Promoting motor recovery after stroke using cortico-cortical paired associative stimulation

Stroke is the most prevalent neurological disorder, the primary cause of long-term disability, and the second leading cause of mortality. Post-stroke motor symptoms critically impact and limit stroke survivors' quality of life. Rehabilitation aims to restore motor function by promoting neuroplasticity and neuronal reorganisation. A promising therapeutic approach involves combining non-invasive brain stimulation (NIBS) with activity-based training to enhance neuroplasticity. NIBS are thought to promote the innate neuronal reorganisation of the functionally relevant networks after a stroke. Amongst NIBS techniques, a pioneering method, often referred to as cortico-cortical paired associative stimulation (ccPAS), allows to enhance neuroplasticity in cortical networks. Unlike traditional approaches, ccPAS enables the manipulation of interregional connectivity within specific cortical pathways. In particular, ccPAS can promote synaptic plasticity and connectivity in a functionally relevant cortico-cortical route tailoring the interventions to individual lesion-specific network alterations. In this viewpoint, we propose and critically evaluate the use of ccPAS as a therapeutic tool using upper-limb motor rehabilitation as a primary example, highlighting its potential for post-stroke recovery. We summarise the limited and contrasting evidence supporting the use of ccPAS after a stroke and make suggestions to overcome the current limitations emphasising the need for further future research.