Visuomotor paired associative stimulation enhances corticospinal excitability in post-stroke patients with upper-limb hemiparesis

We assess the effectiveness of a visuomotor paired associative stimulation (vm-PAS) protocol targeting the Action Observation Network (AON) in chronic post-stroke patients with upper-limb mild hemiparesis. Vm-PAS consisted of hand-grasping action observation stimuli repeatedly paired with transcranial magnetic stimulation (TMS) pulses over the ipsilesional primary motor cortex (M1). Fifteen post-stroke patients underwent a session of the vm-PAS and, as a control, of the standard excitatory PAS (M1-PAS), during which slow-rate electrical stimulation of the paretic limb was paired with M1-TMS. Before and after each PAS, we assessed corticospinal excitability (CSE), short-interval intracortical inhibition (SICI), and paretic wrist’s voluntary movements. The two protocols induce distinct muscle-specific CSE enhancements: vm-PAS increases motor-evoked potentials (MEPs) recorded from the paretic first dorsal interosseous muscle. Conversely, M1-PAS increases MEPs recorded from the electrically stimulated extensor carpi radialis muscle. Vm-PAS efficacy correlates with hemiparesis chronicity: the higher the time elapsed since the stroke, the greater vm-PAS effects on CSE. Neither protocol affected SICI or wrist movements. Our results suggest that vm-PAS leads to muscle-specific enhancements of CSE in post-stroke patients, highlighting its potential for modulating M1 excitability after stroke. These findings show the efficacy of a cross-modal PAS protocol targeting the AON in an injured motor system.