i. supplementary methods

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in both stroke lesion and white matter skeletons (obtained using the TBSS ... In the JHU atlas, the CST is formed by four regions: superior corona radiata, ...

Predictors of motor stroke recovery

ONLINE SUPPLEMENT Sensorimotor network activity predicts motor recovery after moderate to severe stroke

Firdaus Fabrice Hannanu, Thomas A. Zeffiro, Laurent Lamalle, Olivier Heck, Antoine Thuriot, Alexandre Krainik, Marc Hommel, Olivier Detante and Assia Jaillard on behalf of ISIS-HERMES study group. I.

Supplementary methods

II.

Tables (n=6)

III.

Figures (n=3)

I.

SUPPLEMENTARY METHODS

I.A. Diffusion image processing The diffusion-weighted images (DWIs) were preprocessed using Diffusionist software [1]. First, quality assurance was performed visually for each DWI and corrupted images removed. Then eddy-current correction was performed, and the diffusion tensor estimated. Voxel-wise fractional anisotropy (FA) images were constructed from the resulting tensors. The images with right sided lesions were flipped about the y axis so that all lesions were on the left side for analysis. The next step was linear and nonlinear registration transformation to an FA template in MNI152 standard space (www.fmrib.ox.ac.uk/fsl/data/FMRIB58_FA). These transformations were estimated and then performed by incorporating the knowledge of each patient’s lesion using hand-drawn masks. The percentage of the lesioned CST is computed as the ratio of the number of voxels included in both stroke lesion and white matter skeletons (obtained using the TBSS procedure) of the ipsilesional CST divided by the total number of voxels located in the white matter skeleton of the CST. ROI measurements were made from the FA maps based on the JHU atlas (Oishi et al., 2008). In the JHU atlas, the CST is formed by four regions: superior corona radiata, posterior limb of the internal capsule (PLIC), cerebral peduncles and corticospinal tract (i.e. pons). Correlations between damaged CST percent with the clinical motor scores were performed using Pearson's Correlations. They were also introduced in multimodal multiple linear regression models to predict motor performance and recovery measured using the Fugl-Meyer motor score at six months.

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Predictors of motor stroke recovery

I. B. Motor network ROI analysis. To explore the relationship between the sensorimotor network and behavioral outcome, we selected a priori ROIs from the multi-study activity map generated from an active upper limb motor task in our meta-analysis,7 and including other published motor network areas.8-11 12 13-15 ROIs were selected if they were both seen in the meta-analysis and also belonged to the sensorimotor network described in previous work. Accordingly, 17 right and 17 left anatomical ROIs were kept in this study: MI-4a, MI-4p, MI-1, MI-3b, OP1, OP4, BA44, SMA, Midcingulate cortex (MCC), dorsolateral PMC, ventrolateral PMC, insula, putamen, thalamus and cerebellar lobules V; VI,VIIIa (Table S7). The following ROIs were extracted from the SPM Anatomy toolbox derived from the Jülich atlas 16 (http://www.fz-juelich.de/inm/inm1/DE/Forschung/_docs/SPMAnatomyToolbox/SPMAnatomyToolbox_node.html): MI-4a, MI-4p, S1-1, SI-3b, OP1, OP4, BA44 and cerebellar lobules V; VI,VIIIa. The SMA, MCC, insula, PMC, , thalamus and putamen, which are not displayed in the anatomy toolbox, were extracted from the AAL atlas.17 http://www.cyceron.fr/index.php/en/plateformeen/freeware; http://neuro.imm.dtu.dk/wiki/Automated_Anatomical_Labeling MCC, corresponding to the middle one-third of the cingulate gyrus, includes the caudal parts of areas 33, 24, and 32, designated as areas 33', 24’ (or 24c and 24d), and 32'.11, 18 The anatomical ROIs of the PMC and thalamus overlapped several functional motor ROIs. To obtain one ROI per functional area , we used the common overlap between the sensorimotor region active during active upper limb motor task in the meta-analysis 7 and the anatomical ROI using xjview (http://www.alivelearn.net/xjview8/). For example, the anatomical PMC ROI was overlapped with the dorsal PMC cluster of the meta-analysis to obtain the dorsolateral PMC ROI and with the ventrolateral PMC cluster of the meta-analysis to obtain the ventrolateral PMC ROI. Similarly, the anatomical AAL ROI of the thalamus was overlapped with the thalamic cluster of the meta-analysis resulting in a thalamic ROI located within the premotor thalamus or ventral lateral nucleus (VL) of the thalamus.16, 19 From these sources, we selected 17 right and 17 left ROIs including MI-4a, MI-4p, ventral PMC (vPMC), dorsal PMC (dPMC), SMA, SI-1, SI-3b, OP1/SII , OP4, midcingulate cortex (MCC) , inferior frontal gyrus ‘pars opercularis’ (BA44), putamen, premotor thalamus and cerebellar lobules V-VI-VIIIa. ROIs were extracted from the SPM Anatomy Toolbox.16, 20, 21 and ROIs that are not in the Anatomy Toolbox, including the SMA, PMC, MCC, insula and putamen, and yet part of the motor network,10,11, 18 were extracted from the AAL atlas. 17 This procedure led to a set of 34 ipsilesional and contralesional ROIs spanning the sensorimotor network (Table S7). Using these ROIs, we assessed the relationship between passive-FE related brain activity in the ROIs and clinical scores with Pearson bivariate correlations computed between peak ROI Cohen’s d effect sizes and the clinical scores.

