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Effect of levodopa on fronto-parietal network connectivity in freezing of gait in Parkinson’s disease

Karthik Sreenivasan1, Ece Bayram1, Sarah J. Banks1, Xiaowei Zhuang1, Virendra Mishra1, Zhengshi Yang1, Christopher Bird1, Dietmar Cordes1, Irene Litvan2, Brent Bluett1

1Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA, 2University of California San Diego

Introduction: Executive dysfunction plays a role in Parkinson’s disease freezing of gait (PD-FOG). Neuroimaging studies have revealed PD-FOG is associated with impaired functional connectivity within the fronto-parietal network (FPN). PD-FOG often responds to levodopa, however the effects of levodopa on the FPN in PD-FOG have yet to be investigated.  

Methods: Preliminary analyses were performed using 9 PD-FOG, 10 PD without FOG (PD-nFOG) and 10 healthy controls (HCs). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). PD-FOG and PD-nFOG patients were scanned during the levodopa OFF and ON states. Preprocessed rs-fMRI from all groups were input to a spatial independent component analysis (ICA) and the left and right FPN consistent with previous reports was identified. Between group comparisons (HC vs PD groups (OFF and ON)), as well as OFF versus ON comparisons for both PD groups were performed.

Results: Altered connectivity in both PD groups was mitigated by levodopa in both the left and the right FPN. Connectivity differences in the left FPN for both PD groups were mainly seen in the parietal region, which were mitigated by levodopa. The right FPN showed altered connectivity in the frontal and parietal regions, which was somewhat normalized with levodopa in both PD groups. Although levodopa mitigated altered connectivity in both PD groups, it had a greater effect in PD-nFOG than PD-FOG.

Conclusions: Our findings suggest that altered functional connectivity within the FPN network improves somewhat in PD-FOG with levodopa, but not to the same degree as in PD-nFOG.