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

Abstract

AbstractThe neuronal processes sustaining motor recovery after stroke are still largely unknown. Cortical excitation/inhibition dynamics have been suggested previously as a key mechanism occurring after a stroke. Their supportive or maladaptive role immediately after a stroke and during the process of recovery are still not completely understood; it is hypothesized that similar mechanisms (e.g., disinhibition) might yield differential functional roles depending on the stage after the stroke (e.g., acute vs. subacute vs. chronic) and the degree of deficit. Here, we used TMS-EEG to study brain reactivity, motor cortical excitability as well as intracortical inhibition and their impact on residual motor function and recovery longitudinally in a large cohort of stroke patients.EEG responses evoked by TMS applied to the ipsilesional motor cortex (iMC) were acquired in 66 stroke patients in the acute (1-week), sub-acute (3-weeks) and chronic stage (3-months). Readouts of ipsilesional cortical reactivity, excitability and intracortical inhibition were drawn from TMS-evoked potentials and derived metrics. Residual function of the upper limb was quantified through a detailed motor evaluation.A large proportion of patients, especially the most affected ones, exhibited large, simple TMS-evoked neuronal responses. Bayesian correlations revealed a link between higher excitability in iMC in the acute and stronger reduction of impairment determined by the upper extremity Fugl-Meyer (FM-UE) score in the early chronic stage. Furthermore, a decrease of this abnormally large response in the following months was related to better motor recovery. When investigating the underlying mechanisms with a focus on the intracortical GABAergic system, the present results revealed changes in intracortical inhibition in the first week after stroke that were associated with better recovery. Additionally, restoration of intracortical inhibition was present in patients, who recovered the most. Furthermore, the large component observed in a relevant part of the patients masks underlying mechanisms reflecting the importance of changes in intracortical inhibition for successful recovery.The present results strongly support the view of a beneficial role of cortical disinhibition in the first week after a stroke that promotes neuronal plasticity and recovery. However, to sustain long-term motor recovery, cortical disinhibition needs to be transient with crucial restoration of normal levels of intracortical inhibition. TMS-EEG has the exciting potential to provide proxies to better understand underlying mechanisms of stroke revovery, to determine outcome and to help to tailor interventional treatment strategies to each patient based on the brain reactivity status.