Progressive Grey Matter Volume Changes in Patients with Schizophrenia over 6 Weeks of Antipsychotic Treatment and Their Relationship to Clinical Improvement

Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume （GMV） reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex （rMFC, including the anterior cingulate cortex） in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale （PANSS）, and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential pro- cessing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symp- toms of schizophrenia and for making clinical decisions.

Grey-matter volume as a potential feature for the classification of Alzheimer's disease and mild cognitive impairment: an exploratory study

Specific patterns of brain atrophy may be helpful in the diagnosis of Alzheimer＇s disease （AD）. In the present study, we set out to evaluate the utility of grey-matter volume in the classification of AD and amnestic mild cognitive impairment （aMCI） compared to normal control （NC）individuals. Voxel-based morphometric analyses were performed on structural MRIs from 35 AD patients, 27 aMCI patients, and 27 NC participants. A two-sample two-tailed t-test was computed between the NC and AD groups to create a map of abnormal grey matter in AD. The brain areas with significant differences were extracted as regions of interest （ROIs）, and the grey-matter volumes in the ROIs of the aMCI patients were included to evaluate the patterns of change across different disease severities. Next, correlation analyses between the grey-matter volumes in the ROIs and all clinical variables were performed in aMCI and AD patients to determine whether they varied with disease progression. The results revealed significantly decreased grey matter in the bilateral hippocampus/ parahippocampus, the bilateral superior/middle temporal gyri, and the right precuneus in AD patients.The grey-matter volumes with clinical variables were positively correlated Finally, we performed exploratory linear discriminative analyses to assess the classifying capacity of grey-matter volumes in the bilateral hippocampus and parahippocampus among AD, aMCI, and NC. Leave-one-out cross- validation analyses demonstrated that grey-matter volumes in hippocampus and parahippocampus accurately distinguished AD from NC. These findings indicate that grey-matter volumes are useful in the classification of AD.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

Grey matter(GM)alterations may contribute to cognitive decline in individuals with white matter hyperintensities(WMH)but no consensus has yet emerged.Here,we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment(WMH-MCI),43 WMH patients without cognitive impairment,and 55 healthy controls.Both WMH groups showed GM atrophy in the bilateral thalamus,fronto-insular cortices,and several parietal-temporal regions,and the WMH-MCI group showed more extensive and severe GM atrophy.The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients.Furthermore,the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses.These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Voxel-based meta-analysis of grey matter changes in Alzheimer’s disease

Background:Voxel-based morphometry(VBM)using structural brain MRI has been widely used for the assessment of impairment in Alzheimer’s disease(AD),but previous studies in VBM studies on AD remain inconsistent.Objective:We conducted meta-analyses to integrate the reported studies to determine the consistent grey matter alterations in AD based on VBM method.Methods:The PubMed,ISI Web of Science,EMBASE and Medline database were searched for articles between 1995 and June 2014.Manual searches were also conducted,and authors of studies were contacted for additional data.Coordinates were extracted from clusters with significant grey matter difference between AD patients and healthy controls(HC).Meta-analysis was performed using a new improved voxel-based meta-analytic method,Effect Size Signed Differential Mapping(ES-SDM).Results:Thirty data-sets comprising 960 subjects with AD and 1195 HC met inclusion criteria.Grey matter volume(GMV)reduction at 334 coordinates in AD and no GMV increase were found in the current meta-analysis.Significant reductions in GMV were robustly localized in the limbic regions(left parahippocampl gyrus and left posterior cingulate gyrus).In addition,there were GM decreases in right fusiform gyrus and right superior frontal gyrus.The findings remain largely unchanged in the jackknife sensitivity analyses.Conclusions:Our meta-analysis clearly identified GMV atrophy in AD.These findings confirm that the most prominent and replicable structural abnormalities in AD are in the limbic regions and contributes to the understanding of pathophysiology underlying AD.

Substantial subpial cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology?

Aim: Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Much of the complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome. We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of cortical pathology to total demyelinating lesion area in progressive MS. Methods: Twenty-two cases of progressive MS were prepared as whole bi-hemispheric macrosections for histology, immunostaining and quantitative analysis of lesion number and relative area, leptomeningeal inflammation and microglial/macrophage activation. Results: Cortical grey matter demyelination was seen in all cases, which was more extensive than in white and deep grey matter (hippocampus, thalamus and basal ganglia) and accounted for 0.8%-60.2% of the entire measurable cortical ribbon. The pattern of cortical grey matter demyelination was predominantly subpial (mean 90.9%, range 60%-100%, of total cortical grey matter lesion area) and cases with the largest areas of subpial cortical lesions had more and larger deep grey matter lesions, greater numbers of activated microglia/macrophages, both in lesions as well as in normal cortical grey matter, together with elevated leptomeningeal inflammation and lymphoid-like ;structures. White matter lesion area was unchanged when compared with the progressive MS cases with little subpial cortical demyelination. Conclusion: Analysis of whole coronal macrosections reveals cortical demyelination is more extensive than reported by conventional histological methods. Cases of progressive MS with substantial subpial cortical demyelination that is independent of underlying white matter lesion area support the implications that these lesions may in-part arise through different pathogenetic mechanisms. Biomarkers and/or imaging correlates of this subpial pathology are required if we are to fully comprehend the clinical disease process.

Neuroinflammation in cortical and meningeal pathology in multiple sclerosis:understanding from animal models

Multiple sclerosis(MS)is a neurodegenerative and inflammatory disease usually presenting with acute demyelinating events that can start as,or progress to,chronic damage.The development of animal experimental models,specific for each stage of MS will aid in the design of new drugs specific for the different forms of the disease.Animal models of experimental autoimmune encephalomyelitis successfully reflect the pathophysiological mechanisms of the early phases of MS.However,few models resemble the features of the progressive forms of MS such as cortical demyelination and meningeal inflammation.Recently,a few auspicious animal models recapitulating many of the characteristics of progressive MS,aimed at a better understanding of the pathology of these forms of the disease,have been developed.In this review,we will summarize the latest developments in animal models reflecting the cortical and meningeal pathological features of progressive MS,as well as their response to drugs specifically targeting these forms.