Differences in Connectivity among the Basal Ganglia, Cerebellum, and Supplementary Motor Area in Parkinson's Disease and Healthy Controls during Predictive Motor Timing (IN6-1.006)

Abstract

Objective: The cerebellum, basal ganglia (BG), and other cortical regions have emerged as important structures for timing, yet the modulation of functional connectivity between them remains unexplored. Background Patients with Parkinson9s disease (PD) have marked deficits in motor and perceptual timing. We investigated the effective connectivity between the SMA, striatum, and cerebellum and its modulation during the motor timing task in healthy individuals and in early PD patients. Design/Methods: We used dynamic causal modeling on fMRI data obtained during a dynamic motor timing prediction task in 16 patients with PD and 17 healthy controls. Two types of behavioral events (hits and errors) constituted the driving input connected to the cerebellum, and the modulation was assessed relative to the hit condition. Results: The structure of intrinsic connectivity in both groups showed that the cerebellum has unidirectional connections with both sides of the BG, the BG with the SMA, and the SMA with the cerebellum. In the control group, the modulatory input decreased the relation of the cerebellum with the SMA and left BG with a more pronounced symmetry of these connections. PD subjects showed an increased EC between the cerebellum and both BG sides with more pronounced asymmetry (stronger connection with left BG). The modulatory input decreased the relation of the SMA with the cerebellum more in the PD subjects than in the controls. Conclusions: Although PD subjects and controls use similar functional circuits to maintain a successful outcome in predictive motor timing behavior, the strength of EC and its modulation differ. These functional changes represent the first step of cortical reorganization aimed at maintaining a normal performance in the brain affected by PD and implications for the neuro-rehabilitation field. Supported by: CEITEC - Central European Institute of Technology project (CZ.1.05/1.1.00/02.0068) from the European Regional Development Fund and by the Czech Ministry of Education Research Program MSM 0021622404. Disclosure: Dr. Bares has received personal compensation for activities with Novartis, Ipsen, Medtronic, Inc., UCB Pharma, GlaxoSmithKline, Inc., Neomed, Abbott Labratories as a consultant and a speaker. Dr. Husarova has received personal compensation for activities with Bayer Pharmaceutical Corporation and Neomed as a consultant. Dr. Mikl has nothing to disclose. Dr. Lungu has nothing to disclose. Dr. Marecek has nothing to disclose. Dr. Vanicek has nothing to disclose.