Increased apathy post-interstitial laser capsulotomy for refractory obsessive-compulsive disorder.

BACKGROUND: MRI guided laser interstitial thermal therapy (M-LITT) capsulotomy has proven to be efficacious in decreasing refractory obsessive-compulsive disorder (OCD) related symptomatology yet capsulotomy either via radiosurgery or radiofrequency ablation has in some patients led to increased apathy following surgery. The current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via M-LITT for OCD. METHODS: Ten consecutive patients pre- and post-M-LITT completed measures of OCD, apathy, disinhibition, executive dysfunction, and depression (Mtime between = 1.3 years; 0.42-3.7 years). Reliable Change Index (RCI) was used to evaluate change in pre- and post-M-LITT. OCD symptom response was evaluated using percent change (Y-BOCS scores: 24-34 % reduction indicating partial response; ≥35% reduction indicating full response). RESULTS: Positive post-surgical change was noted in OCD symptomatology with >65% reporting a partial or full response. However, six patients endorsed increased apathy with half of the non-responders (e.g., less than <24% score reduction on Y-BOCS) reporting increases in apathy. Patients reported relatively stable disinhibition and executive dysfunction, while over half reported a decrease in depression symptoms. Two of the non-responders and one responder endorsed increased apathy despite stable or improved depression symptoms, disinhibition, and executive dysfunction. CONCLUSIONS: Most patients in the current cohort achieved full-or-partial OCD recovery. Yet, 60% of patients also reported significant increases in apathy, despite experiencing a decrease in depression symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology following M-LITT, further investigations of the impact of surgery and lesion location on apathy levels is clearly warranted using objective, quantifiable methods.

Benefits of stereotactic radiosurgical anterior capsulotomy for obsessive-compulsive disorder: a meta-analysis.

OBJECTIVE: Anterior capsulotomy (AC) is a therapeutic option for patients with severe, treatment-resistant obsessive-compulsive disorder (OCD). The procedure can be performed via multiple techniques, with stereotactic radiosurgery (SRS) gaining popularity because of its minimally invasive nature. The risk-benefit profile of AC performed specifically with SRS has not been well characterized. Therefore, the primary objective of this study was to characterize outcomes following stereotactic radiosurgical AC in OCD patients. METHODS: Studies assessing mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores before and after stereotactic radiosurgical AC for OCD were included in this analysis. Inverse-variance fixed-effect modeling was used for pooling, and random-effects estimate of the ratio of means and standard mean differences were calculated at 6 months, 12 months, and the last follow-up for Y-BOCS scores, as well as the last follow-up for the Beck Depression Inventory (BDI)/BDI-II scores. A generalized linear mixed model was used to generate fixed- and random-effects models for categorical outcomes. Univariate random-effects meta-regression was used to evaluate associations between postoperative Y-BOCS scores and study covariates. Adverse events were summed across studies. Publication bias was assessed with Begg's test. RESULTS: Eleven studies with 180 patients were eligible for inclusion. The mean Y-BOCS score decreased from 33.28 to 17.45 at the last-follow up (p < 0.001). Sixty percent of patients were classified as responders and 10% as partial responders, 18% experienced remission, and 4% had worsened Y-BOCS scores. The degree of improvement in the Y-BOCS score correlated with time since surgery (p = 0.046). In the random-effects model, the mean BDI at the last follow-up was not significantly different from that preoperatively. However, in an analysis performed with available paired pre- and postoperative BDI/BDI-II scores, there was significant improvement in the BDI/BDI-II scores postoperatively. Adverse events numbered 235, with headaches, weight change, mood changes, worsened depression/anxiety, and apathy occurring most commonly. CONCLUSIONS: Stereotactic radiosurgical AC is an effective technique for treating OCD. Its efficacy is similar to that of AC performed via other lesioning techniques.

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette's syndrome: Experience and evidence.

OBJECTIVES: To evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette's syndrome (TS). METHODS: This retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. RESULTS: In total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28-74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67-25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26-23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90-15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68-52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5-87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. CONCLUSIONS: Combined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

Ventral targeted anterior capsulotomy for treatment-resistant depression and obsessive-compulsive disorder: A treatment method with cases.

