Identifying Large-Scale Brain Networks in Fragile X Syndrome

Supplementary Online Content

Hall SS, Jiang H, Reiss AL, Greicius MD. Identifying large-scale brain networks in fragile X syndrome. JAMA Psychiatry. Published online September 25, 2013. doi:10.1001/jamapsychiatry.2013.247.

eTable 1. Brain regions showing significant group differences in gray matter density following voxel-based morphometry

eTable 2. Brain regions showing significant group differences in fractional amplitude of low- frequency fluctuations

eTable 3. Brain regions showing significant group differences in network connectivity

eFigure. Group-independent component analysis and dual regression results controlled for psychoactive medication status

This supplementary material has been provided by the authors to give readers additional information about their work.

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eTable 1. Brain Regions Showing Significant Group Differences in Gray Matter Density following Voxel-based Morphometry

Comparison Region Side Clust MNI t P Value er coordinates size x y z Controls > FXS central opercular cortex/insular R 2993 66 -16 18 4.63 .0002 cortex postcental gyrus/insular cortex L 1718 -62 -10 14 4.64 .0006 precuneus cortex L 1129 -12 -70 16 5.32 .0002 thalamus R/L 816 -20 -36 6 4.37 .0012 subcallosal cortex R/L 609 0 18 -10 3.92 .0006 angular gyrus R 565 62 -58 24 5.32 .0002 precuneus cortex R 400 14 -62 14 3.64 .0008 cerebellum L 179 -22 -52 -54 4.64 .0014 cerebellum R 112 24 -32 -32 3.73 .0012 juxtapositional lobule cortex R/L 108 10 -16 40 4.66 .0012 precuneus cortex R/L 27 0 -50 66 3.60 .0028 FXS > Controls caudate R/L 2695 6 10 6 5.63 .0002 anterior parahippocampal gyrus L 463 -22 -26 -6 4.65 .0002 parietal operculum cortex L 148 -48 -32 26 3.75 .0012 angular gyrus L 76 -44 -52 58 4.93 .0002 superior parietal lobule L 57 -30 -46 38 4.64 .0006 Note: Peaks derived from raw t scores masked with TFCE, q < .05 FDR corrected images.

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eTable 2. Brain Regions Showing Significant Group Differences in Fractional Amplitude of Low-Frequency Fluctuations

Comparison Region Side Cluster MNI coordinates t P Value size x y z Controls > FXS insular cortex L 3509 -38 20 -8 6.02 .0002 frontal orbital cortex/insular R 3144 32 28 -6 5.11 .0004 cortex precuneus cortex R/L 2101 -2 -74 26 5.14 .0006 anterior cingulate cortex R/L 979 -2 -6 46 5.31 .0006 precentral gyrus L 492 -48 8 30 3.94 .0014 posterior supramarginal gyrus R 366 40 -50 16 4.20 .0026 superior lateral occipital cortex R 315 42 -68 20 4.93 .0002 postcentral gyrus R/L 54 6 -38 66 3.38 .0044 anterior cingulate cortex R/L 36 -10 10 30 2.39 .0032 posterior insular cortex R 22 36 -12 12 2.77 .0022 FXS positively insular cortex L 135 -38 16 -4 6.95 .0002 covaried with IQ FXS negatively cerebellum R 36 38 -78 -18 5.15 .0008 covaried with IQ lingual gyrus R 35 14 -90 -16 4.24 .0006 occipital pole R 30 18 -102 6 6.40 .0006 Note: Peaks for controls > FXS derived from raw t scores masked with TFCE, q < .05 FDR corrected images. Peaks for one sample with IQ covariate derived from raw t scores masked with TFCE, p < .001 uncorrected maps.

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eTable 3. Brain Regions Showing Significant Group Differences in Network Connectivity

Network Comparison Region Side Cluste MNI t P r size coordinates Value x y z Salience Controls > FXS insular cortex L 94 -38 14 4 4.55 .0002 Precuneus Controls > FXS precuneus cortex R/L 1096 -8 -58 24 5.67 .0002 posterior R 145 38 -42 36 4.20 .0002 supramarginal gyrus occipital fusiform L 107 -28 -86 -16 4.88 .0002 gyrus Left Controls > FXS paracingulate L 2240 2 24 38 6.03 .0002 Executive gyrus/inferior frontal Control gyrus superior lateral L 406 -34 -78 30 3.56 .0008 occipital cortex cerebellum R 332 40 -64 -28 3.76 .0014 posterior middle L 231 -58 -30 -10 3.55 .0028 temporal gyrus frontal pole L 154 -26 48 10 3.51 .0008 superior parietal L 120 -46 -40 56 3.96 .0010 lobule Heschl's gyrus L 97 -40 -28 10 3.36 .0016 frontal pole R 49 38 38 18 3.46 .002 lateral occipital cortex L 28 -46 -66 42 2.88 .0036 Language Controls > FXS middle temporal gyrus R 443 58 -46 28 5.89 .0002 posterior L 438 -52 -50 32 4.27 .0002 supramarginal gyrus anterior superior R 42 46 2 -22 5.25 .0002 temporal gyrus inferior frontal gyrus L 24 -50 10 26 3.89 .0014 inferior frontal gyrus R 23 44 12 16 3.97 .0008 Visuospatial Controls > FXS anterior supramarginal L 169 -50 -28 40 5.74 .0002 gyrus posterior cingulate L 150 -10 -26 32 5.12 .0004 gyrus cerebellum L 65 -20 -62 -52 3.92 .0004 posterior cingulate R 37 16 -30 34 4.22 .0008 gyrus cerebellum L 23 -28 -52 -50 4.19 .0008 cerebellum L 22 -6 -58 -10 4.45 .0002 Primary FXS > Controls thalamus L 66 -8 -12 12 5.33 .0002 Visual Note: Peaks derived from raw t scores masked with TFCE, q < .05 FDR corrected images.

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salience right ecn precuneus left ecn language

CONTROLS > FXS

.0001 .01

z = 16 x = -4 y = 18

eFigure. Group-independent component analysis and dual regression results controlled for psychoactive medication status. A) Dual regression results with 17 FXS patients and 16 controls, using presence of medication as a nuisance covariate. All displayed clusters are controls > FXS using TFCE, q < .05 FDR corrected and color coded by network membership. A thalamic cluster in the primary visual network survived the opposite comparison using TFCE, q < .05 FDR corrected (not pictured). B) Fractional amplitude of low-frequency fluctuations between 0.01-0.1 Hz, using TFCE with q < .05 FDR correction, with presence of medication as a nuisance covariate. Blue indicates areas where controls had significantly more faLFF than did patients with FXS. No regions survived multiple comparisons correction for the opposite contrast

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