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Patients with chronic stroke often show increased flexor hypertonia in their affected upper limbs. Although an intervention strategy targeting the extensors of the affected upper limb might thus be expected to have benefits for functional recovery, conventional repetitive motor training has limited clinical utility. Recent studies have shown that repetitive transcranial magnetic stimulation could induce motor recovery. The present study tested whether 5 Hz repetitive transcranial magnetic stimulation of the upper-limb area of the primary motor cortex, combined with extensor motor training, had a greater effect on motor recovery than either intervention alone in stroke hemiparesis. Nine patients with chronic subcortical stroke and nine age-matched healthy subjects completed the crossover study. In separate sessions, we examined the single intervention effect of repetitive wrist and finger extension exercises aided by neuromuscular stimulation, the single intervention effect of 5 Hz repetitive transcranial magnetic stimulation and the combined effect of the two interventions. The motor functions were evaluated behaviourally in patients (Experiment 1) and electrophysiologically in healthy subjects (Experiment 2), both before and after the intervention. In addition, we tested the long-term effect by repeating the combined interventions 12 times in patients (Experiment 3). The motor functions were measured again 2 weeks after the end of the repetitive intervention period. In Experiment 1, the combined intervention, but neither of the single interventions, resulted in an improvement of extensor movement (P < 0.0001) and grip power (P < 0.05), along with a reduction of flexor hypertonia (P < 0.01), in their paretic upper limbs. In Experiment 2, only the combined intervention resulted in selective plastic changes of cortico-spinal excitability (P < 0.01), motor threshold (P < 0.001) and silent period (P < 0.01) for the extensors. In Experiment 3, we also confirmed long-term beneficial effects of the combined intervention in patients. These findings indicate that combining motor training with repetitive transcranial magnetic stimulation can facilitate use-dependent plasticity and achieve functional recovery of motor impairments that cannot be attained by either intervention alone. This method could be a powerful rehabilitative approach for patients with hemiparetic stroke. [ABSTRACT FROM PUBLISHER]

Recently, we have developed a new hybrid-rehabilitation combining 5 Hz repetitive transcranial magnetic stimulation and extensor motor training of the paretic upper-limb for stroke patients with flexor hypertonia. We previously showed that the extensor-specific plastic change in M1 was associated with beneficial effects of our protocol ( Koganemaru et al., 2010 ). Here, we investigated whether extensor-specific multiregional brain reorganization occurred after the hybrid-rehabilitation using functional magnetic resonance imaging. Eleven chronic stroke patients were scanned while performing upper-limb extensor movements. Untrained flexor movements were used as a control condition. The scanning and clinical assessments were done before, immediately and 2 weeks after the hybrid-rehabilitation. As a result, during the trained extensor movements, the imaging analysis showed a significant reduction of brain activity in the ipsilesional sensorimotor cortex, the contralesional cingulate motor cortex and the contralesional premotor cortex in association with functional improvements of the paretic hands. The activation change was not found for the control condition. Our results suggested that use-dependent plasticity induced by repetitive motor training with brain stimulation might be related to task-specific multi-regional brain reorganization. It provides a key to understand why repetitive training of the target action is one of the most powerful rehabilitation strategies to help patients. [ABSTRACT FROM AUTHOR]