Parkinson’s disease is a neurodegenerative disorder involving the basal ganglia that results in a host of motor and cognitive deficits. Dopamine-replacement therapy ameliorates some of the hallmark motor symptoms of Parkinson’s disease, but whether these medications improve deficits in response inhibition, a critical executive function for behavioral control, has been questioned. Several studies of Parkinson’s disease patients “on” and “off” (12-h withdrawal) dopaminergic medications suggested that dopamine-replacement therapy did not provide significant response inhibition benefits. However, these studies tended to include patients with moderate-to-advanced Parkinson’s disease, when the efficacy of dopaminergic drugs is reduced compared to early-stage Parkinson’s disease. In contrast, a few recent studies in early-stage Parkinson’s disease report that dopaminergic drugs do improve response inhibition deficits. Based on these findings, we hypothesized that Parkinson’s disease duration interacts with medication status to produce changes in cognitive function. To investigate this issue, we conducted a meta-analysis of studies comparing patients with Parkinson’s disease and healthy controls on tests of response inhibition (50 comparisons from 42 studies). The findings supported the hypothesis; medication benefited response inhibition in patients with shorter disease duration, whereas “off” medication, moderate deficits were present that were relatively unaffected by disease duration. These findings support the role of dopamine in response inhibition and suggest the need to consider disease duration in research of the efficacy of dopamine-replacement therapy on cognitive function in Parkinson’s disease.

Previous diffusion tensor imaging (DTI) studies of Parkinson’s disease (PD) show reduced microstructural integrity of the corpus callosum (CC) relative to controls, although the characteristics of such callosal degradation remain poorly understood. Here, we utilized a longitudinal approach to identify microstructural decline in the entire volume of the CC and its functional subdivisions over 2 years and related the callosal changes to motor symptoms in early-stage PD. The study sample included 61 PD subjects (N = 61, aged 45–82, 38 M & 23 F, H&Y ≤ 2) from the Parkinson’s Progressive Markers Initiative database (PPMI). Whole-brain voxel-wise results revealed significant fractional anisotropy (FA) and mean diffusivity (MD) changes in the CC, especially in the genu and splenium. Using individually drawn CC regions of interest (ROI), our analysis further revealed that almost all subdivisions of the CC show significant decline in FA to certain extents over the two-year timeframe. Additionally, FA seemed lower in the right hemisphere of the CC at both time-points, and callosal FA decline was associated with FA and MD decline in widespread cortical and subcortical areas. Notably, multiple regression analysis revealed that across-subject akinetic-rigid severity was negatively associated with callosal FA at baseline and 24 months follow-up, and the effect was strongest in the anterior portion of the CC. These results suggest that callosal microstructure alterations in the anterior CC may serve as a viable biomarker for akinetic-rigid symptomology and disease progression, even in early PD.