title: Reduced task-related functional connectivity during a set-shifting task in unmedicated early-stage Parkinson's disease patients.
abstract: Patients with Parkinson's disease (PD) often suffer from cognitive impairments, including set-shifting deficits, in addition to the characteristic motor symptoms. It is hypothesized that the striatal dopamine depletion leads to a sub-optimal functional connectivity between task-related brain areas and consequently results in impaired task-performance. In this study, we aimed to examine this hypothesis by investigating the task-related functional connectivity of brain areas that are believed to be involved in set-shifting, such as the dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex (PPC) and the superior frontal gyrus (SFG), during a set-shifting task. We obtained functional imaging data from 18 early-stage PD patients and 35 healthy controls, matched at the group level, using a newly developed rule-based set-shifting task that required participants to manually respond to arrow stimuli based on their location on the screen of their direction.
  
  
  
  We found that early stage PD patients, compared with controls, showed (1) a decrease in positive coupling between the left DLPFC and the right insular cortex, and the right SFG and anterior cingulate cortex, (2) an increase in negative coupling between the right SFG and the anterior cingulate cortex, primary motor cortex, precuneus, and PPC, and (3) an increase in negative coupling between the left DLPFC and the left and right SFG. These results indicate that important task-related areas of PD patients have decreased functional connectivity with task-related regions and increased connectivity with task-unrelated areas.
  
  
  
  The disruption of functional connectivity in early stage PD patients during set-shifting reported here is likely compensated for by the local hyperactivation we reported earlier, thereby forestalling behavioural deficits.
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Corine C
authors.initials: CC
authors.lastname: de Bondt
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. njhmgerrits@gmail.com.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands. njhmgerrits@gmail.com.
authors.forename: Niels J H M
authors.initials: NJ
authors.lastname: Gerrits
authors.affiliation: Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Department of Neurology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Henk W
authors.initials: HW
authors.lastname: Berendse
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.|Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Ysbrand D
authors.initials: YD
authors.lastname: van der Werf
mesh_terms: D001288:Attention / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D056344:Executive Function / Q000502:physiology*; D030141:Feedback, Psychological / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D014796:Visual Perception / Q000502:physiology
keywords: Compensation; Functional magnetic resonance imaging; Parkinson’s disease; Set-shifting; Task-related functional connectivity