Altered Resting-State Functional Connectivity of the Striatum in Parkinson's Disease after Levodopa Administration

BACKGROUND: Despite improvement in motor symptoms, the effect of dopaminergic medications on cognition in patients with Parkinson’s disease (PD) is less clear. The purpose of this study was to reveal levodopa-induced acute changes in the functional connectivity of the striatum in patients with PD compared with matched untreated patients and healthy volunteers. METHODS: Twenty-two patients with PD underwent functional magnetic resonance imaging both ON and OFF dopamine-replacement therapy on two consecutive days. Twenty-eight normal aging volunteers also did them without taking in levodopa. Three caudate seeds and two putamen seeds were selected to calculate functional connectivity intensity. RESULTS: Motor symptoms measured by UPDRS were significantly worse in PD OFF than PD ON. Decreased functional connectivity in PD OFF compared to controls was detected in the following seed regions: dorsal caudate, ventral putamen and dorsal putamen. Increases in connectivity in PD ON compared to controls were found in the primary and supplementary motor areas and the associative prefrontal and parietal regions, while decreases in anterior cingulate, ventromedial prefrontal cortex, and parahippocampal gyrus. For the ventral striatal seeds, decreased connectivity in PD ON compared to PD OFF was found in the ventromedial prefrontal and orbitofrontal regions, dorsolateral prefrontal regions. For the dorsal striatal seeds, increased connectivity in PD ON compared to PD OFF was observed in the primary and secondary motor areas. CONCLUSION: Our results suggest that levodopa significantly changes the motor and cognitive networks of the cortico-striatal pathways. This knowledge will lead clinicians to survey a broader range of symptoms in determining optimal therapy.