Deep Brain Stimulation For Obsessive-compulsive Disorder Research Articles

Therapeutic DBS for OCD Suppresses the Default Mode Network.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is an emerging treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Therapeutic DBS for OCD suppresses BOLD activity within a distributed set of regions within the DMN relative to non-therapeutic configurations. We propose that these effects may be mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.

A Reproducible Pipeline for Parcellation of the Anterior Limb of the Internal Capsule

BackgroundThe anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. MethodsFollowing algorithm development and refinement, we analyzed 43 control participants, each with 2 sets of 3T magnetic resonance imaging data and a subset of 5 control participants with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on PFC regions of interest, and we analyzed the relationships among bundles. ResultsWe successfully reproduced the topographies established by previous anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intraparticipant variability than interparticipant variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. ConclusionsOur diffusion magnetic resonance imaging algorithm reliably generates biologically validated ALIC white matter reconstructions, thereby allowing for more precise modeling of fibers for neuromodulation therapies.

Adolescent OCD Patient and Caregiver Perspectives on Identity, Authenticity, and Normalcy in Potential Deep Brain Stimulation Treatment.

The ongoing debate within neuroethics concerning the degree to which neuromodulation such as deep brain stimulation (DBS) changes the personality, identity, and agency (PIA) of patients has paid relatively little attention to the perspectives of prospective patients. Even less attention has been given to pediatric populations. To understand patients' views about identity changes due to DBS in obsessive-compulsive disorder (OCD), the authors conducted and analyzed semistructured interviews with adolescent patients with OCD and their parents/caregivers. Patients were asked about projected impacts to PIA generally due to DBS. All patient respondents and half of caregivers reported that DBS would impact patient self-identity in significant ways. For example, many patients expressed how DBS could positively impact identity by allowing them to explore their identities free from OCD. Others voiced concerns that DBS-related resolution of OCD might negatively impact patient agency and authenticity. Half of patients expressed that DBS may positively facilitate social access through relieving symptoms, while half indicated that DBS could increase social stigma. These views give insights into how to approach decision-making and informed consent if DBS for OCD becomes available for adolescents. They also offer insights into adolescent experiences of disability identity and "normalcy" in the context of OCD.

Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes.

Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).

Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder.

Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD. Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAc-ALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG. The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude. These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD. Clinical trial registration no.: NCT02398318 (ClinicalTrials.gov).

Clinical practice guidelines on the use of deep brain stimulation for the treatment of obsessive-compulsive disorder: systematic review.

Deep brain stimulation (DBS) has been proposed to improve symptoms of obsessive-compulsive disorder (OCD) but is not yet an established therapy. To identify relevant guidelines and assess their recommendations for the use of DBS in OCD. Medline, Embase, American Psychiatric Association PsycInfo and Scopus were searched, as were websites of relevant societies and guideline development organisations. The review was based on the PRISMA recommendations, and the search strategy was verified by a medical librarian. The protocol was developed and registered with PROSPERO (CRD42022353715). The guidelines were assessed for quality using the AGREE II instrument. Nine guidelines were identified. Three guidelines scored >80% on AGREE II. 'Scope and Purpose' and 'Editorial Independence' were the highest scoring domains, but 'Applicability' scores were low. Eight guidelines recommended that DBS is used after all other treatment options have failed to alleviate OCD symptoms. One guideline did not recommend DBS beyond a research setting. Only one guideline performed a cost-effectiveness analysis; the other eight did not provide details on safe or effective DBS protocols. Despite a very limited evidence base, eight of the nine identified guidelines supported the use of DBS for OCD as a last line of therapy; however, multiple aspects of DBS provision were not addressed.

The role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder

Despite extensive research efforts, the pathophysiology of obsessive-compulsive disorder (OCD) is still largely unknown. The dorsal anterior cingulate cortex (dACC) plays an important role in cognitive control and is therefore hypothesized to contribute to the pathogenesis of OCD. In this review, we aim to gain a wider understanding of the specific functions of the dACC and its role in the pathophysiology of OCD. The dACC is part of the cortico-basal ganglia-thalamo-cortical loop, where it forms connections between sensory input streams, cognitive and affective processing regions, and structures that regulate behaviour. This position facilitates a broad function for the dACC in multiple domains, which center on goal-directed behaviour and reward-based learning. When presented with a certain threatening stimulus, the dACC instructs downstream structures to select actions to respond to this particular stimulus, based on previous experiences We hypothesize that hyperactivity of the dACC may impair goal-directed behaviour in OCD patients which in turn may lead to obsessive-compulsive symptoms by creating an over-reliance on threatening stimuli and inadequate selection of neutralizing actions. The working mechanisms of cognitive behavioural therapy, serotonergic medication, repetitive transcranial magnetic stimulation and deep brain stimulation in OCD may be in part explained by the normalization of the activity of the dACC within the cortico-basal ganglia-thalamo-cortical (CBGTC) loop.

