Deep Brain Stimulation Reduces Conflict-Related Theta and Error-Related Negativity in Patients With Obsessive-Compulsive Disorder.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with alterations of cortico-striato-thalamo-cortical loops and impaired performance monitoring. Electrophysiological markers such as conflict-related medial frontal theta (MFT) and error-related negativity (ERN) may be altered by clinically effective deep brain stimulation (DBS) of the anterior limb of the internal capsule and nucleus accumbens (ALIC/NAc). We hypothesized that ALIC/NAc DBS modulates electrophysiological performance monitoring markers. MATERIALS AND METHODS: Fifteen patients (six male) with otherwise treatment-refractory OCD receiving ALIC/NAc DBS performed a flanker task with EEG recordings at three sessions: presurgery and at follow-up with DBS on and off. We examined MFT, ERN, and task performance. Furthermore, we investigated interrelations with clinical efficacy and then explored the influence of the location of individual stimulation volumes on EEG modulations. RESULTS: MFT and ERN were significantly attenuated by DBS with differences most pronounced between presurgery and DBS-on states. Also, we observed reaction time slowing for erroneous responses during DBS-off. Larger presurgery ERN amplitudes were associated with decreased clinical efficacy. Exploratory anatomical analyses suggested that stimulation volumes encompassing the NAc were associated with MFT modulation, whereas ALIC stimulation was associated with modulation of the ERN and clinical efficacy. CONCLUSION: ALIC/NAc DBS diminished MFT and ERN, demonstrating modulation of the medial frontal performance monitoring system in OCD. Furthermore, our findings encourage further studies to explore the ERN as a potential predictor for clinical efficacy.

Internal Capsule/Nucleus Accumbens Deep Brain Stimulation Increases Impulsive Decision Making in Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation of the anterior limb of the internal capsule (ALIC)/nucleus accumbens is an effective treatment in patients with obsessive-compulsive disorder but may increase impulsive behavior. We aimed to investigate how active stimulation alters subdomains of impulsive decision making and whether respective effects depend on the location of stimulation sites. METHODS: We assessed 15 participants with obsessive-compulsive disorder performing the Cambridge Gambling Task during active and inactive ALIC/nucleus accumbens deep brain stimulation. Specifically, we determined stimulation-induced changes in risk adjustment and delay aversion. To characterize underlying neural pathways, we computed probabilistic stimulation maps and applied fiber filtering based on normative structural connectivity data to identify "hot" and "cold" spots/fibers related to changes in impulsive decision making. RESULTS: Active stimulation significantly reduced risk adjustment while increasing delay aversion, both implying increased impulsive decision making. Changes in risk adjustment were robustly associated with stimulation sites located in the central ALIC and fibers connecting the thalamus and subthalamic nucleus with the medial and lateral prefrontal cortex. Both hot spots and fibers for changes in risk adjustment were robust to leave-one-out cross-validation. Changes in delay aversion were similarly associated with central ALIC stimulation, but validation hereof was nonsignificant. CONCLUSIONS: Our findings provide experimental evidence that ALIC/nucleus accumbens stimulation increases impulsive decision making in obsessive-compulsive disorder. We show that changes in risk adjustment depend on the location of stimulation volumes and affected fiber bundles. The relationship between impulsive decision making and long-term clinical outcomes requires further investigation.

Performance monitoring in obsessive-compulsive disorder: Insights from internal capsule/nucleus accumbens deep brain stimulation.

BACKGROUND: Symptoms of obsessive-compulsive disorder (OCD) are partly related to impaired cognitive control processes and theta modulations constitute an important electrophysiological marker for cognitive control processes such as signaling negative performance feedback in a fronto-striatal network. Deep brain stimulation (DBS) targeting the anterior limb of the internal capsule (ALIC)/nucleus accumbens (NAc) shows clinical efficacy in OCD, while the exact influence on the performance monitoring system remains largely unknown. METHODS: Seventeen patients with treatment-refractory OCD performed a probabilistic reinforcement learning task. Analyses were focused on 4-8 Hz (theta) power, intertrial phase coherence (ITPC) and debiased weighted Phase-Lag Index (dwPLI) in response to negative performance feedback. Combined EEG and local field potential (LFP) recordings were obtained shortly after DBS electrode implantation to investigate fronto-striatal network modulations. To assess the impact of clinically effective DBS on negative performance feedback modulations, EEG recordings were obtained pre-surgery and at follow-up with DBS on and off. RESULTS: Medial frontal cortex ITPC, striatal ITPC and striato-frontal dwPLI were increased following negative performance feedback. Decreased right-lateralized dwPLI was associated with pre-surgery symptom severity. ITPC was globally decreased during DBS-off. CONCLUSION: We observed a theta phase coherence mediated fronto-striatal performance monitoring network. Within this network, decreased connectivity was related to increased OCD symptomatology, consistent with the idea of impaired cognitive control in OCD. While ALIC/NAc DBS decreased theta network activity globally, this effect was unrelated to clinical efficacy and performance monitoring.

Deep brain stimulation for Tourette syndrome.

Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, often associated with behavioral disorders, with typical onset in early childhood. In most patients, the symptoms decrease spontaneously when adulthood is reached, or can be treated with behavioral therapy or medication. Only a small proportion of patients are candidates for surgical treatment. In 1999, thalamic deep brain stimulation (DBS) was introduced for intractable Tourette syndrome. Since then, a diversity of targets have been used, located mainly at the level of the medial part of the thalamus, in the globus pallidus internus (anteromedial limbic and posteroventrolateral motor part), the globus pallidus externus, and the internal capsule/nucleus accumbens. The pathophysiology of Tourette syndrome is still a matter of considerable debate. Current knowledge of cortical-basal ganglia-thalamocortical circuits provides explanations for the beneficial effects of DBS on tics. Inclusion and exclusion criteria have been formulated to identify good candidates for DBS. Because of the small number of patients, there is a strong need for multicenter double-blind trials with standard protocols.