Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder: Progress and Opportunities.
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SUBMITTER: Goodman WK
PROVIDER: S-EPMC7239379 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder: Progress and Opportunities.
Goodman Wayne K WK Storch Eric A EA Cohn Jeffrey F JF Sheth Sameer A SA
The American journal of psychiatry 20200301 3
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Project description:BackgroundPrior promising results have been reported with deep brain stimulation (DBS) of the anterior limb of the internal capsule in cases with severe obsessive compulsive disorder (OCD) who had exhausted conventional therapies.MethodsIn this pilot study, six adult patients (2 male; 4 female) meeting stringent criteria for severe (minimum Yale-Brown Obsessive Compulsive Scale [Y-BOCS] of 28) and treatment-refractory OCD had DBS electrode arrays placed bilaterally in an area spanning the ventral anterior limb of the internal capsule and adjacent ventral striatum referred to as the ventral capsule/ventral striatum. Using a randomized, staggered-onset design, patients were stimulated at either 30 or 60 days following surgery under blinded conditions.ResultsAfter 12 months of stimulation, four (66.7%) of six patients met a stringent criterion as "responders" (> or =35% improvement in the Y-BOCS and end point Y-BOCS severity < or =16). Patients did not improve during sham stimulation. Depressive symptoms improved significantly in the group as a whole; global functioning improved in the four responders. Adverse events associated with chronic DBS were generally mild and modifiable with setting changes. Stimulation interruption led to rapid but reversible induction of depressive symptoms in two cases.ConclusionsThis pilot study suggests that DBS of the ventral capsule/ventral striatum region is a promising therapy of last resort for carefully selected cases of severe and intractable OCD. Future research should attend to subject selection, lead location, DBS programming, and mechanisms underpinning therapeutic benefits.
| S-EPMC5796545 | biostudies-literature
Project description:Objective: The present study aims to understand perceptions of deep brain stimulation (DBS) for severe obsessive-compulsive disorder (OCD) in adolescents among two groups: parents of children with a history of OCD and adults with a history of OCD. Methods: Two hundred sixty participants completed a questionnaire exploring their treatment history, relevant symptom severity, DBS knowledge, and DBS attitudes using an acceptability scale and a series of statements indicating levels of willingness or reluctance to consider DBS for adolescents with severe OCD or severe epilepsy. Results: Overall, participants found DBS to be fairly acceptable for adolescents with severe OCD, with 63% reporting at least 7/10 on a 0-10 acceptability Likert scale. Respondents were more willing to consider DBS for epilepsy than for OCD. Several factors were associated with greater willingness to consider DBS for OCD, including familiarity with DBS, the presence of suicidal thoughts, assurances of daily functioning improvements, and assurances of substantial symptom reduction. Concerns about safety, personality changes, and long-term effects on the body were associated with greatest reluctance to consider DBS for OCD. Conclusions: Our findings support the importance of increasing parents' familiarity with DBS, monitoring factors participants identified as most important to their DBS perceptions in future DBS research, and communicating benefits and risks clearly. We also highlight the need for further research on perceptions of DBS for severe and refractory OCD in adolescents.
| S-EPMC7984933 | biostudies-literature
Project description:Deep brain stimulation (DBS) is a neuro-psychosurgical technique widely accepted in movement disorders, such as Parkinson's disease. Since 1999, DBS has been explored for severe, chronic and treatment-refractory psychiatric diseases. Our review focuses on DBS in obsessive-compulsive disorder (OCD), considered as a last treatment resort by most of learned societies in psychiatry. Two main stimulation areas have been studied: the striatal region and the subthalamic nucleus. But, most of the trials are open-labeled, and the rare controlled ones have failed to highlight the most efficient target. The recent perspectives are otherwise encouraging. Indeed, clinicians are currently considering other promising targets. A case series of 2 patients reported a decrease in OCD symptoms after DBS in the medial forebrain bundle and an open-label study is exploring bilateral habenula stimulation. New response criteria are also investigating such as quality of life, or subjective and lived-experience. Moreover, first papers about cost-effectiveness which is an important criterion in decision making, have been published. The effectiveness of tractography-assisted DBS or micro-assisted DBS is studying with the aim to improve targeting precision. In addition, a trial involving rechargeable pacemakers is undergoing because this mechanism could be efficient and have a positive impact on cost-effectiveness. A recent trial has discussed the possibility of using combined cognitive behavioral therapy (CBT) and DBS as an augmentation strategy. Finally, based on RDoc Research, the latest hypotheses about the understanding of cortico-striato-thalamo-cortical circuits could offer new directions including clinical predictors and biomarkers to perform adaptive closed-loop systems in the next future.
