title: Similar circuits but different connectivity patterns between the cerebellum, basal ganglia, and supplementary motor area in early Parkinson's disease patients and controls during predictive motor timing.
abstract: OBJECTIVE
  The cerebellum, basal ganglia (BG), and other cortical regions, such as supplementary motor area (SMA) have emerged as important structures dealing with various aspects of timing, yet the modulation of functional connectivity between them during motor timing tasks remains unexplored.
  
  
  METHODS
  We used dynamic causal modeling to investigate the differences in effective connectivity (EC) between these regions and its modulation by behavioral outcome during a motor timing prediction task in a group of 16 patients with early Parkinson's disease (PD) and 17 healthy controls. Behavioral events (hits and errors) constituted the driving input connected to the cerebellum, and the modulation in connectivity was assessed relative to the hit condition (successful interception of target).
  
  
  RESULTS
  The driving input elicited response in the target area, while modulatory input changed the specific connection strength. The neuroimaging data revealed similar structure of intrinsic connectivity in both groups with unidirectional connections from cerebellum to both sides of the BG, from BG to the SMA, and then from SMA to the cerebellum. However, the type of intrinsic connection was different between two groups. In the PD group, the connection between the SMA and cerebellum was inhibitory in comparison to the HC group, where the connection was activated. Furthermore, the modulation of connectivity by the performance in the task was different between the two groups, with decreased connectivity between the cerebellum and left BG and SMA and a more pronounced symmetry of these connections in controls. In the same time, there was an increased EC between the cerebellum and both sides of BG with more pronounced asymmetry (stronger connection with left BG) in patients. In addition, in the PD group the modulatory input strengthened inhibitory connectivity between the SMA and the cerebellum, while in the HC group the excitatory connection was slightly strengthened.
  
  
  CONCLUSIONS
  Our findings indicate that although early PD subjects and controls use similar functional circuits to maintain a successful outcome in predictive motor timing behavior, the type and strength of EC and its modulation by behavioral performance differ between these two groups. These functional differences might represent the first step of cortical reorganization aimed at maintaining a normal performance in the brain affected by early Parkinson's disease and may have implications for the neuro-rehabilitation field.
authors.affiliation: Faculty of Medicine, First Department of Neurology, St. Anne's Teaching Hospital, Masaryk University, Brno, Czech Republic.
authors.forename: Ivica
authors.initials: I
authors.lastname: Husárová
authors.forename: Michal
authors.initials: M
authors.lastname: Mikl
authors.forename: Ovidiu V
authors.initials: OV
authors.lastname: Lungu
authors.forename: Radek
authors.initials: R
authors.lastname: Mareček
authors.forename: Jiří
authors.initials: J
authors.lastname: Vaníček
authors.forename: Martin
authors.initials: M
authors.lastname: Bareš
mesh_terms: D001288:Attention; D001479:Basal Ganglia / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D002531:Cerebellum / Q000503:physiopathology*; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D010300:Parkinson Disease; D011597:Psychomotor Performance; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: Basal ganglia; Parkinson's disease; cerebellum; connectivity; cortical reorganization; motor timing; prediction; supplementary motor area