Patient feedback and psychosocial outcomes of deep brain stimulation in people with obsessive–compulsive disorder

Severe and refractory psychiatric patients can experience complex and profound changes in symptomology, functioning and well-being from deep brain stimulation (DBS) therapy. Currently, the efficacy of DBS is assessed by clinician rated scales of primary symptoms, yet this does not capture the multitude of DBS mediated changes or represent the patient perspective. We aimed to elucidate the patient perspective in psychiatric DBS application by investigating 1) symptomatic, and 2) psychosocial changes, 3) therapeutic expectations and satisfaction, 4) decision-making capacity, and 5) clinical care recommendations from treatment refractory obsessive–compulsive disorder (OCD) DBS patients. Participants enrolled in an open label clinical trial of DBS therapy for OCD who had reached clinical response were invited to participate in a follow up survey. Participants completed a 1) feedback survey relating to goals, expectations, and satisfaction of therapy, and 2) self-report questionnaires on psychosocial functioning including quality of life, cognitive insight, locus of control, rumination, cognitive flexibility, impulsivity, affect, and well-being. Greatest change was reported for quality of life, rumination, affect and cognitive flexibility. Participants reported realistic expectations, high satisfaction, adequate pre-operative education and decision-making capacity; and advocated for greater access to DBS care and more widespread support services. This is the first identified investigation on psychiatric patient perspectives of functioning and therapeutic outcomes following DBS. Insights from the study have implications for informing psychoeducation, clinical practices, and neuroethical debates. We encourage a greater patient-centred and biopsychosocial approach in evaluating and managing OCD DBS patients, by considering personally meaningful goals and addressing symptomatic and psychosocial recovery.

A comparison of how deep brain stimulation in two targets with anti-compulsive efficacy modulates brain activity using fMRI in awake rats.

Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS. Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accumbens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypothesized that stimulation at both targets would result in partially overlapping BOLD responses. Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and connections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.

Cognitive behavioral therapy in patients with deep brain stimulation for obsessive-compulsive disorder: a matched controlled study.

Deep brain stimulation (DBS) is effective for refractory obsessive-compulsive disorder (OCD). Post-operative cognitive behavioral therapy (CBT) may augment the effects of DBS, but previous results are conflicting. Here, we investigated whether CBT augments the effect of DBS for OCD. Patients with and without CBT following DBS of the ventral anterior limb of the internal capsule were included. First, we analyzed Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D) scores before, during and after CBT in all patients with CBT. Second, we matched patients with and without CBT based on clinical baseline variables and initial response to DBS and compared the course of Y-BOCS and HAM-D scores over the same timeframe. In total, 36 patients with and 16 patients without CBT were included. Average duration of CBT was 10.4 months (s.d. 6.4). In the 36 patients with CBT, Y-BOCS scores decreased on average by 3.8 points (14.8%) from start until end of CBT (p = 0.043). HAM-D scores did not decrease following CBT. Second, 10 patients with CBT were matched to 10 patients without CBT. In both groups, Y-BOCS scores decreased equally from start until end of CBT or over a similar timeframe (10% in CBT group v. 13.1% in no-CBT group, p = 0.741). Obsessive-compulsive symptoms decreased over time in patients with and without post-operative CBT. Therefore, further improvement may be attributed to late effects of DBS itself. The present study emphasizes the need for prospective randomized controlled studies, examining the effects of CBT.

Deep brain stimulation for refractory obsessive-compulsive disorder: A review and analysis of the FDA MAUDE database.

