Motor recovery following ischaemic stroke in humans: insights from transcranial magnetic stimulation and imaging

Recovery of upper limb function after stroke is associated with reorganisation of cortical motor control, but the mechanisms underlying this process in humans remain unclear. We used Transcranial Magnetic Stimulation (TMS) to probe the natural history of neurophysiological reorganisation acutely and chronically after stroke. We then investigated the use of repetitive TMS as an intervention to interact with learning-associated physiological changes, aiming to enhance the rate at which healthy subjects and patients after stroke learn a novel motor task. Physiological measures acquired longitudinally after stroke revealed an immediate shift from intracortical inhibition towards facilitation in both hemispheres. Correlations of intracortical excitability measures with clinical scores emerged by 3 months, suggesting that disinhibition provides access to remote cortical networks which become clinically relevant during this period. A subsequent experiment used paired coil TMS, and concurrent TMS during functional Magnetic Resonance Imaging, to study cortico-cortical interactions after stroke. The contralesional dorsal premotor cortex showed disinhibition in its interaction with the ipsilesional motor cortex and greater motor state-dependent influence on this region in more impaired patients, suggesting a constructive interhemispheric interaction with the affected hemisphere. In healthy subjects the facilitatory effect of Theta Burst Stimulation (TBS) on cortical excitability was enhanced and prolonged by nicotine, but not by levodopa or dextroamphetamine. Using a thumb movement task, TBS successfully enhanced subsequent motor learning but this effect was blocked by nicotine. TBS increased motor variability, which correlated with learning, and also increased the directional dispersion of evoked thumb movements. This suggests a constructive role for motor output variability in this training paradigm. In chronic stroke, either TBS or levodopa accelerated training in a similar task but without improving final performance. Levodopa alone was associated with overnight consolidation. This work supports a potential role for physiological and/or pharmacological interventions as adjuncts to post-stroke therapy