Long-Term Improvement in Motor Learning by Transcranial Direct Current Stimulation

OBJECTIVES: Motor practice and use over one session leads to use-dependent plasticity. When practice is repeated over multiple sessions, motor performance continues improving until a plateau in performance, the so-called ceiling effect is reached. This issue is particularly important in neurorehabilitative treatments in which patients usually reach a ceiling effect without further improvement. Thus, it would be desirable to modify ceiling effects in motor rehabilitation. The purpose of this protocol is to determine if repeated applications of TDCS, a form of non-invasive cortical stimulation known to transiently improve performance, in association with training, could elicit additional improvements in motor performance beyond the ceiling effect identified during performance of a visuomotor training task. We will test the hypothesis that anodal TDCS applied over M1 in temporal relation with motor training will lead to more prominent long-term learning of a visuomotor task relative to sham stimulation (which would document the ceiling effect) in healthy individuals and chronic stroke patients and traumatic brain injury (TB1) patients.. STUDY POPULATION: We plan to study 177 healthy volunteers (part 1) and 60 chronic stroke patients (part 2) and 50 TB1 patients with 50 additional healthy volunteers (part 3). Therefore, an overall enrollment of 337 participants is planned. DESIGN: The study will follow a parallel design. Healthy volunteers (part 1) and stroke patients (part 2)will be randomly allocated to one of three groups. Each group will receive anodal TDCS or sham in a fixed time frame related to motor training (during or immediately after motor training). TB1 patients and healthy volunteers (part 3) will be randomly allocated to one of two groups. Each group will receive either sham or anodal tDCS during training. Healthy volunteers and stroke patients will participate in 10 sessions. First, they will train a visuomotor task (VMT) on 5 consecutive days while receiving sham stimulation (group 3) or TDCS during (group 1), or immediately after (group 2) the training. Performance of the VMT will be re-evaluated at 30, 60 and 90 days after the first training session. Traumatic brain injury (TB1) patients and a group of healthy volunteers (part 3) will participate in 6 sessions. First, they will train a visumomotor task (VMT) on 3 consecutive days while receiving anodal tDCS or sham stimulation during the training. Performance of the VMT will be re-evaluated at 30, 60, and 90 days after the first training session. OUTCOME MEASURES: Primary outcome measure will be the percentage change (from baseline to day 8 in healthy volunteers and stroke patients, and from baseline to day 3 in traumatic brain injury) in the total time necessary to complete 15 correct trials of the visuomotor task. Secondary outcome will be accuracy (no. of errors) and timing (speed) variability of force adaptation in the visuomotor task (Celnik, own data), and pinch force at all other time points, including day 5 as a measure of learning over the training period and 3 months as a measure for long-term retention. In the patient group the Jebsen Taylor Test will be used to assess gross motor function. To better understand the mechanisms underlying the proposed behavioral gains, we will use single- and paired pulse transcranial magnetic stimulation (TMS) to identify corticomotor excitability changes. Furthermore the volunteers will answer several questionnaires to evaluate fatigue and mood (PANAS) and perform short neuropsychological control task to control for changes in attention and memory function.