| S-EPMC6526924 | biostudies-literature
Project description:Multiple surgical targets for treating obsessive-compulsive disorder with deep brain stimulation (DBS) have been proposed. However, different targets may modulate the same neural network responsible for clinical improvement. We analyzed data from four cohorts of patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens or the subthalamic nucleus (STN). The same fiber bundle was associated with optimal clinical response in cohorts targeting either structure. This bundle connected frontal regions to the STN. When informing the tract target based on the first cohort, clinical improvements in the second could be significantly predicted, and vice versa. To further confirm results, clinical improvements in eight patients from a third center and six patients from a fourth center were significantly predicted based on their stimulation overlap with this tract. Our results show that connectivity-derived models may inform clinical improvements across DBS targets, surgeons and centers. The identified tract target is openly available in atlas form.
| S-EPMC7335093 | biostudies-literature
Project description:Deep brain stimulation is a promising therapeutic approach for patients with treatment-resistant obsessive-compulsive disorder, a condition linked to abnormalities in corticobasal ganglia networks. Effective targets are placed in one of four subcortical areas with the goal of capturing prefrontal, anterior cingulate, and basal ganglia connections linked to the limbic system. These include the anterior limb of the internal capsule, the ventral striatum, the subthalamic nucleus, and a midbrain target. The goal of this review is to examine these 4 targets with respect to the similarities and differences of their connections. Following a review of the connections for each target based on anatomic studies in nonhuman primates, we examine the accuracy of diffusion magnetic resonance imaging tractography to replicate those connections in nonhuman primates, before evaluating the connections in the human brain based on diffusion magnetic resonance imaging tractography. Results demonstrate that the four targets generally involve similar connections, all of which are part of the internal capsule. Nonetheless, some connections are unique to each site. Delineating the similarities and differences across targets is a critical step for evaluating and comparing the effectiveness of each and how circuits contribute to the therapeutic outcome. It also underscores the importance that the terminology used for each target accurately reflects its position and its anatomic connections, so as to enable comparisons across clinical studies and for basic scientists to probe mechanisms underlying deep brain stimulation.
| S-EPMC9569132 | biostudies-literature
Project description:BackgroundRefractory obsessive-compulsive disorder (OCD) among adults is the first psychiatric indication of deep brain stimulation (DBS) to receive an FDA Humanitarian Device Exemption (HDE). Given the HDE approval and encouraging evidence that has since emerged, exploration of DBS for OCD may expand to adolescents in the future. More than 100,000 adolescents in the U.S. suffer from refractory OCD, and there is already a precedent for the transition of DBS in adults to children in the case of dystonia. However, the risk-benefit analysis of pediatric DBS for OCD may be more complex and raise different ethical questions compared to pediatric DBS for dystonia.ObjectiveThis study aimed to gain insight into pressing ethical issues related to using DBS in adolescents with OCD.MethodsSemi-structured interviews were conducted with clinicians (n = 25) caring for pediatric patients with refractory OCD. Interview transcripts were coded with MAXQDA 2018 software and analyzed using thematic content analysis to identify emergent themes.ResultsFive central themes were identified in clinician responses, three of which were exacerbated in the pediatric DBS setting. Clinicians expressed concerns related to conditions of decision-making including adolescents' capacity to assent (80%), the lack of evidence about the outcomes and potential unknown effects of using DBS in adolescents with OCD (68%), and the importance of exhausting other treatment options before considering DBS (20%).ConclusionsStrategies to address clinician concerns include implementation of validated decision support tools and further research into the outcomes of pediatric DBS for OCD to establish clear guidelines for patient selection.
