Neural substrates underlying stimulation-enhanced motor skill learning after stroke.

Motor skill learning is one of the key components of motor function recovery after stroke, especially recovery driven by neurorehabilitation. Transcranial direct current stimulation can enhance neurorehabilitation and motor skill learning in stroke patients. However, the neural mechanisms underlying the retention of stimulation-enhanced motor skill learning involving a paretic upper limb have not been resolved. These neural substrates were explored by means of functional magnetic resonance imaging. Nineteen chronic hemiparetic stroke patients participated in a double-blind, cross-over randomized, sham-controlled experiment with two series. Each series consisted of two sessions: (i) an intervention session during which dual transcranial direct current stimulation or sham was applied during motor skill learning with the paretic upper limb; and (ii) an imaging session 1 week later, during which the patients performed the learned motor skill. The motor skill learning task, called the 'circuit game', involves a speed/accuracy trade-off and consists of moving a pointer controlled by a computer mouse along a complex circuit as quickly and accurately as possible. Relative to the sham series, dual transcranial direct current stimulation applied bilaterally over the primary motor cortex during motor skill learning with the paretic upper limb resulted in (i) enhanced online motor skill learning; (ii) enhanced 1-week retention; and (iii) superior transfer of performance improvement to an untrained task. The 1-week retention's enhancement driven by the intervention was associated with a trend towards normalization of the brain activation pattern during performance of the learned motor skill relative to the sham series. A similar trend towards normalization relative to sham was observed during performance of a simple, untrained task without a speed/accuracy constraint, despite a lack of behavioural difference between the dual transcranial direct current stimulation and sham series. Finally, dual transcranial direct current stimulation applied during the first session enhanced continued learning with the paretic limb 1 week later, relative to the sham series. This lasting behavioural enhancement was associated with more efficient recruitment of the motor skill learning network, that is, focused activation on the motor-premotor areas in the damaged hemisphere, especially on the dorsal premotor cortex. Dual transcranial direct current stimulation applied during motor skill learning with a paretic upper limb resulted in prolonged shaping of brain activation, which supported behavioural enhancements in stroke patients.