title: Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.
abstract: Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson's disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, United Kingdom.|Centre for BrainHealth, Univesity of Texas at Dallas, 2200 West Mockingbird Lane, Dallas, TX 75235, USA.
authors.forename: Vincenzo G
authors.initials: VG
authors.lastname: Fiore
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rigoli
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, United Kingdom.|Department of Neurology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Max-Philipp
authors.initials: MP
authors.lastname: Stenner
authors.affiliation: Department of Neurology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Zaehle
authors.affiliation: King's College London, Institute of Psychiatry, Psychology &Neuroscience, Department of Basic &Clinical Neuroscience, London, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Hirth
authors.affiliation: Department of Neurology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.|Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, United Kingdom.|Max Planck UCL Centre for Computational Psychiatry and Ageing Research, 10-12 Russell Square, London, WC1B 5EH, United Kingdom.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dolan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000503:physiopathology*; D046690:Deep Brain Stimulation / Q000379:methods*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009043:Motor Activity; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy*; D055815:Young Adult
chemical_list: D004298:Dopamine