title: Cognitive flexibility depends on white matter microstructure of the basal ganglia.
abstract: Ample evidence shows that the basal ganglia play an important role in cognitive flexibility. However, traditionally, cognitive processes have most commonly been associated with the prefrontal cortex. Indeed, current theoretical models of basal ganglia function suggest the basal ganglia interact with the prefrontal cortex and thalamus, via anatomical fronto-striato-thalamic circuits, to implement cognitive flexibility. Here we aimed to assess this hypothesis in humans by associating individual differences in cognitive flexibility with white matter microstructure of the basal ganglia. To this end we employed an attention switching paradigm in adults with ADHD and controls, leading to a broad range in task performance. Attention switching performance could be predicted based on individual differences in white matter microstructure in/around the basal ganglia. Crucially, local white matter showing this association projected to regions in the prefrontal cortex and thalamus. Our findings highlight the crucial role of the basal ganglia and the fronto-striato-thalamic circuit for cognitive flexibility.
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, PO Box 9104, 6500 HE Nijmegen, The Netherlands; Department of Neurology, University of California, San Francisco, CA 94158, USA. Electronic address: martine.vanschouwenburg@ucsf.edu.
authors.forename: M R
authors.initials: MR
authors.lastname: van Schouwenburg
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: A M H
authors.initials: AM
authors.lastname: Onnink
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, PO Box 9104, 6500 HE Nijmegen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: ter Huurne
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Kan
authors.affiliation: Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, PO Box 9104, 6500 HE Nijmegen, The Netherlands; Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, PO Box 9104, 6500 HE Nijmegen, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Max Planck Institute for Psycholinguistics, Department of Language and Genetics, PO Box 310, 6500 AH Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hoogman
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, PO Box 9104, 6500 HE Nijmegen, The Netherlands.
authors.forename: J K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, PO Box 9104, 6500 HE Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Cools
mesh_terms: D000223:Adaptation, Psychological; D000328:Adult; D016880:Anisotropy; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D001479:Basal Ganglia / Q000473:pathology*; D001921:Brain / Q000473:pathology; D003071:Cognition; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology; D009483:Neuropsychological Tests; D013647:Task Performance and Analysis
keywords: ADHD; Basal ganglia; Cognitive control; DTI; Fronto-striatal circuits; Structural connectivity