two independent dimensions. This method should have widespread applications in multivariate analysis of brain functional images.

Adult↗

PubMed2003

Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons.

It is classically recognized that regional cerebral glucose consumption (CMRglc), as measured by positron emission tomography (PET) and [18F]-2-fluorodeoxyglucose (FDG), is a precise index of the integrated local neuronal activity. However, despite extensive use of the FDG-PET method, the significance of the measured CMRglc has been little addressed so far. In the present study, we aimed for the first time to test whether resting-state CMRglc is directly related to synaptic density. To this end, we investigated in the baboon the relationships between CMR(glc) and the levels of synaptophysin (SY), a presynaptic protein classically used to assess synaptic density. CMR(glc), measured in vivo by FDG-PET at the resting-state, and SY levels, assessed postmortem by the Western blot technique, were quantified in seven brain areas of five baboons. By applying these two techniques to the same animals, we found significant positive correlations between CMR(glc) and SY levels, across all regions and all animals, as well as within individual baboons. These findings strongly support the hypothesis that resting-state CMR(glc) reflects integrated synaptic activity.

Animals↗

PubMed2003

Early diagnosis of Alzheimer's disease: contribution of structural neuroimaging.

To accurately predict the development of Alzheimer's disease (AD) at its predementia stage would be a major breakthrough from both therapeutic and research standpoints. In this review, our focus is on markers obtained with structural imaging--especially magnetic resonance imaging (MRI)--and on studies of subjects at risk of developing AD. Among the latter, amnestic mild cognitive impairment (MCI) is currently the most commonly accepted reference, and therefore is specially targeted in this review. MCI refers to patients with significant but isolated memory impairment relative to subjects of identical age. Consistent with established histopathological data, structural imaging studies comparing patients with early probable AD to healthy aged subjects have shown that the most specific and sensitive features of AD at this stage are hippocampal and entorhinal cortex atrophy, especially when combined with a reduced volume of the temporal neocortex. MCI patients have significant hippocampal atrophy when compared to aged normal controls. When comparing patients with probable AD to MCI subjects, hippocampal region atrophy significantly extends to the neighboring temporal association neocortex. However, only longitudinal studies of MCI subjects are suited to assess (in a retrospective way) the predictive value of initial atrophy measurements for progression to AD. Few such studies have been published so far and for the most they were based on small samples. Furthermore, the comparison among studies is clouded by differences in both populations studied and MRI methodology used. Nevertheless, comparing the initial MRI data of at-risk subjects who convert to AD at follow-up to those of nonconverters suggests that a reduced association temporal neocortex volume combined with hippocampal or anterior cingulate cortex atrophy may be the best predictor of progression to AD. These data, although still preliminary, are consistent with postmortem studies describing the hierarchical progression of tau lesions in normal aging and early stages of AD, such that damage to the medial temporal lobe and association cortex would account for the memory and nonmemory cognitive impairments, respectively, the combination of which is required to operationally define probable AD. Future research in this field should capitalize on thorough methodology for brain structure delineation, and combine atrophy measurements to cognitive and/or functional imaging data.

Aged↗

PubMed2003

Displacement of primary sensorimotor cortex activation after subcortical stroke: a longitudinal PET study with clinical correlation.

Five patients with left striatocapsular infarction were studied twice with PET during auditory-cued right thumb-index tapping, around 2 months after stroke and again around 8 months after stroke. At PET1 and PET2, the ipsilesional primary sensorimotor (SM1) activation peak Talairach coordinates were compared to those from seven aged-matched healthy controls. At PET1, there was a significant posterior displacement of SM1 activation peak, which confirms a previous report and may represent unmasking/disinhibition of motor representations. Over time, there was no significant change in the coordinates, and no significant correlation between coordinate changes from PET1 to PET2 and concomitant motor recovery. The implications of posterior displacement of SM1 activation peak for recovery therefore remain elusive.

Acoustic Stimulation↗

PubMed2003

Semantic and episodic memory of music are subserved by distinct neural networks.

Numerous functional imaging studies have shown that retrieval from semantic and episodic memory is subserved by distinct neural networks. However, these results were essentially obtained with verbal and visuospatial material. The aim of this work was to determine the neural substrates underlying the semantic and episodic components of music using familiar and nonfamiliar melodic tunes. To study musical semantic memory, we designed a task in which the instruction was to judge whether or not the musical extract was felt as "familiar." To study musical episodic memory, we constructed two delayed recognition tasks, one containing only familiar and the other only nonfamiliar items. For each recognition task, half of the extracts (targets) were presented in the prior semantic task. The episodic and semantic tasks were to be contrasted by a comparison to two perceptive control tasks and to one another. Cerebral blood flow was assessed by means of the oxygen-15-labeled water injection method, using high-resolution PET. Distinct patterns of activations were found. First, regarding the episodic memory condition, bilateral activations of the middle and superior frontal gyri and precuneus (more prominent on the right side) were observed. Second, the semantic memory condition disclosed extensive activations in the medial and orbital frontal cortex bilaterally, the left angular gyrus, and predominantly the left anterior part of the middle temporal gyri. The findings from this study are discussed in light of the available neuropsychological data obtained in brain-damaged subjects and functional neuroimaging studies.

Adult↗

PubMed2003

Post-stroke plastic reorganisation in the adult brain.

