Dataset Information

Gray Matter Features of Reading Disability: A Combined Meta-Analytic and Direct Analysis Approach(1,2,3,4).

ABSTRACT: Meta-analysis of voxel-based morphometry dyslexia studies and direct analysis of 293 reading disability and control cases from six different research sites were performed to characterize defining gray matter features of reading disability. These analyses demonstrated consistently lower gray matter volume in left posterior superior temporal sulcus/middle temporal gyrus regions and left orbitofrontal gyrus/pars orbitalis regions. Gray matter volume within both of these regions significantly predicted individual variation in reading comprehension after correcting for multiple comparisons. These regional gray matter differences were observed across published studies and in the multisite dataset after controlling for potential age and gender effects, and despite increased anatomical variance in the reading disability group, but were not significant after controlling for total gray matter volume. Thus, the orbitofrontal and posterior superior temporal sulcus gray matter findings are relatively reliable effects that appear to be dependent on cases with low total gray matter volume. The results are considered in the context of genetics studies linking orbitofrontal and superior temporal sulcus regions to alleles that confer risk for reading disability.

SUBMITTER: Eckert MA

PROVIDER: S-EPMC4724065 | biostudies-literature | 2016 Jan-Feb

REPOSITORIES: biostudies-literature

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Gray Matter Features of Reading Disability: A Combined Meta-Analytic and Direct Analysis Approach(1,2,3,4).

Eckert Mark A MA Berninger Virginia W VW Vaden Kenneth I KI Gebregziabher Mulugeta M Tsu Loretta L

eNeuro 20160123 1

Meta-analysis of voxel-based morphometry dyslexia studies and direct analysis of 293 reading disability and control cases from six different research sites were performed to characterize defining gray matter features of reading disability. These analyses demonstrated consistently lower gray matter volume in left posterior superior temporal sulcus/middle temporal gyrus regions and left orbitofrontal gyrus/pars orbitalis regions. Gray matter volume within both of these regions significantly predic ...[more]

PMID: 26835509

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Project description:OBJECTIVE:Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. METHODS:We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression. RESULTS:SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). INTERPRETATION:This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210-222.

Project description:ImportanceMultiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown.ObjectiveTo understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS.Design, setting, and participantsIn this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014.Main outcomes and measuresVoxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores).ResultsAmong the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations.Conclusions and relevanceThese biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

Dataset Information

Gray Matter Features of Reading Disability: A Combined Meta-Analytic and Direct Analysis Approach(1,2,3,4).

Publications

Gray Matter Features of Reading Disability: A Combined Meta-Analytic and Direct Analysis Approach(1,2,3,4).

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