BACKGROUND: Ablative surgery using bilateral anterior capsulotomy (BAC) is an option for treatment resistant depression (TRD) and obsessive-compulsive disorder (TROCD). The location and extent of the lesion within anterior limb of the internal capsule (ALIC) remains uncertain. Accumulating evidence has suggested that the lesion should be located ventrally while limiting the dorsal extent. Our center is now targeting specific fiber tracts within the lower half of the ALIC. METHOD: Presurgical diffusion tensor Magnetic Resonance Imaging (MRI) was used to identify individual fibre tracts within the ventral aspect of the ALIC in the last two patients who underwent BAC at our center. One patient had TRD and the other had both TROCD and TRD. Radiofrequency-induced thermal lesions were created in the identified targets with lesion volumes between 20 and 229 mm3 (average 95 mm3). FINDINGS: Both patients were responders with neither experiencing significant side effects including compromised executive functions. LIMITATIONS: The generalizability of our findings is limited because the outcome is based on two subjects. CONCLUSION: This work suggests that BAC can be individually tailored and more limited to the ventral aspect of the ALIC and is effective and safe for TRD and TROCD. Accumulating data also suggests that to be clinically effective the length of the capsulotomy should be about 10mm. BAC's use may increase with the growing utilization and mastery of magnetic resonance guided focused ultrasound.

Recomendaciones clínicas para la solicitud de evaluación de neurocirugía en el trastorno obsesivo compulsivo / Clinical recommendations for requesting neurosurgical evaluation in obsessive-compulsive disorder

Estas recomendaciones clínicas delinean los criterios utilizados por el Equipo de Cirugía de los Trastornos Psiquiátricos del Hospital de Clínicas para la selección de candidatos a neurocirugía en pacientes con trastorno obsesivo compulsivo grave y refractario al tratamiento convencional. Los criterios de inclusión se enfocan en la cronicidad, la gravedad y la resistencia, considerando procedimientos ablativos o de neuromodulación. La gravedad se evalúa mediante la Escala Yale-Brown Obsessive Compulsive, junto con una evaluación integral del desempeño y la discapacidad. La refractariedad se define como la falta de respuesta, según criterios consensuados, a diversos tratamientos farmacológicos y no farmacológicos respaldados por evidencia científica significativa para el trastorno obsesivo compulsivo. Es esencial realizar una evaluación dimensional del desempeño global y estimar el pronóstico sin intervención quirúrgica. Los criterios de exclusión abarcan comorbilidades graves, trastornos de personalidad específicos y discapacidad intelectual. Además, se especifican pruebas paraclínicas necesarias, incluyendo evaluaciones sanguíneas, serológicas, cardíacas y neurológicas. Se detallan las tablas utilizadas para el registro de información necesaria para la evaluación. Todas las evaluaciones de neurocirugía culminan en un ateneo clínico conjunto entre el Equipo de Cirugía de los Trastornos Psiquiátricos del Hospital de Clínicas y la Unidad Académica de Psiquiatría de la Facultad de Medicina en donde se determinan las estrategias terapéuticas posibles.

These clinical recommendations outline the criteria used by the Psychiatric Disorders Surgery Team for selecting neurosurgery candidates among patients with severe Obsessive Compulsive Disorder refractory to conventional treatment. Inclusion criteria focus on chronicity, severity, and resistance. Ablative procedures or neuromodulation are taken into consideration. Severity is assessed by means of Yale-Brown Obsessive Compulsive Scale, and a comprehensive evaluation of performance and disability. Refractoriness is defined as lack of response, according to consensus criteria, to various pharmacological and non-pharmacological treatments for Obsessive Compulsive Disorder supported by significant scientific evidence. It is essential to conduct a dimensional assessment of overall performance and estimate prognosis without surgical intervention. Exclusion criteria encompass serious comorbidities, specific personality disorders, and intellectual disability. Furthermore, necessary paraclinical tests are specified, including blood, serological, cardiac, and neurological evaluations. Tables used for recording essential information for assessment are detailed. All neurosurgical assessments culminate in a joint clinical discussion of possible therapeutic strategies between the Psychiatric Disorders Surgery Team and the Psychiatry Academic Department (Facultad de Medicina) at the Hospital de Clínicas.

Anterior Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Tractography and Lesion Geometry study.

INTRODUCTION: A bilateral anterior capsulotomy effectively treats refractory obsessive-compulsive disorder (OCD). We investigated the geometry of lesions and disruption of white matter pathways within the anterior limb of the internal capsule (ALIC) in patients with different outcomes. METHODS: In this retrospective study, we analyzed data from 18 patients with refractory OCD who underwent capsulotomies. Patients were grouped into "responders" and "nonresponders" based on the percentage of decrease in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) after surgery. We investigated neurobehavioral adverse effects and analyzed the overlap between lesions and the ventromedial prefrontal (vmPFC) and dorsolateral prefrontal (dlPFC) pathways. Probabilistic maps were constructed to investigate the relationship between lesion location and clinical outcomes. RESULTS: Of the 18 patients who underwent capsulotomies, 12 were responders (>35% improvement in YBOCS), and six were nonresponders. The vmPFC pathway was more involved than the dlPFC pathway in responders (p = 0.01), but no significant difference was observed in nonresponders (p = 0.10). The probabilistic voxel-wise efficacy map showed a relationship between ventral voxels within the ALIC with symptom improvement. Weight gains occurred in 11/18 (61%) patients and could be associated with medial voxels within the ALIC. CONCLUSION: The optimal outcome after capsulotomy in refractory OCD is linked to vmPFC disruption in the ALIC. Medial voxels within the ALIC could be associated with weight gains following capsulotomy.

