PubMed Health⌕ Search

Biomedical subjects

Jacqueline Palace

Publications and source records attributed to Jacqueline Palace.

6 recordsLinked to original sources
PubMed2006

Loss of interhemispheric inhibition in patients with multiple sclerosis is related to corpus callosum atrophy.

Axonal injury and loss in the corpus callosum (CC) is characteristic of the pathology of multiple sclerosis (MS). Functional magnetic resonance imaging (fMRI) potentially allows neurophysiological consequences of this interhemispheric axonal loss to be defined quantitatively. Here we have used 3T fMRI to study the activation in the contralateral primary sensorimotor cortex and deactivation (mediated by transcallosal tracts) in the homologous ipsilateral region in 14 patients with MS and in 14 matched healthy controls during a simple hand-tapping task. Both healthy controls and MS patients showed similar activation in the motor cortex contralateral to the hand moved, but the patients showed a significantly smaller relative deactivation in the ipsilateral motor cortex (P = 0.002). The difference was accounted for by the sub-group of MS patients who previously had impairment of motor function of the hand tested (MS-phd). The CC of the whole patient group was significantly thinner than for the controls (P = 0.001). Atrophy of the CC was correlated with loss of deactivation for the whole patient group (r = -0.50, P = 0.035), but particularly for MS-phd (r = -0.914, P = 0.004). Interhemispheric physiological inhibition thus is impaired in patients with MS, potentially contributing to impairment of motor control. This work suggests one way in which FMRI monitoring of the transcallosal interactions in motor cortex could become a tool for evaluation of therapies that may enhance function in reversibly impaired pathways.

Adult↗
PubMed2005

Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis.

Cognitive dysfunction (affecting particularly attention and working memory) occurs early in patients with multiple sclerosis. Previous studies have focused on identifying potentially adaptive functional reorganization through recruitment of new brain regions that could limit expression of these deficits. However, lesion studies remind us that functional specializations in the brain make certain brain regions necessary for a given task. We therefore have asked whether altered functional interactions between regions normally recruited provide an alternative adaptive mechanism with multiple sclerosis pathology. We used a version of the n-back task to probe working memory in patients with early multiple sclerosis. We applied a functional connectivity analysis to test whether relationships between relative activations in different brain regions change in potentially adaptive ways with multiple sclerosis. We studied 21 patients with relapsing-remitting multiple sclerosis and 16 age- and sex-matched healthy controls with 3T functional MRI. The two groups performed equally well on the task. Task-related activations were found in similar regions for patients and controls. However, patients showed relatively reduced activation in the superior frontal and anterior cingulate gyri (P > 0.01). Patients also showed a variable, but generally substantially smaller increase in activation than healthy controls with greater task complexity, depending on the specific brain region assessed (P < 0.001). Functional connectivity analysis defined further differences not apparent from the univariate contrast of the task-associated activation patterns. Control subjects showed significantly greater correlations between right dorsolateral prefrontal and superior frontal/anterior cingulate activations (P < 0.05). Patients showed correlations between activations in the right and left prefrontal cortices, although this relationship was not significant in healthy controls (P < 0.05). We interpret these results as showing that, while cognitive processing in the task appears to be performed using similar brain regions in patients and controls, the patients have reduced functional reserve for cognition relevant to memory. Functional connectivity analysis suggests that altered inter-hemispheric interactions between dorsal and lateral prefrontal regions may provide an adaptive mechanism that could limit clinical expression of the disease distinct from recruitment of novel processing regions. Together, these results suggest that therapeutic enhancement of the coherence of interactions between brain regions normally recruited (functional enhancement), as well as recruitment of alternative areas or use of complementary cognitive strategies (both forms of adaptive functional change), may limit expression of cognitive impairments in multiple sclerosis.

Adaptation, Psychological↗
PubMed2003

Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study.

Multiple sclerosis is thought to be an autoimmune, inflammatory, cell-mediated disease. However, there is evidence suggesting that autoantibodies could play a role in the pathogenesis of multiple sclerosis. Many studies have looked for antibodies to candidate antigens such as myelin basic protein or myelin-oligodendrocyte glycoprotein, with inconclusive results. In order to determine whether antibodies to cell surface determinants on oligodendrocyte or neuronal cells were present in multiple sclerosis, we used flow cytometry to detect antibody binding to intact cultured human cell lines, comparing sera from multiple sclerosis patients with sera from patients with other inflammatory CNS diseases. Sera from healthy individuals were used to determine a normal range. Significant surface binding of IgG or IgM antibodies to oligodendrocyte precursor (OPC)-derived cell lines was seen in 50% of multiple sclerosis sera with no significant difference between secondary progressive (SPMS) and relapsing-remitting (RRMS) subgroups. In contrast, binding to a neuronal cell line, SK-N-SH, was seen with 70% of SPMS sera compared with 25% of RRMS sera (P < 0.001). No significant difference in antibody binding between multiple sclerosis sera and control sera was seen when OPCs were differentiated or when the cells were permeabilized to expose intracellular antigens. Results from all nine patients with 'benign' multiple sclerosis were indistinguishable from controls. This study represents a systematic approach to begin to define new antigenic targets in multiple sclerosis and demonstrates that antibodies to accessible antigens on the cell surface of both OPCs and neurons are present in some patients. The results lend support to the possibility that autoantibody-mediated processes are important in a subgroup of multiple sclerosis patients. Identification of the cell surface determinants to which the antibodies bind may shed light on new targets for therapeutic intervention.

Adolescent↗
PubMed2003

Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine.

One explanation for the weak relationship between neuropsychological deficits and conventional measures of disease burden in multiple sclerosis is that brain 'plasticity' allows adaptive reorganization of cognitive functions to limit impairment, despite injury. We have tested this hypothesis. Ten patients with multiple sclerosis and 11 healthy controls were studied using a functional MRI (fMRI) counting Stroop task. The two subject groups had comparable performances, but a predominantly left medial prefrontal region [Brodmann area (BA) 8/9/10] was more active during the task in patients than in controls (corrected P < 0.001), while a right frontal region (including BA 45 and the basal ganglia) was more active in controls than in patients (corrected P = 0.004). The magnitude of the differences correlated with the normalized brain parenchymal volume, a measure of disease burden (r = -0.72, P = 0.02). We then tested the effects of acute administration of rivastigmine, a central cholinesterase inhibitor, on patterns of brain activation. In five out of five multiple sclerosis patients there was a relative normalization of the abnormal Stroop-associated brain activation, although no change in the patterns of brain activation was found in any of four healthy controls given the drug and tested in the same way. We suggest that recruitment of medial prefrontal cortex is a form of adaptive brain plasticity that compensates, in part, for relative deficits in processing related to the reduced right prefrontal cortex activity with multiple sclerosis. This functional plasticity is modulated by cholinergic agonism and must arise from potentially highly dynamic mechanisms such as the 'unmasking' of latent pathways.

Adult↗
PubMed2002

Thalamic neurodegeneration in multiple sclerosis.

Multiple sclerosis is still regarded primarily as a disease of the white matter. However, recent evidence suggests that there may be significant involvement of gray matter. Here, we have used magnetic resonance imaging and magnetic resonance spectroscopy in vivo and histopathology postmortem to estimate thalamic neuronal loss in patients with multiple sclerosis. Our results show that neuronal loss in multiple sclerosis can be substantial (30-35% reduction). We conclude that a neurodegenerative pathology may make a major contribution to the genesis of symptoms in multiple sclerosis.

Adult↗