Background: Deep brain stimulation (DBS) is used as a treatment option for patients diagnosed with a form of obsessive-compulsive disorder (OCD) that is highly resistant to conventional treatment methods. In 2009, DBS was granted a humanitarian device exemption-approval by the Food and Drug Administration after promising preliminary data. Monitoring of long-term safety data through post market surveillance of adverse events has not yet been conducted for DBS in OCD patients. This study aims to address this critical knowledge gap.Methods: All patient- and device-related (PR; DR) reports from January 1, 2012, to December 31, 2021, were downloaded and compiled from the manufacturer and user facility device experience (MAUDE) database pertaining to DBS for OCD using the product class name “Deep Brain Stimulator For OCD.” Data in this study were examined using descriptive statistics to evaluate for frequency of reporting.Results: The most frequently reported PR adverse event categories included psychiatric (40%), neurological (19%), other (14%), decreased therapeutic response (10%), and infections (10%). The most frequent DR reports were high impedance (14%), energy output problem (7%), battery problem (7%), malposition of device (7%), and improper/incorrect procedure or method (7%).Conclusion: The PR and DR adverse events in our study align with the previous findings of adverse events. They also further solidify that DBS for refractory OCD may be a viable option for the right patient population. However, further studies are essential given the limitations of the MAUDE database.

ID:16509 Long-Term Ecological Assessment of Intracranial Electrophysiology Synchronized to Behavioral Markers in Obsessive-Compulsive Disorder

Despite the promise of deep brain stimulation (DBS) targeted to the ventral capsule/ventral striatum for treatment of severe obsessive-compulsive disorder (OCD), 25-40% of individuals do not respond to DBS treatment. This may be due to the current ‘open loop’ stimulation paradigm, where constant stimulation parameters do not address the dynamic nature of OCD symptoms. Adaptive deep brain stimulation (aDBS) has emerged as a potential strategy for improving efficacy of DBS for OCD. In an aDBS system, stimulation parameters are automatically adjusted based on detection of neural signatures related to symptoms or side effects of DBS.

Effectiveness and safety of deep brain stimulation for patients with refractory obsessive compulsive disorder and comorbid autism spectrum disorder; A case series

Background: Deep brain stimulation (DBS) is effective for patients with treatment refractory obsessive-compulsive disorder (OCD). Autism spectrum disorder (ASD) is present in up to a third of all patients with OCD, but it is unknown whether effectiveness of DBS for OCD also applies for patients with comorbid ASD. The present case series is the first to examine effectiveness on OCD symptoms and safety of DBS in patients with OCD and ASD specifically.Methods: Six consecutive patients with treatment-refractory OCD and comorbid ASD received DBS of the ventral anterior limb of the internal capsule (vALIC) or medial forebrain bundle (MFB). We examined effectiveness of DBS on symptoms of OCD and depression with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D), respectively. We included qualitative data to describe the course of treatment in individual patients with OCD and ASD.Results: We found that DBS significantly decreased symptoms of OCD (p < .001) and depression (p = .007). Four out of six patients with OCD and comorbid ASD were responders (decrease ≥ 35% in Y-BOCS), one patient was partial-responder (decrease 25–35% in Y-BOCS) and one patient did not respond (decrease ≤ 25% in Y-BOCS). Serious adverse events were an infection of the DBS system, and a suicide attempt.Conclusions: Though present results are preliminary, DBS reduced symptoms of OCD and depression in patients with OCD and comorbid ASD. Comorbid ASD should therefore not be seen as a contra-indication for DBS in OCD.

Why Has Deep Brain Stimulation Had So Little Impact in Psychiatry?

Over two decades ago, the first scientific publication on deep brain stimulation (DBS) in psychiatry was published. The evidence for effectiveness of DBS for several psychiatric disorders has been steadily accumulating since the first report of DBS for Obsessive Compulsive Disorder (OCD) in 1999. However, the number of psychiatric patients treated with DBS is lagging behind, particularly in comparison with neurology. The number of patients treated with DBS for psychiatric indications worldwide probably does not exceed 500, compared to almost 300,000 patients with neurological disorders that have been treated with DBS within the same period of 20 years. It is not the lack of patients, knowledge, technology, or efficacy of DBS that hinders its development and application in psychiatry. Here, we discuss the reasons for the gap between DBS in neurology and in psychiatry, which seemed to involve the scientific and social signature of psychiatry.

Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in obsessive-compulsive disorder.

Detection of neural signatures related to pathological behavioral states could enable adaptive deep brain stimulation (DBS), a potential strategy for improving efficacy of DBS for neurological and psychiatric disorders. This approach requires identifying neural biomarkers of relevant behavioral states, a task best performed in ecologically valid environments. Here, in human participants with obsessive-compulsive disorder (OCD) implanted with recording-capable DBS devices, we synchronized chronic ventral striatum local field potentials with relevant, disease-specific behaviors. We captured over 1,000 h of local field potentials in the clinic and at home during unstructured activity, as well as during DBS and exposure therapy. The wide range of symptom severity over which the data were captured allowed us to identify candidate neural biomarkers of OCD symptom intensity. This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders.

