Striatal denervation pattern predicts levodopa effects on sequence learning in Parkinson's disease

Mild to moderate Parkinson's disease shows more denervation in the posterodorsal striatum and sparing of the anteroventral striatum. Dopaminergic medications can interfere with anteroventral striatum function by overdosing this relatively intact structure. The authors determined how regional striatal denervation affects medication-associated sequence learning impairment in Parkinson's disease. Eighteen Parkinson's patients performed motor sequence learning on and off levodopa. Patients underwent (11)C-dihydrotetrabenazine positron emission tomography scans to measure nigrostriatal denervation. Patients with more preserved putamen were more likely to exhibit levodopa-associated sequence learning impairments. Furthermore, the ratio of denervation in the anterior to posterior dorsal putamen predicted the level of learning differences on and off levodopa. These results demonstrate that the spatial pattern of nigrostriatal dopaminergic denervation predicts medication responsiveness for motor sequence learning.