Improvement of Use Dependent Plasticity in Chronic Stroke Patients

OBJECTIVES: There is no universally accepted strategy to promote recovery of motor function after chronic stroke, the main cause of long-term disability among adults. It is desirable to develop strategies to enhance motor training in this patient group. A recent study in stroke patients and healthy volunteers demonstrated that somatosensory nerve stimulation prior to motor training leads to improvements in use-dependent plasticity (UDP), a process thought to underlie recovery of motor function after brain injury (Sawaki et al., unpublished information). Interestingly, the effects of sensory input on cortical plasticity can be enhanced by a single dose of amphetamine. The objective of this protocol is to further enhance the effect that somatosensory nerve stimulation has on motor training by means of pre-medication with amphetamine. This effect over motor training will be measured by the magnitude of training-induced UDP. Our hypothesis is that the amphetamine-enhanced effects of somatosensory nerve stimulation will increase the magnitude of training-induced UDP. STUDY POPULATION: We plan to study 24 patients with chronic strokes and 24 healthy age- and gender matched normal volunteers. DESIGN: All subjects will participate in 5 different randomized sessions on separate days. The first session will be a familiarization with the behavioral tasks. A second experiment will consist of training with no further interventions to obtain baseline UDP changes. In another two sessions, subjects will be premedicated in a blind manner with amphetamine or placebo before administration of somatosensory nerve stimulation followed by motor training to induce UDP. In the last experiment, the participants will be premedicated with amphetamine and will be exposed to sham somatosensory stimulation prior to the motor training to induce UDP. OUTCOME MEASURES: Primary outcome measure will be the magnitude of UDP (training-induced changes in transcranial magnetic stimulation-evoked kinematic responses). Secondary outcome measures are pinch force; and a functional measure of activities of daily life (ADL): Jebsen-Tailor-Test. To better understand the mechanisms underlying the proposed behavioral gains, we will use TMS to identify changes in corticomotor excitability.