Background
Motor memory formation (MMF), the cortical reorganization that accompanies motor training, may play a beneficial role in motor learning and in the functional recovery that follows injury to the central nervous system. However, MMF decreases with age. Dopaminergic activity, which contributes to motor learning and plasticity, experiences a similar decline with natural aging. The purpose of the present study was 1) to determine if pre-medication with levodopa restores MMF in the elderly to levels documented in younger individuals, 2) to evaluate if levodopa pre-medication leads to increased dopamine release in the dorsal striatum during training, as assessed by 11-C-raclopride PET (D2 receptor imaging), and 3) to compare patterns of dopamine release under levodopa pre-medication in normal volunteers and stroke patients.
Methods
Transcranial magnetic stimulation (TMS) was employed to quantify MMF. Eight healthy elderly volunteers and 3 chronic stroke patients underwent two 11-C- raclopride PET sessions, following the administration of either levodopa or placebo. During each session, the subjects performed 30 minutes of motor training with their dominant hand (normal volunteers) or their paretic hand (stroke patients). Baseline and activation raclopride binding potentials (BPs) were assessed for ROIs in the striatum bilaterally for each session.
Results
None of the elderly subjects showed significant MMF with training alone. Levodopa administration led to (a) an increase in training-dependent dopamine release in the contralateral striatum in healthy volunteers and in the ipsilateral striatum in the patient group and (b) an increase in the magnitude of MMF.
Conclusions
Motor training after levodopa pre-medication significantly increases dopamine release during training in the dorsal striatum, compared to the placebo condition. Increased magnitude of MMF in healthy volunteers with levodopa pre-medication is associated with increased release of dopamine in the contralateral striatum during training, indicating that dopamine release may be a crucial factor in the development of MMF. In stroke patients, motor training after levodopa-premedication also leads more striatal dopamine release. However, the increase in dopamine release is much larger in the ipsilateral (contralesional) dorsal striatum. This finding suggests recruitment of contralesional resources after stroke, possibly contributing to recovery of function. We are currently scanning additional subjects to substantiate these results.