title: Brain networks modulated by subthalamic nucleus deep brain stimulation.
abstract: Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour.
authors.affiliation: 1 Department of Neurology, Charité University Medicine Berlin, Campus Virchow, 13353 Berlin, Germany 2 Neurology Unit, Medicine Department, HFR Cantonal Hospital and Faculty of Sciences, University of Fribourg, 1708 Fribourg, Switzerland ettoreaccolla@gmail.com.
authors.forename: Ettore A
authors.initials: EA
authors.lastname: Accolla
authors.affiliation: 1 Department of Neurology, Charité University Medicine Berlin, Campus Virchow, 13353 Berlin, Germany 3 Department of Psychology, Goldsmiths, University of London, London SE14 6NW, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Herrojo Ruiz
authors.affiliation: 1 Department of Neurology, Charité University Medicine Berlin, Campus Virchow, 13353 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Horn
authors.affiliation: 4 Department of Neurosurgery, Charité University Medicine Berlin, Campus Virchow, 13353 Berlin, Germany.
authors.forename: Gerd-Helge
authors.initials: GH
authors.lastname: Schneider
authors.affiliation: 1 Department of Neurology, Charité University Medicine Berlin, Campus Virchow, 13353 Berlin, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schmitz-Hübsch
authors.affiliation: 5 LREN - Département des neurosciences cliniques, CHUV, Université de Lausanne, 1011 Lausanne, Switzerland 6 Max Planck Institute for Human Cognitive and Brain Science, 04103 Leipzig, Germany.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Draganski
authors.affiliation: 1 Department of Neurology, Charité University Medicine Berlin, Campus Virchow, 13353 Berlin, Germany 7 Berlin School of Mind and Brain, Humboldt University, 10117 Berlin, Germany 8 NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany 9 DZNE, Berlin, Germany.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Kühn
mesh_terms: D000368:Aged; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology; D001611:Beta Rhythm / Q000502:physiology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D046690:Deep Brain Stimulation; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004569:Electroencephalography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy; D020531:Subthalamic Nucleus / Q000000981:diagnostic imaging / Q000503:physiopathology
keywords: Parkinson’s disease; Parkinson’s disease: imaging; beta oscillations; deep brain stimulation; subthalamic nucleus