II.

Tables S1-S6 2

Predictors of motor stroke recovery Table S1. Patient clinical scores (N=21) NIHSS NIHSS Barthel Rankin mFMS FMS S-FMS PPT NIHSS Barthel Rankin mFMS FMS S-FMS PPT Baseline admission Six months follow-up 1 23 19 15 4 33 130 A 0 8 100 3 94 210 14 6.67 2 21 16 15 4 32 134 15 0 7 75 3 46 159 17 0 3 17 11 60 4 53 165 19 0 4 100 2 73 174 15 10.66 4 22 22 15 4 4 92 0 0 14 85 3 16 57 4 0 5 15 12 45 4 26 134 17 0 8 95 2 38 155 20 0 6 20 20 0 4 13 116 10 0 11 70 3 29 122 23 0 7 15 12 100 3 100 202 NA 5.67 6 100 3 99 221 20 7.5 8 21 16 10 4 31 128 NA 0 12 95 3 53 162 22 0 9 14 13 50 4 19 96 13 0 9 40 4 20 114 24 0 10 15 11 75 3 61 168 16 0 9 95 3 42 132 A 0 11 13 9 90 3 51 174 22 0 2 100 2 78 200 22 3 12 22 23 5 4 8 90 NA 0 19 25 4 13 94 A 0 13 16 11 50 4 34 140 14 0 10 95 3 40 139 10 0 14 17 12 45 4 17 116 10 0 8 85 3 38 125 15 0 15 16 14 25 4 18 117 12 0 7 80 3 39 137 22 0 16 13 12 45 4 20 120 13 0 11 80 3 28 151 24 0 17 12 10 100 3 84 194 16 9.00 5 100 2 90 188 24 12.5 18 9 7 90 2 100 226 24 11.66 3 100 2 100 226 24 12.66 19 11 8 80 3 89 210 19 8.00 3 100 2 99 217 16 10.33 20 17 10 65 4 35 133 16 0 6 95 3 37 129 19 0 21 25 23 10 4 7 88 NA 0 8 90 3 68 173 12 0 Mean 16.86 13.86 47.14 3.67 39.76 141.57 14.75 1.63 8.10 85.95 2.81 54.29 156.43 18.26 3.02 SD 4.30 4.90 33.15 0.58 30.59 40.90 5.54 3.58 3.99 20.10 0.60 29.33 44.09 5.58 4.77 M indicates male. F female. L left hemisphere. R right hemisphere; FMS = Fugl-Meyer Score (max =226) ; mFMS = motor Fugl-Meyer Score subscore (max= 100); S-FMS = Tactile and proprioceptive sensory FMS subscore (max=24). Maximum FMS indicates max imum of performance and no deficit. NA= not assessable (severe aphasia). V1 indicates pre-inclusion visit at one week post stroke. A indicates aphasia limiting sensory assessment. N

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Predictors of motor stroke recovery Table S2. Relationship between total lesion volume, age and sex against clinical scores

Age stroke

Sex

Lesion volume

R

Sig.

t

Sig.

r

Sig.

FMS V1 Motor FMS V1

-.251 -.156

.207 .439

.122 .009

.904 .993

-.539** -.443*

.004 .021

NIHSS V1

.310

.116

-.303

.765

.583**

.001 .022

Barthel V1

-.368

.059

.041

.968

-.438*

Rankin V1

.142

.538

.083

.417

.169

.463

FMS V6 Motor FMS V6

-.254 -.182

.210 .375

.058 .285

.954 .779

-.583** -.490*

.002 .011

NIHSS V6

.276

.163

-.051

.960

.689**

.000

Barthel V6

-.399*

.039

.218

.830

-.539**

.004

.912

.539*

.012

Rankin V6

.158

.494

-.112

*Correlation is significant at the 0.05 level (2-tailed). **Correlation is s ignificant at the 0.01 level (2-tailed). r: Pearson Correlation Coefficient except for Rankin score where a non parametric Spearman test was used with a rho Correlation Coefficient. t= t-test for comparison between males and females. Coefficient except for Rankin score where a non parametric Spearman test was used with a rho Correlation Coefficient. t= t-test for comparison between males and females. FMS indicates the total Fugl Meyer Score (maximum score = 226) and motor FMS the motor Fugl Meyer Score (maximum score = 100).

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Predictors of motor stroke recovery Table S3. Brain activity measures at peaks and clusters related to passive flexion-extension in healthy controls (right wrist) and 21 stroke patients (paretic wrist). A cluster forming threshold of p