title: Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder.
abstract: Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kohl
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.|Faculty of Economics, Otto-von-Guericke-University, Magdeburg, Germany.|Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: T O J
authors.initials: TO
authors.lastname: Gruendler
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Huys
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Sildatke
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: T A
authors.initials: TA
authors.lastname: Dembek
authors.affiliation: Institute of Medical Statistics, Informatics, and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Vorderwulbecke
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Timmermann
authors.affiliation: Department of Psychiatry, Center for Neuroscience Program, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Ahmari
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Klosterkoetter
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Jessen
authors.affiliation: Department of Neurosurgery, University of Würzburg, Würzburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Sturm
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Visser-Vandewalle
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Cologne, University of Cologne, Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kuhn
mesh_terms: D000328:Adult; D046690:Deep Brain Stimulation; D005260:Female; D006801:Humans; D008297:Male; D009714:Nucleus Accumbens / Q000503:physiopathology*; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology* / Q000628:therapy*; D065808:Prepulse Inhibition / Q000502:physiology*; D016896:Treatment Outcome