title: Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.
abstract: Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA. evamoe@stanford.edu.|Neuroscience Program, SRI International, Menlo Park, CA, 94025, USA. evamoe@stanford.edu.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Müller-Oehring
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA.
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA.|Neuroscience Program, SRI International, Menlo Park, CA, 94025, USA.
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.affiliation: Valley Parkinson Clinic, Los Gatos, CA, 95032, USA.
authors.forename: Neng C
authors.initials: NC
authors.lastname: Huang
authors.affiliation: Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Poston
authors.affiliation: Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bronte-Stewart
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, 94025, USA.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schulte
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001288:Attention / Q000502:physiology; D001479:Basal Ganglia / Q000503:physiopathology*; D001931:Brain Mapping; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D012146:Rest / Q000502:physiology*; D012720:Severity of Illness Index; D057190:Stroop Test
chemical_list: D000978:Antiparkinson Agents
keywords: Cognitive control; Neural compensation; Parkinson’s disease; Response switching; Task-related and resting-state functional connectivity; fMRI