Levodopa changes brain motor network function during ankle movements in Parkinson's disease.

Bradykinesia-the cardinal symptom in Parkinson's disease (PD)-affects both upper and lower limbs. While several functional imaging studies investigated the impact of levodopa on movement-related neural activity in Parkinson's disease during upper limb movements, analogue studies on lower limb movements are rare. We studied 20 patients with PD (mean age 66.8 ± 7.2 years) after at least 12 h drug withdrawal (OFF-state) and a second time approximately 40 min after oral administration of 200 mg levodopa (ON-state) behaviourally and by functional magnetic resonance imaging (fMRI) at 3 T during externally cued active ankle movements of the more affected foot at fixed rate. Results were compared with that obtained in ten healthy controls (HC) to separate pure pharmacological from disease-related levodopa-induced effects and to allow for interaction analyses. Behaviourally, all patients improved by at least 20 % regarding the motor score of the Unified Parkinson's disease rating scale after levodopa-challenge (mean scores OFF-state: 38.4 ± 10.1; ON-state: 25.5 ± 8.1). On fMRI, levodopa application elicited increased activity in subcortical structures (contralateral putamen and thalamus) in the patients. In contrast, no significant levodopa-induced activation changes were found in HC. The interaction between "PD/HC group factor" and "levodopa OFF/ON" did not show significant results. Given the levodopa-induced activation increases in the putamen and thalamus with unilateral ankle movements in patients with PD but not in HC, we speculate that these regions show the most prominent response to levodopa within the cortico-subcortical motor-circuit in the context of nigrostriatal dysfunction.