title: Compensatory fronto-parietal hyperactivation during set-shifting in unmedicated patients with Parkinson's disease.
abstract: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as mental rigidity, which can be measured as impaired set-shifting. Previous studies have shown that set-shifting deficits in patients with PD result from hypo-excitation of the caudate nucleus and lateral prefrontal cortices. The results of these studies may have been influenced by the inclusion of patients on dopaminergic medication, and by choosing set-shifting paradigms in which performance also depends on other cognitive mechanisms, such as matching-to-sample. To circumvent these potential confounding factors, we tested patients with PD that were not on dopamine replacement therapy, and we developed a new feedback-based paradigm to measure the cognitive construct set-shifting more accurately. In this case-control study, 18 patients with PD and 35 well-matched healthy controls performed the set-shifting task, while task-related neural activation was recorded using functional magnetic resonance imaging. Behaviourally, PD patients, compared with healthy controls, made more errors during repeat trials, but not set-shift trials. The patients, compared with controls, showed increased task-related activation of the bilateral inferior parietal cortex, and the right superior frontal gyrus, and decreased activation of the right ventrolateral prefrontal cortex during set-shift trials. Our findings suggest that, despite decreased task-related activation of the right ventrolateral prefrontal cortex, these early-stage unmedicated patients with PD do not yet suffer from set-shifting deficits due to compensatory hyperactivation in the inferior parietal cortex and the superior frontal gyrus.
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands. Electronic address: njhmgerrits@gmail.com.
authors.forename: Niels J H M
authors.initials: NJ
authors.lastname: Gerrits
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center (VUmc), 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
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Kim M W
authors.initials: KM
authors.lastname: Verhoef
authors.affiliation: Department of Psychiatry, 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 Anatomy & Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Groenewegen
authors.affiliation: Department of Neurology, 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 & Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Department of Psychiatry, VUmc, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
mesh_terms: D000328:Adult; D000368:Aged; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology*
keywords: Cognition; Compensation; Functional MRI; Parkinson's disease; Set-shifting