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.
Highlights
The physiopathology of obsessive-compulsive disorder (OCD) is related to dysfunctions of cortical–subcortical loops,[1,2,3] including the ventral cognitive circuit partly composed of the anterolateral orbitofrontal cortex involved in motor and response inhibition.[3,4] for this study, the subthalamic nucleus (STN), an interesting target for deep brain stimulation (DBS) therapy in OCD,[5,6] was shown to be a key node of the cortico-striatothalamic-cortical loop of motor inhibition.[7]
The change in Yale-Brown Obsessive Compulsive Scale (YBOCS) introduced by the change in STN-DBS was close to significance with similar effect between the obsession and compulsion subscales
We found no significant difference on these behavioral measurements between the different OCD types
Summary
The physiopathology of obsessive-compulsive disorder (OCD) is related to dysfunctions of cortical–subcortical loops,[1,2,3] including the ventral cognitive circuit partly composed of the anterolateral orbitofrontal cortex involved in motor and response inhibition.[3,4] for this study, the subthalamic nucleus (STN), an interesting target for deep brain stimulation (DBS) therapy in OCD,[5,6] was shown to be a key node of the cortico-striatothalamic-cortical loop of motor inhibition.[7] It receives direct afferences from prefrontal regions[8] involved in executive functions, such as set-shifting[9] and decision-making,[10] that are impaired in OCD. Because the STN is supposed to act as a brake in high-conflict context by delaying the thalamic outputs onto motor areas before taking the right decision, this brake could be perturbed under STN-DBS, leading to more impulsive reactions, premature responses and/or shorter reaction times.[22,23,24]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
