Sami Obaid ^1,2,3,4* Guido Guberman ⁵ Etienne St-Onge ⁶ Emma Campbell ⁷ Manon Edde ⁴ Layton Lamsam ⁸ Alain Bouthillier ³ Alexander G. Weil ^1,9 Alessandro Daducci ¹⁰ François Rheault ¹¹ Dang K. Nguyen ^1,12,2 Maxime Descoteaux ⁴

• ¹ Department of Neurosciences, University of Montreal, Montreal, Canada
• ² University of Montreal Hospital Centre (CRCHUM), Montreal, Quebec, Canada
• ³ Division of Neurosurgery, Department of Surgery, University of Montreal Hospital Center (CHUM), Montreal, Canada
• ⁴ Sherbrooke Connectivity Imaging Lab (SCIL), Sherbrooke University, Sherbrooke, Canada
• ⁵ Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Canada
• ⁶ Neuroimaging and Surgical Technologies Laboratory (NIST), Montreal Neurological Institute (MNI), Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
• ⁷ Department of Psychology, Faculty of Arts and Sciences, University of Montreal, Montreal, Ontario, Canada
• ⁸ Department of Neurosurgery, School of Medicine, Yale University, New Haven, Connecticut, United States
• ⁹ Division of Pediatric Neurosurgery, Department of Surgery, Sainte Justine Hospital, University of Montreal, Montreal, Canada
• ¹⁰ Department of Computer Science, University of Verona, Verona, Veneto, Italy
• ¹¹ Medical Imaging and Neuroimaging (MINi) Lab, Sherbrooke University, Sherbrooke, Canada
• ¹² Division of Neurology, University of Montreal Hospital Center (CHUM), Montreal, Canada

Introduction. Operculo-insular epilepsy (OIE) is a rare condition amenable to surgery in wellselected cases. Despite the high rate of neurological complications associated with OIE surgery, most postoperative deficits recover fully and rapidly. We provide insights into this peculiar pattern of functional recovery by investigating the longitudinal reorganization of structural networks after surgery for OIE in 10 patients. Methods. Structural T1 and diffusion-weighted MRIs were performed before surgery (t0) and at 6 months (t1) and 12 months (t2) postoperatively. These images were processed with an original, comprehensive structural connectivity pipeline. Using our method, we performed comparisons between the t0 and t1 timepoints and between the t1 and t2 timepoints to characterize the progressive structural remodeling. Results. We found a widespread pattern of postoperative changes primarily in the surgical hemisphere, most of which consisted of reductions in connectivity strength (CS) and regional graph theoretic measures (rGTM) that reflect local connectivity. We also observed increases in CS and rGTMs predominantly in regions located near the resection cavity and in the contralateral healthy hemisphere. Finally, most structural changes arose in the first six months following surgery (i.e., between t0 and t1). Discussion. To our knowledge, this study provides the first description of postoperative structural connectivity changes following surgery for OIE. The ipsilateral reductions in connectivity unveiled by our analysis may result from the reversal of seizure-related structural alterations following postoperative seizure control. Moreover, the strengthening of connections in peri-resection areas and in the contralateral hemisphere may be compatible with compensatory structural plasticity, a process that could contribute to the recovery of functions seen following operculo-insular resections for focal epilepsy.