Objective: To evaluate how functional connectivity estimated by resting-state functional magnetic resonance imaging (rs-fMRI) is influenced by levodopa and associated with clinical symptoms in Parkinson’s disease (PD).

Background: PD patients suffer from various motor and non-motor symptoms, which are supposedly caused by dysfunction of cortical-basal ganglia network. Recent studies report altered functional brain connectivity in various neurodegenerative diseases, including PD. However, it remains unclear how functional connectivity changes in response to dopaminergic treatment and how it correlates with clinical symptoms.

Methods: 27 PD patients and 20 healthy control (HC) subjects participated in the study. PD patients were examined with standard cognitive batteries including MMSE, Frontal Assessment Battery (FAB), Raven Colored Progressive Matrices, and Rey-Osterrieth Complex Figure Test. Each subject was scanned twice for rs-fMRI on and off levodopa treatment on separate days. PD patients were recruited in a prospective open-label study. Age-matched healthy volunteers were studied by randomized double-blind placebo-control for levodopa. Rs-fMRI was obtained by 3T Siemens MRI. SPM12 was used to perform initial preprocessing steps. Functional connectivity was examined by ROI-based correlation approach.

Results: PD patients scored significantly less in FAB, RCPM, and ROCF as compared with HC. Functional connectivity increased 18.5% after levodopa administration in HC group. By contrast in PD group, levodopa induced only limited change (+9.8%) in overall connectivity. Motor disability of PD patients was hardly predicted by functional connectivity measured off medication, but was associated with cortico-basal ganglia connectivity measured after levodopa administration. Among the cognitive tests examined, FAB score was most closely associated with functional connectivity, particularly with those involving the frontal region.

Conclusions: Our data suggest that levodopa enhances functional brain connectivity in healthy subjects, but the capacity is compromised in PD patients. Such network insufficiency in PD might disturb information processing and cause cognitive impairment that does not respond to dopaminergic treatment.

Preliminary version of the study was presented at Annual Meeting of Japanese Society of Clinical Neurophysiology 2014 Fukuoka and Human Brain Mapping 2015 Hawaii.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/influence-of-levodopa-on-functional-brain-connectivity-in-parkinsons-disease/