title: Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity.
abstract: OBJECTIVE
  Parkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully understood. In a combined longitudinal and cross-sectional study, we investigated how planning deficits progress over time in the early stages of PD compared to matched healthy controls. We used functional magnetic resonance imaging (fMRI) to identify accompanying neural dynamics.
  
  
  METHODS
  Seventeen PD patients and 20 healthy controls performed a parametric Tower of London task at two time points separated by ∼3 years (baseline and follow-up). We assessed task performance longitudinally in both groups; at follow-up, a subset of participants (14 patients, 19 controls) performed a parallel version of the task during fMRI. We performed meta-analyses to localize regions-of-interest (ROIs), that is, the bilateral dorsolateral prefrontal cortex (DLPFC), inferior parietal cortex, and caudate nucleus, and performed group-by-task analyses and within-group regression analyses of planning-related neural activation. We studied task-related functional connectivity of seeds in the DLPFC and caudate nucleus.
  
  
  RESULTS
  PD patients, compared with controls, showed impaired task performance at both time-points, while both groups showed similar performance reductions from baseline to follow-up. Compared to controls, patients showed lower planning-related brain activation together with decreased functional connectivity.
  
  
  CONCLUSIONS
  These findings support the notion that planning is affected early in the PD disease course, and that this impairment in planning is accompanied by decreases in both task-related brain activity and connectivity.
authors.affiliation: Department of Emotion & Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: James P
authors.initials: JP
authors.lastname: Trujillo
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Niels J H M
authors.initials: NJ
authors.lastname: Gerrits
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.|Department of Psychiatry, VUmc, Amsterdam, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Vriend
authors.affiliation: Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.|Department of Neurology, VUmc, 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), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.|Department of Psychiatry, VUmc, Amsterdam, The Netherlands.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
authors.affiliation: Department of Emotion & Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center (VUmc), Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, The Netherlands.
authors.forename: Ysbrand D
authors.initials: YD
authors.lastname: van der Werf
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D003430:Cross-Sectional Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology*; D011340:Problem Solving / Q000502:physiology*; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
keywords: cognitive load; executive function; frontoparietal; frontostriatal; functional connectivity