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Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke

Firdaus Fabrice Hannanu a,b , Thomas A. Zeffiro b,c , Laurent Lamalle a,d,e,f , Olivier Heck g,h , Félix Renard i , Antoine Thuriot i,k , Alexandre Krainik a,d,e,f,g,h , Marc Hommel b,i,j , Olivier Detante b,h,k , Assia Jaillard a,b,i, ⁎, on behalf of the ISIS-HERMES Study Group K. Garambois 1 , M. Barbieux-Guillot 2 , I. Favre-Wiki 2 , S. Grand 3 , J.F. Le Bas 4 , A. Moisan 5 , M.J. Richard 6 , F. De Fraipont 6 , J. Gere 7 , S. Marcel 7 , W. Vadot 8 , G. Rodier 8 , D. Perennou 9 , A. Chrispin 9 , P. Davoine 9 , B. Naegele 2 , P. Antoine 2 , I. Tropres 10 , F. Renard 11 1 Stroke Unit Centre Hospitalier UniversitaireGrenoble Alpes [CHUGA], France 2 Stroke Unit CHUGA, France 3 Neuroradiology CHUGA, France 4 Neuroradiologie CHUGA, France 5 Unité Mixte de Thérapie Cellulaire [UMTC] CHUGA, France 6 UMTC, France 7 Stroke Unit, CH Chambéry, France 8 Stroke Unit, CH Annecy, France 9 Rehabilitation Unit CHUGA, France 10 IRMaGe UGA, France 11 AGEIS-UGA, France a Unité IRM 3T-Recherche- UMS IRMaGe – Centre Hospitalier Universitaire (CHU) Grenoble Alpes, France b Laboratoire MATICE - Pôle Recherche – CHU Grenoble-Alpes, France c Neurometrika, Potomac, MD, United States d IRMaGe - Inserm US-017, France e IRMaGe - CNRS UMS-3552, France f IRMaGe - Université Grenoble-Alpes -, France g Neuroradiologie et IRM-Centre Hospitalier Universitaire Grenoble-Alpes, France h Grenoble Institut des Neurosciences (GIN) Inserm U836-UJF-CEA-CHU, France i AGEIS, EA-UGA 7407 Université Grenoble Alpes, France j Clinatec - CHU Grenoble-Alpes, France k Unité neurovasculaire - CHU Grenoble-Alpes, France

article info Article history: Received 9 November 2016 Received in revised form 9 January 2017 Accepted 22 January 2017 Available online 26 January 2017

abstract   

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Com- pared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cer- ebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), pu- tamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R 2 = 0.85; bootstrap p b 0.001). Baseline motor-FMS alone predicted only 54% of the variance. When baseline motor-FMS was re- moved, the combination of increased activity in ipsilesional MI-BA4a, ipsilesional thalamus, contralesional mid-cingulum, contralesional OP4 and decreased activity in ipsilesional OP1, predicted better motor outcome (djusted-R 2 = 0.96; bootstrap p b 0.001). In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a) and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend, in which OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.