Background. Stroke often involves primary motor cortex (M1) and its corticospinal (CST) projections. As hand function is critically dependent on these structures, its recovery is often incomplete. Objective. To determine whether impaired hand function in patients with chronic ischemic stroke involving M1 or CST benefits from the enhancing effect of Hebbian-type stimulation (pairing M1 afferent stimulation and M1 activity in a specific temporal relationship) on M1 plasticity and hand function. Methods. In a double-blind, randomized, sham-controlled design, 20 patients with chronic ischemic stroke affecting M1 or CST were randomly assigned to 5 days of hand motor training that was combined with either Hebbian-type (trainingHebb) or sham stimulation (trainingsham) of the lesioned M1. Measures of hand function and task-based M1 functional magnetic resonance imaging (fMRI) activity were collected prior to, immediately following, and 4 weeks after the intervention. Results. Both interventions were effective in improving affected hand function at the completion of training, but only participants in the trainingHebb group maintained functional gains. Changes in hand function and fMRI activity were positively correlated in both ipsilesional and contralesional M1. Compared with trainingsham, participants in the trainingHebb group showed a stronger relationship between improved hand function and changes in M1 functional activity. Conclusions. Only when motor training was combined with Hebbian-type stimulation were functional gains maintained over time and correlated with measures of M1 functional plasticity. As hand dexterity is critically dependent on M1 function, these results suggest that functional reorganization in M1 is facilitated by Hebbian-type stimulation. ClinicalTrials.gov Identifier: NCT01569607.
Keywords: chronic stroke; functional magnetic resonance imaging (fMRI); hand function; neurorehabilitation; transcranial magnetic stimulation (TMS).