| S-EPMC8608753 | biostudies-literature
Project description:BackgroundIn spite of advances in psychotherapy and pharmacotherapy, there are still a significant number of patients with depression and obsessive-compulsive disorder that are not aided by either intervention. Although still in the experimental stage, deep brain stimulation (DBS) offers many advantages over other physically-invasive procedures as a treatment for these psychiatric disorders. The purpose of this study is to systematically review reports on clinical trials of DBS for obsessive-compulsive disorder (OCD) and treatment-resistant depression (TRD). Locations for stimulation, success rates and effects of the stimulation on brain metabolism are noted when available. The first observation of the effects of DBS on OCD and TRD came in the course of using DBS to treat movement disorders. Reports of changes in OCD and depression during such studies are reviewed with particular attention to electrode locations and associated adverse events; although these reports were adventitious observations rather than planned. Subsequent studies have been guided by more precise theories of structures involved in DBS and OICD. This study suggests stimulation sites and prognostic indicators for DBS. We also briefly review tractography, a relatively new procedure that holds great promise for the further development of DBS.MethodsArticles were retrieved from MEDLINE via PubMed. Relevant references in retrieved articles were followed up. We included all articles reporting on studies of patients selected for having OCD or TRD. Adequacy of the selected studies was evaluated by the Jadad scale. Evaluation criteria included: number of patients, use of recognized psychiatric rating scales, and use of brain blood flow measurements. Success rates classified as "improved" or "recovered" were recorded. Studies of DBS for movement disorders were included if they reported coincidental relief of depression or reduction in OCD. Most of the studies involved small numbers of subjects so individual studies were reviewed.ResultsWhile the number of cases was small, these were extremely treatment-resistant patients. While not everyone responded, about half the patients did show dramatic improvement. Associated adverse events were generally trivial in younger psychiatric patients but often severe in older movement disorder patients. The procedures differed from study to study, and the numbers of patients was usually too small to do meaningful statistics or make valid inferences as to who will respond to treatment.ConclusionsDBS is considered a promising technique for OCD and TRD. Outstanding questions about patient selection and electrode placement can probably be resolved by (a) larger studies, (b) genetic studies and (c) imaging studies (MRI, fMRI, PET, and tractography).
| S-EPMC2838907 | biostudies-literature
Project description:Recent approaches have suggested that deep brain stimulation (DBS) for obsessive-compulsive disorder relies on distributed networks rather than local brain modulation. However, there is insufficient data on how DBS affects brain metabolism both locally and globally. We enrolled three patients with treatment-refractory obsessive-compulsive disorder with ongoing DBS of the bilateral ventral capsule/ventral striatum. Patients underwent resting-state 18F-fluorodeoxyglucose and positron emission tomography in both stimulation ON and OFF conditions. All subjects showed relative hypometabolism in prefronto-basal ganglia-thalamic networks compared to a healthy control cohort when stimulation was switched OFF. Switching the stimulation ON resulted in differential changes in brain metabolism. Locally, volumes of activated tissue at stimulation sites (n = 6) showed a significant increase in metabolism during DBS ON compared to DBS OFF (Mean difference 4.5 % ± SD 2.8; p = 0.012). Globally, differential changes were observed across patients encompassing prefrontal increase in metabolism in ON vs. OFF condition. Bearing in mind limitations of the small sample size, we conclude that DBS of the ventral capsule/ventral striatum for obsessive-compulsive disorder increases brain metabolism locally. Across distributed global networks, DBS appears to exert differential effects, possibly depending on localization of stimulation sites and response to the intervention.
| S-EPMC6770477 | biostudies-literature
Project description:OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.
| S-EPMC9884519 | biostudies-literature
Project description:BackgroundSymptoms 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.MethodsSeventeen 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.ResultsMedial 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.ConclusionWe 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.
| S-EPMC8261082 | biostudies-literature