Cerebral and Cerebellar Grey Matter Atrophy in Friedreich Ataxia: The IMAGE-FRDA Study

SUPPLEMENTARY MATERIALS

Louisa P. Selvadurai, BBNSc(Hons)1*, Ian H. Harding, PhD1*, Louise A. Corben, PhD1,2,3, Monique R. Stagnitti, BSc(Hons)1, Elsdon Storey, PhD4, Gary F. Egan, PhD1,5, Martin B. Delatycki, PhD1,2,3,6, Nellie Georgiou-Karistianis, PhD1

1.  School of Psychological Sciences & Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Australia

2.  Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, Australia

3.  Department of Paediatrics, The University of Melbourne, Australia

4.  Department of Medicine, Monash University, Melbourne, Australia

5.  Monash Biomedical Imaging, Monash University, Melbourne, Australia

6.  Clinical Genetics, Austin Health, Melbourne, Australia

*These authors contributed equally to this work.

Corresponding author:

Dr. Ian Harding

Monash Institute of Cognitive and Clinical Neurosciences

18 Innovation Walk

Monash University, VIC, 3800

Australia

Email:

Phone: +61-3-9905-9283

Fax: +61-3-9905-3948

Supplementary Table 1: Cortical Thickness Reductions in the Cerebral Grey Matter in FRDA

relative to Controls

Region (BA) / Size (mm2) / x / y / z / Avg Group Difference (mm) / pFWE
Paracentral Lobule (6) / L / 819 / -6 / -29 / 52 / 0.26 / 0.0002
Paracentral Lobule (6) / R / 658 / 6 / -12 / 56 / 0.23 / 0.0012
Precuneus (31) / R / 982 / 5 / -60 / 27 / 0.23 / 0.0002
Ventrolateral PFC/Anterior Insula (47) / R / 442 / 30 / 25 / -8 / 0.30 / 0.0252
Temporal Pole (38) / L / 672 / -28 / 6 / -40 / 0.34 / 0.001
Temporal Pole (38) / R / 667 / 30 / 10 / -38 / 0.36 / 0.001

x, y, z = MNI coordinates at cluster peak; All clusters, pcorrected < 0.05 using a cluster-forming

threshold of p < 0.01; pFWE = cluster-level family-wise error corrected p-value

Supplementary Table 2: Volume Reductions in the Cerebral Grey Matter in FRDA

relative to Controls

Region (BA) / Size (uL) / x / y / z / tmax / pFWE
Medial Frontal Gyrus (8) / L / 783 / -6 / 20 / 52 / 5.01 / 0.025
Frontal Operculum (6/44) / L / 1663 / -64 / -4 / 24 / 4.65 / 0.027
Frontal Operculum (6/44) / R / 360 / 62 / 12 / 18 / 4.31 / 0.038
Middle Insula (13) / L / 297 / -50 / -8 / 4 / 4.10 / 0.043
Precuneus (7) / L / 38 / -4 / -64 / 56 / 3.34 / 0.049
Cuneus (18) / R / 4360 / 6 / -78 / 0 / 2.95 / <0.001

x, y, z = MNI coordinates at cluster peak; BA = brodmann area tmax = t-statistic at cluster peak; pFWE = family-wise error corrected peak-cluster (TFCE) significance

Supplementary Table 3: Volume Reductions in the Cerebellar

Grey Matter in FRDA relative to Controls

Region / x / y / z / tmax / pFWE
Crus I / L / -20 / -78 / -24 / 5.8 / 0.0002
Lobule VI / L / -6 / -74 / -26 / 5.2 / 0.0002
Lobule VI / R / 20 / -74 / -22 / 5.2 / 0.0002
Lobule VI / R / 14 / -62 / -24 / 5.0 / 0.0002
Crus I / R / 32 / -68 / -26 / 4.9 / 0.0002
Lobule VI / L / -6 / -76 / -14 / 4.9 / 0.0002
Lobule VI / R / 16 / -74 / -16 / 4.9 / 0.0002
Lobule VI / L / -10 / -64 / -26 / 4.8 / 0.0002
Crus II / L / -38 / -60 / -50 / 4.8 / 0.0006
Lobule VI / L / -14 / -70 / -16 / 4.5 / 0.0002
Lobule VI / R / 32 / -58 / -30 / 4.5 / 0.0002
Crus I / L / -26 / -66 / -36 / 4.5 / 0.0002
Crus II / L / -44 / -46 / -46 / 4.5 / 0.0006
Crus II / R / 40 / -64 / -50 / 4.4 / 0.001
Lobule VIIb / R / 8 / -72 / -42 / 4.3 / 0.001
Crus II / R / 38 / -74 / -42 / 4.2 / 0.001
Crus I / R / 46 / -54 / -28 / 4.2 / 0.001
Lobule VIIb / L / -6 / -72 / -40 / 4.2 / 0.001
Lobule V / R / 14 / -46 / -26 / 4.1 / 0.001

x, y, z = MNI coordinates; t = t-statistic; pFWE = family-wise error corrected

peak-cluster (TFCE) significance; Coordinates of all peaks t > 4 are reported.

Anatomical assignment is based on the SUIT atlas.

Supplementary Table 4: Clinical and Behavioural Correlations in the FRDA Cohort

Region / Size (uL) / x / y / z / r / pFWE
FARS (Negative)
Crus I / L / 18091 / -30 / -72 / -26 / 0.68 / 0.006
Crus I / L / -38 / -78 / -28 / 0.64 / 0.006
Lobule VIIb / L / -28 / -62 / -46 / 0.69 / 0.010
Lobule VI / L / -8 / -74 / -14 / 0.62 / 0.012
Crus I / R / 11857 / 34 / -78 / -30 / 0.67 / 0.009
Crus I / R / 40 / -54 / -40 / 0.62 / 0.011
Crus II / R / 24 / -86 / -32 / 0.63 / 0.011
Lobule VI / R / 3407 / 10 / -66 / -8 / 0.68 / 0.015
Lobule V / R / 16 / -56 / -14 / 0.62 / 0.018
GAA1 (Negative)
Lobule VI / R / 659 / 24 / -50 / -20 / 0.62 / 0.036
Speeded Tapping Interval (Negative)
Crus I / L / 18684 / 30 / -76 / -34 / 0.65 / 0.008
Crus II / L / 18 / -72 / -40 / 0.65 / 0.008
Crus I / L / 28 / -64 / -38 / 0.65 / 0.009
Crus I / L / 38 / -66 / -24 / 0.67 / 0.010
Crus II / R / -28 / -64 / -46 / 0.66 / 0.011
Paced Tapping Precision (Positive)
Crus I / R / 13331 / 34 / -72 / -24 / 0.74 / 0.002
Lobule VI / R / 32 / -54 / -36 / 0.64 / 0.007
Lobule VI / R / 26 / -36 / -40 / 0.61 / 0.011
Lobule IX / L / 10604 / -12 / -56 / -52 / 0.71 / 0.006
Lobule VI / L / -28 / -46 / -38 / 0.70 / 0.013
Crus I / L / -32 / -74 / -26 / 0.66 / 0.014
Lobule VIIIb / R / 18 / -58 / -44 / 0.65 / 0.015
Lobule VIIIb / R / 12 / -60 / -54 / 0.63 / 0.016
Lobule VI / L / -24 / -58 / -36 / 0.61 / 0.020

x, y, z = MNI coordinates at cluster peak; rmax = correlation coefficient at

cluster peak; Coordinates of all peaks r >0.6 (t > 4) are reported.

Anatomical assignment is based on the SUIT atlas.

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