Recovery of function after a stroke is attributable to several factors, including events in the first few days (eg, reabsorption of perilesional oedema, tissue reperfusion). However, consistent reorganisation and recovery after a stroke takes weeks or months. In the early stages, recovery from stroke can vary greatly among patients with identical clinical symptoms. Neuroimaging techniques that enable us to assess baseline and task-related functions, and neurophysiological techniques that measure brain function in "real time", can be used to study the recovery of brain lesions after a stroke. In this review, we discuss important neuroimaging and neurophysiological studies of post-stroke brain reorganisation.

Animals↗

PubMed2002

Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment.

We used voxel-based morphometry to comprehensively and objectively map gray matter loss in 22 patients with amnestic mild cognitive impairment, defined as progressive isolated episodic memory decline. Compared with 22 age-matched healthy controls, patients had highly significant gray matter loss predominantly affecting the hippocampal region and cingulate gyri (posterior and subcallosal part of the anterior), and extending into the temporal neocortex. Compared with 16 age-matched patients with mild Alzheimer's disease, gray matter density was significantly preserved in mild cognitive impairment in the posterior association cortex. This pattern of gray matter loss in mild cognitive impairment agrees with but considerably expands upon previous region-of-interest based MRI studies, and is highly consistent with the course of neurofibrillary tangles across aging and Alzheimer's disease.

Aged↗

PubMed2002

The neural basis of intrusions in free recall and cued recall: a PET study in Alzheimer's disease.

This study was designed to map in Alzheimer's disease patients the correlations between resting-state brain glucose utilization measured by PET and the number of intrusions obtained by means of a specially designed episodic memory test separately in free recall and in cued recall. SPM revealed significant negative correlations between the number of intrusions in free recall and the metabolism of the right superior frontal gyrus. For the intrusions in cued recall, the negative correlations concerned the left rhinal cortex. Our findings suggest that intrusions in free recall reflect perturbations in strategic processes and that intrusions in cued recall are triggered by the cue in a relatively automatic manner. Frontal dysfunction would be responsible for the former and rhinal dysfunction for the latter.

Aged↗

PubMed2002

The neural substrates of episodic memory impairment in Alzheimer's disease as revealed by FDG-PET: relationship to degree of deterioration.

In a previous investigation, we raised the hypothesis that in Alzheimer's disease the cerebral structures implicated in episodic memory deficits may differ according to the severity of cognitive impairment. To test this hypothesis, Story Recall test scores and PET measurements of resting cerebral glucose utilization, a measure of synaptic integrity, were obtained in 40 patients. Using SPM96 (statistical parametric mapping 1996), positive correlations between the two sets of data were calculated on a voxel basis, first in the whole patient sample and then separately in the two subgroups of 20 patients differing in Mini-Mental State Examination score, i.e. those with least impaired and those with most impaired performance ('less severe' and 'more severe' subgroups, respectively). In the whole sample, significant correlations (P < 0.05, corrected for multiple tests) involved bilaterally not only several limbic structures (the hippocampal/rhinal cortex regions, posterior cingulate gyrus and retrosplenial cortex) but also, and less expectedly, some temporo-occipital association areas. However, the subgroup analysis disclosed that, in the less severe subgroup, all significant correlations (P < 0.005, uncorrected) were restricted to the parahippocampal gyrus and retrosplenial cortex, in accordance with both the distribution of changes in tau in early Alzheimer's disease and the known involvement of this network in normal and impaired memory function, while in the more severe subgroup they mainly involved the left temporal neocortex, which is known to be implicated in semantic memory. These findings suggest that, when episodic memory is mildly impaired, limbic functions are still sufficient to subserve the remaining performance, whereas with more severe memory deficit resulting from accumulated pathology the neocortical areas that are normally involved in semantic memory are recruited, perhaps as a form of (inadequate) compensatory mechanism.

Aged↗

PubMed2002

Brain glucose hypometabolism after perirhinal lesions in baboons: implications for Alzheimer disease and aging.

The authors previously reported that excitotoxic lesions of both the perirhinal and entorhinal cortices in baboons induce remote neocortical and hippocampal hypometabolism reminiscent of that observed in Alzheimer disease (AD), suggesting that disconnection may play a role in AD. Because the cerebral metabolic rate of glucose (CMR ) was preferentially correlated with perirhinal damage, the area first affected by neurofibrillary tangles in both AD and normal aging, the present series of experiments aimed at assessing the specific metabolic effects of perirhinal lesions. Using PET, CMR was measured before surgery and sequentially over the ensuing 10 months. Compared with sham-operated baboons, perirhinal lesions induced significant-albeit late and transient-CMR decreases in several brain regions, which significantly correlated with histologic damage for some of these regions. Among them, the temporal and hippocampal regions are metabolically affected after extensive rhinal lesions, in early AD, and aging, while the prefrontal region is affected in aging only. Furthermore, in contrast to AD and rhinal lesions, the posterior cingulate cortex was spared. Both the progressive but significant metabolic effects and specific hypometabolic pattern after perirhinal lesions were confirmed by direct comparisons with previous data obtained after combined lesions of both rhinal areas. Thus, although perirhinal damage appears in itself insufficient to induce sustained CMR decreases, it may contribute to the hypometabolic profile of both AD and normal aging, most likely with a stronger contribution in the latter.

Animals↗