Brain oscillatory modes as a proxy of stroke recovery

Abstract

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.

Stroke Recovery–Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition

“…Interestingly, such beneficial disinhibition was also found in the present cohort of patients when focusing on late TMS-induced alpha oscillations, 19 which is also a marker of GABAergic system activity. The time course of this disinhibition, that is, between the early and late subacute stages, and spatial localization, that is, more diffused across the brain, differed from the acute and local phenomenon found here.…”

“…Interestingly, such beneficial disinhibition was also found in the present cohort of patients when focusing on late TMS-induced alpha oscillations, 19 which is also a marker of GABAergic system activity. The time course Stroke.…”

“…The time course of this disinhibition, that is, between the early and late subacute stages, and spatial localization, that is, more diffused across the brain, differed from the acute and local phenomenon found here. Taken all together, our results suggest that motor recovery is supported by a disinhibition phase occurring first in the acute stage to promote plastic changes and reorganization of the localized impacted areas, which then spread on a larger scale to allow remote plasticity and network reorganization towards the late subacute stage 5 (see Figure 6 of Harquel et al 19 ).…”

“…7 Here, we longitudinally evaluated (acute to late subacute) a cohort of patients with stroke with TMS-EEG, in the framework of the TiMeS project. 18 The present study specifically focused on the analysis of the TMS-evoked responses and complements the study of TMS-induced oscillations, 19 the results of which will be put into perspective with those of the present study. Complementary TMS-EEG readouts enabled the study of cortical excitability and evoked dynamics from the individuals' brain reactivity, and their association with motor function at each stage and during the process of motor recovery.…”