title: Modulation of motor inhibition by subthalamic stimulation in obsessive-compulsive disorder.
abstract: High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical-cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task. First, we found that patients were faster to respond and had slower motor inhibition processes when stimulated. Second, the subthalamic stimulation modulated the amplitude and delayed inhibition-related electroencephalographic responses. The power of reconstructed cortical current densities decreased in the stimulation condition in a parietal-frontal network including cortical regions of the inhibition network such as the superior parts of the inferior frontal gyri and the dorsolateral prefrontal cortex. Finally, dynamic causal modeling revealed that the subthalamic stimulation was more likely to modulate efferent connections from the basal ganglia, modeled as a hidden source, to the cortex. The connection from the basal ganglia to the right inferior frontal gyrus was significantly decreased by subthalamic stimulation. Beyond motor inhibition, our study thus strongly suggests that the mechanisms of action of high-frequency subthalamic stimulation are not restricted to the subthalamic nucleus, but also involve the modulation of distributed subcortical-cortical networks.
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: A
authors.initials: A
authors.lastname: Kibleur
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: G
authors.initials: G
authors.lastname: Gras-Combe
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: D
authors.initials: D
authors.lastname: Benis
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: J
authors.initials: J
authors.lastname: Bastin
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.|Clinique Universitaire de Psychiatrie, Pôle Psychiatrie Neurologie, Centre Hospitalier Universitaire, Grenoble, France.
authors.forename: T
authors.initials: T
authors.lastname: Bougerol
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.|Clinique Universitaire de Neurochirurgie, Pôle Tête et Cou, Centre Hospitalier Universitaire, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Chabardès
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.|Clinique Universitaire de Psychiatrie, Pôle Psychiatrie Neurologie, Centre Hospitalier Universitaire, Grenoble, France.
authors.forename: M
authors.initials: M
authors.lastname: Polosan
authors.affiliation: Université Grenoble Alpes, Grenoble, France.|Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: O
authors.initials: O
authors.lastname: David
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D046690:Deep Brain Stimulation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000503:physiopathology; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology* / Q000628:therapy*; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D020531:Subthalamic Nucleus / Q000503:physiopathology*