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

Sylvain Harquel; Andéol Cadic-Melchior; Takuya Morishita; Lisa Fleury; Adrien Witon; Martino Ceroni; Julia Brügger; Nathalie H Meyer; Giorgia G Evangelista; Philip Egger; Elena Beanato; Pauline Menoud; Dimitri Van de Ville; Silvestro Micera; Olaf Blanke; Bertrand Léger; Jan Adolphsen; Caroline Jagella; Christophe Constantin; Vincent Alvarez; Philippes Vuadens; Jean-Luc Turlan; Andreas Mühl; Christophe Bonvin; Philipp J Koch; Maximilian J Wessel; Friedhelm C Hummel

doi:10.1161/STROKEAHA.123.045174

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

Stroke. 2024 Apr 19. doi: 10.1161/STROKEAHA.123.045174. Online ahead of print.

Authors

Sylvain Harquel^#^{1

2}, Andéol Cadic-Melchior^#^{1

2}, Takuya Morishita^{1

2}, Lisa Fleury^{1

2}, Adrien Witon^{1

2

3}, Martino Ceroni^{1

2}, Julia Brügger^{1

2}, Nathalie H Meyer⁴, Giorgia G Evangelista^{1

2}, Philip Egger^{1

2}, Elena Beanato^{1

2}, Pauline Menoud^{1

2}, Dimitri Van de Ville^{5

6}, Silvestro Micera^{7

8}, Olaf Blanke^{4

9}, Bertrand Léger¹⁰, Jan Adolphsen¹¹, Caroline Jagella¹², Christophe Constantin¹³, Vincent Alvarez¹³, Philippes Vuadens¹⁰, Jean-Luc Turlan¹⁰, Andreas Mühl¹⁰, Christophe Bonvin¹³, Philipp J Koch^{1

2

14}, Maximilian J Wessel^{1

2

15}, Friedhelm C Hummel^{1

2

16}

Affiliations

¹ Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX), École Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland (S.H., A.C.-M., T.M., L.F., A.W., M.C., J.B., G.G.E., P.E., E.B., P.M., P.J.K., M.J.W., F.C.H.).
² Defitech Chair of Clinical Neuroengineering, INX, EPFL Valais, Clinique Romande de Réadaptation, Sion, Switzerland (S.H., A.C.-M., T.M., L.F., A.W., M.C., J.B., G.G.E., P.E., E.B., P.M., P.J.K., M.J.W., F.C.H.).
³ Health-IT, Centre de Service, Hôpital du Valais, Switzerland (A.W.).
⁴ Laboratory of Cognitive Neuroscience, INX and BMI, EPFL, Geneva, Switzerland (N.H.M., O.B.).
⁵ Medical Image Processing Laboratory, INX, EPFL, Geneva, Switzerland (D.V.V.).
⁶ Department of Radiology and Medical Informatics, University of Geneva (UNIGE), Switzerland (D.V.d.V.).
⁷ The Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy (S.M.).
⁸ Bertarelli Foundation Chair in Translational Neuroengineering, INX and Institute of Bioengineering, School of Engineering, Ecole Polytechnique Fédérale de Lausanne (S.M.).
⁹ Department of Neurology, Geneva University Hospital (HUG), Switzerland (O.B.).
¹⁰ Clinique Romande de Réadaptation, Sion, Switzerland (B.L., P.V., J.-L.T., A.M.).
¹¹ Mediclin Reha-Zentrum Plau am See, Germany (J.A.).
¹² Berner Klinik Montana, Switzerland (C.J.).
¹³ Department of Neurology, Hôpital du Valais, Sion, Switzerland (C.C., V.A., C.B.).
¹⁴ Department of Neurology, University of Lübeck, Germany (P.J.K.).
¹⁵ Department of Neurology, Julius-Maximilians-University Würzburg, Germany (M.J.W.).
¹⁶ Clinical Neuroscience, Geneva University Hospital, Switzerland (F.C.H.).

^# Contributed equally.

PMID: 38639087
DOI: 10.1161/STROKEAHA.123.045174

Abstract

Background: 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 transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke.

Methods: Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation.

Results: From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (P_cluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics.

Conclusions: The present results revealed an abnormal motor cortical reactivity in patients with stroke, 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 poststroke is beneficial and promotes neuronal plasticity and recovery.

Keywords: cortical excitability; electroencephalography; evoked potential; motor cortex; transcranial magnetic stimulation; upper extremity.