Pressing ethical issues in considering pediatric deep brain stimulation for obsessive-compulsive disorder

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.

Patient-specific connectomic models correlate with, but do not reliably predict, outcomes in deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. To address these gaps, we performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. With this best-practices approach, no model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Thus, patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

A-65 Quality Analysis of Deep Brain Stimulation for Obsessive–Compulsive Disorder Using a Neuropsychological Assessment Battery

Abstract Objective We completed a case study to investigate whether there are cognitive changes after Deep Brain Stimulation (DBS) surgery in the treatment of refractory Obsessive–Compulsive Disorder (OCD) as an initiation of a quality analysis due to increased referrals for this procedure at our institution. Method We evaluated a 21-year-old male before and after bilateral nucleus accumbens DBS placement for OCD. His pre-operative neurosurgery evaluation and brain imaging were unremarkable. Post-operative imaging revealed stable changes of bilateral DBS lead placement. Pre and post-operative neuropsychological testing included measures of mental status, language, memory, attention, and executive functioning. Results A reliable change estimate was obtained for each test. There was no significant change in performance on the Mini-Mental State Exam, Boston Naming Test, Logical Memory I/II, Faces I, Rey Complex Figure Test (RCFT) immediate and delayed recall, Wisconsin Card Sorting Test-64, Trail Making Tests A &amp; B, Letter Fluency, Animal Fluency, and Stroop Color and Word Test (Stroop) color and color-word condition. There was significant decline for all California Verbal Learning Test-Second Edition trials (trials 1–5, short delay recall, and long delay recall) and RCFT recognition. There was significant improvement for the Stroop word condition. Conclusions. Given mixed findings, it is unclear the extent to which DBS impacted this patient’s overall cognitive functioning. Meanwhile, he showed improvement in OCD symptoms, to the degree that he could live alone, maintain employment, and independently manage daily activities. There is need for future studies to examine the cognitive effects of DBS for OCD, with larger samples and a control group.

Four-six year clinical follow-up of deep brain stimulation for obsessive compulsive disorder

BackgroundOver the past 20 years a number of robust studies have established the clinical effectiveness and safety of Deep brain stimulation (DBS) in adults with profound multi-treatment-refractory obsessive-compulsive disorder (OCD). However long term (&gt;12 months) outcomes with this novel neurosurgical intervention are still inadequately reported. Our group conducted the first UK study of DBS in OCD between 2013-2017. All participants in our trial achieved a responder status at 15 month endpoint and the main results were reported in 2019. A specialist multidisciplinary clinic was established after the trial to provide life-long aftercare in the form of scheduled clinical and hardware reviews. Here we are reporting a preliminary analysis of the long-term clinical, functional and social outcomes from this cohort.MethodLong term follow-up clinical data (15–75 months, 2015 onwards) were prospectively collected from the participants who were enrolled in the original MRC-UCL pilot study of DBS for OCD. DBS parameters, battery health and status, social circumstances, mental state and medication adjustments were noted alongside the outcome measures of YBOCS at clinical follow-up encounters. Additional ratings of GAF, SDS and certain qualitative measures were recorded at least once every year since initial study completion.ResultFive out of six participants continued with DBS treatment and kept responder status. One participant had his DBS switched off and hardware removed. One participant had multiple hospital admissions to manage comorbidity progression to primary condition. One participant had OCD severity scores revised upwards despite continuing gains in QoL. Secondary outcomes generally matched the 15 month end point of initial trial. All participants experienced minor to major changes in their relationships with partners or family. Qualitative feedback indicated that DBS was well tolerated by 5/6 subjects but the burden of specialist follow-up remained significant.ConclusionOur long term follow-up data indicate that DBS is safe and conferred a sustained long-term benefit in reduction of obsessive-compulsive symptoms. A non-trivial burden of checking and maintenance of implanted hardware, comorbidity-unmasking following successful OCD treatment, perceived ‘burden of normality’ by the participant, need for life-long follow-ups with specialist multidisciplinary team including DBS nurses, highly specialist psychiatrists from National OCD service, neuropsychiatrists, neurologists and neurosurgeons partially counterbalances the gains offered by this treatment. Overall DBS offers a safe, effective and enduring alternative to participants who do not respond to any other form of OCD treatment and do not wish to undergo ablation surgery.

Double blind randomized controlled trial of deep brain stimulation for obsessive-compulsive disorder: Clinical trial design

Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1–2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.