Brain oscillatory modes as a proxy of stroke recovery

Stroke is the leading cause of long-term disability, making the search for successful rehabilitation treatment one of the most important public health issues. A better understanding of the neural mechanisms underlying impairment and recovery and the development of associated markers is critical for tailoring treatments to each individual patient with the ultimate goal of maximizing therapeutic outcomes. Here, we used a novel and powerful method consisting of combined transcranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) to analyze TMS-induced brain oscillations in a large cohort of 60 stroke patients from the acute to the early-chronic phase after a stroke. A data-driven parallel factor analysis (PARAFAC) approach to tensor decomposition allowed to detect brain oscillatory modes specifically centered on the θ, α and β frequency bands. In the acute stage, patients presented a general slowdown of these oscillatory modes, highlighting stroke-induced perturbations within thalamocortical processing. Furthermore, low-frequency modes evolved across stroke stages, according to the extent of motor recovery, associated with changes in GABAergic intracortical inhibition. Overall, these longitudinal changes provide novel insights into the ongoing functional reorganization of brain networks after a stroke and the underlying mechanisms. Notably, we propose that the observed α-mode decrease corresponds to a beneficial disinhibition phase between the subacute and early-chronic stages that fosters structural and functional plasticity and facilitates recovery. Monitoring this phenomenon at the individual patient level will provide critical information for phenotyping patients, developing electrophysiological biomarkers and refining therapies based on personalized excitatory/inhibitory neuromodulation using noninvasive or invasive brain stimulation techniques. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by grants from the Personalized Health and Related Technologies (PHRT-#2017-205) of the ETH Domain (CH), the Defitech Foundation (Strike-the-Stroke project, Morges, CH), the SNSF (NIBS-iCog, 320030L_197899 / 1) and the Wyss Center for Bio- and Neuroengineering (WP030; Geneva, CH). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with the Declaration of Helsinki and was approved by Cantonal Ethics Committee Vaud, Switzerland (project number: 2018-01355). Written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data related to this article are available upon reasonable request from the corresponding author.