Stroke recovery-related changes in cortical reactivity based on modulation of intracortical inhibition

Objective Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used TMS-EEG coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in a large cohort of stroke patients. Methods EEG responses evoked by TMS applied to the ipsilesional motor cortex were acquired in 66 stroke patients in the acute (1-week), subacute (3-weeks) and early chronic (3-months) stage. Readouts of cortical reactivity and intracortical inhibition were drawn from TMS-evoked potentials induced by single pulse and paired pulse TMS. Residual function of the upper limb was quantified through a detailed motor evaluation. Results Most affected patients exhibited larger and simpler brain reactivity patterns. Bayesian statistics revealed a link between abnormally high motor cortical excitability in the acute stage and impairment level, while a decrease of excitability in the following months was related to better motor recovery. The investigation of the intracortical GABAergic inhibitory system using paired pulse TMS revealed the presence of a beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. Interpretation The present results revealed an abnormal motor cortical reactivity in stroke patients, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first week post-stroke is beneficial and promotes neuronal plasticity and recovery.