Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia

FMRIB Centre, Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Brain (Impact Factor: 9.2). 10/2007; 130(Pt 9):2375-86. DOI: 10.1093/brain/awm184
Source: PubMed


Adolescent-onset schizophrenia provides an exceptional opportunity to explore the neuropathology of schizophrenia free from the potential confounds of prolonged periods of medication and disease interactions with age-related neurodegeneration. Our aim was to investigate structural grey and white matter abnormalities in adolescent-onset schizophrenia. Whole-brain voxel-wise investigation of both grey matter topography and white matter integrity (Fractional Anisotropy) were carried out on 25 adolescent-onset schizophrenic patients and 25 healthy adolescents. We employed a refined voxel-based morphometry-like approach for grey matter analysis and the recently introduced method of tract-based spatial statistics (TBSS) for white matter analysis. Both kinds of studies revealed widespread abnormalities characterized by a lower fractional anisotropy neuroanatomically associated with localized reduced grey matter in the schizophrenic group. The grey matter changes can either be interpreted as the result of a locally reduced cortical thickness or as a manifestation of different patterns of gyrification. There was a widespread reduction of anisotropy in the white matter, especially in the corpus callosum. We speculate that the anisotropy changes relate to the functional changes in brain connectivity that are thought to play a central role in the clinical expression of the disease. The distribution of grey matter changes was consistent with clinical features of the disease. For example, grey and white matter abnormalities found in the Heschl's gyrus, the parietal operculum, left Broca's area and the left arcuate fasciculus (similar to previous findings in adult-onset schizophrenia) are likely to relate to functional impairments of language and auditory perception. In addition, in contrast to earlier studies, we found striking abnormalities in the primary sensorimotor and premotor cortices and in white matter tracts susbserving motor control (mainly the pyramidal tract). This novel finding suggests a new potential marker of altered white matter maturation specific to adolescent-onset schizophrenia. Together, our observations suggest that the neuropathology of adolescent-onset schizophrenia involves larger and widespread changes than in the adult form, consistent with the greater clinical severity.

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Available from: Anthony James, Sep 30, 2015
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    • "Surface maps were resampled and mapped to a common coordinate system (fsaverage5, 10,242 vertices) using a non-rigid high-dimensional spherical averaging method to align cortical folding patterns (Fischl et al., 1999). FSL-VBM (Douaud et al., 2007), a voxel-based morphometry (VBM) analysis (Ashburner and Friston, 2000; Good et al., 2001), was used to derive a gray matter volume (GMV) map. The registered map was divided by the Jacobian map of the deformation field to account for local contraction and expansion. "
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    ABSTRACT: Schizophrenia (SZ) is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC). Utilizing linked independent component analysis (LICA), a data-driven multimodal analysis approach, we investigated structure–function associations in a large sample of SZ (n = 96) and HC (n = 142). We tested for associations between task-positive (fronto-parietal) and task-negative (default-mode) brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p b .05, corrected for multiple comparisons) was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure–function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.
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    • "In order to verify the typical pattern of atrophy in AD patients , we evaluated gray matter ( GM ) volume differences between HC and AD . Structural data were analyzed with FSL - VBM ( Douaud et al . , 2007 ) , an optimized VBM protocol ( Good et al . , 2001 ) carried out with FSL . First , structural images were brain - extracted and gray matter - segmented before being registered to the MNI 152 standard space using non - linear registration . The resulting images were averaged and flipped along the x - axis to create a left - right symme"
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    ABSTRACT: Artifact removal from resting state fMRI data is an essential step for a better identification of the resting state networks and the evaluation of their functional connectivity (FC), especially in pathological conditions. There is growing interest in the development of cleaning procedures, especially those not requiring external recordings (data-driven), which are able to remove multiple sources of artifacts. It is important that only inter-subject variability due to the artifacts is removed, preserving the between-subject variability of interest—crucial in clinical applications using clinical scanners to discriminate different pathologies and monitor their staging. In Alzheimer's disease (AD) patients, decreased FC is usually observed in the posterior cingulate cortex within the default mode network (DMN), and this is becoming a possible biomarker for AD. The aim of this study was to compare four different data-driven cleaning procedures (regression of motion parameters; regression of motion parameters, mean white matter and cerebrospinal fluid signal; FMRIB's ICA-based Xnoiseifier—FIX—cleanup with soft and aggressive options) on data acquired at 1.5 T. The approaches were compared using data from 20 elderly healthy subjects and 21 AD patients in a mild stage, in terms of their impact on within-group consistency in FC and ability to detect the typical FC alteration of the DMN in AD patients. Despite an increased within-group consistency across subjects after applying any of the cleaning approaches, only after cleaning with FIX the expected DMN FC alteration in AD was detectable. Our study validates the efficacy of artifact removal even in a relatively small clinical population, and supports the importance of cleaning fMRI data for sensitive detection of FC alterations in a clinical environment.
    Frontiers in Human Neuroscience 08/2015; 9. DOI:10.3389/fnhum.2015.00449 · 2.99 Impact Factor
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    • "Structural data were analyzed using VBM in FSL ( Douaud et al . , 2007 ) , with the following steps . First , T1 - weighted structural images were brain - extracted , regions identified as WMH , deduced on the basis of coregistered FLAIR image , were replaced with simulated normal - appearing WM values to prevent misclassification as GM . Images were GM - segmented and registered to the MNI 152 standard sp"
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    ABSTRACT: Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2-70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden.
    Frontiers in Aging Neuroscience 07/2015; 7:131. DOI:10.3389/fnagi.2015.00131 · 4.00 Impact Factor
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