Cognitive outcomes following functional neurosurgery in refractory OCD patients: a systematic review.

Neurosurgery is a therapeutic option for patients with refractory obsessive-compulsive disorder who do not respond to previous treatments. Although its efficacy in reducing clinical symptomatology has been proven, few studies have analyzed its effects at the cognitive level. The aim of this systematic review was to describe the cognitive outcomes of functional neurosurgery in patients that went through capsulotomies or cingulotomies. PubMed, Medline, Scopus, PsycInfo, PsyArticles, and Web of Knowledge were searched for studies reporting cognitive outcomes in refractory obsessive-compulsive patients after capsulotomies and cingulotomies. The risk of bias was assessed with the Assessment Tool for Before-After (Pre-Post) Studies With No Control Group tool; 13 studies met inclusion criteria, including 205 refractory obsessive-compulsive disorder patients for both surgical procedures. Results showed a substantial number of studies that did report significant cognitive improvement after surgery, being this improvement specially related to memory and executive functions. The second-most frequent finding is the maintenance of cognitive performance (nor improvement or worsening). From a neuropsychological point of view, this outcome might be considered a success, given that it is accompanied by amelioration of obsessive-compulsive symptoms. Subtle cognitive adverse effects have also been reported. Neurosurgery procedures appear to be safe from a cognitive point of view. Methodological issues must be improved to draw clearer conclusions, but capsulotomies and cingulotomies constitute an effective alternative treatment for refractory obsessive-compulsive disorder patients.

Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Contemporary Role of Stereotactic Radiosurgery for Psychiatric Disorders.

Psychiatric disorders are the hidden pandemic of the current century. Despite major advances in medical management, the options for treatment are still limited. Neurosurgical intervention is effective for certain refractory psychiatric illnesses and the options range from stimulation surgeries to precise disconnection procedures influencing the neuronal network. Literature regarding stereotactic radiosurgery (SRS) is now enriched with successful treatment of obsessive compulsive disorder, major depression disorder, and anorexia nervosa. These procedures by reducing compulsions, obsessions, depression, and anxiety, improve substantially the quality of life for patients with a good safety profile. It is a valid treatment alternative for a selected group of patients who otherwise have no therapeutic options for whom the neurosurgical intervention is the only hope. It is also cost effective and highly reproducible among specialists. These procedures are adjuvant to the medical and behavioural treatment of psychiatric disorders. In this study the Contemporary role of Stereotactic radiosurgery is reviewed starting with relevant history of psychosurgery followed by individual psychiatric disorders.

Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data.

OBJECTIVE: Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). METHODS: A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. RESULTS: Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively). CONCLUSIONS: Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

Cost-effectiveness analysis of radiosurgical capsulotomy versus treatment as usual for treatment-resistant obsessive-compulsive disorder.

OBJECTIVE: Stereotactic radiosurgical capsulotomy (SRS-C) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (TROCD). Unlike other procedures such as deep brain stimulation and radiofrequency ablation, the cost-effectiveness of SRS-C for TROCD has not been investigated. The authors herein report the first cost-effectiveness analysis of SRS-C for TROCD. METHODS: Using a decision analytic model, the authors compared the cost-effectiveness of SRS-C to treatment as usual (TAU) for TROCD. Treatment response and complication rates were derived from a review of relevant clinical trials. Published algorithms were used to convert Yale-Brown Obsessive Compulsive Scale scores into utility scores reflecting improvements in quality of life. Costs were approached from the healthcare sector perspective and were drawn from Medicare reimbursement rates and available healthcare economics data. A Monte Carlo simulation and probabilistic sensitivity analysis were performed to estimate the incremental cost-effectiveness ratio. RESULTS: One hundred fifty-eight TROCD patients across 9 studies who had undergone SRS-C and had at least 36 months of follow-up were included in the model. Compared to TAU, SRS-C was more cost-effective, with an estimated incremental cost-effectiveness ratio of $28,960 per quality-adjusted life year (QALY) gained. Within the 3-year time horizon, net QALYs gained were greater in the SRS-C group than the TAU group by 0.27 (95% CI 0.2698-0.2702, p < 0.0001). At willingness-to-pay thresholds of $50,000 and $100,000 per QALY, the Monte Carlo simulation revealed that SRS-C was more cost-effective than TAU in 83% and 100% of iterations, respectively. CONCLUSIONS: Compared to TAU, SRS-C for TROCD is more cost-effective under a range of possible cost and effectiveness values.

Gamma knife radiosurgery versus deep brain stimulation for treatment-refractory depression and obsessive-compulsive disorder: A brief comparative summary.

Both gamma knife surgery (GKS) and deep brain stimulation (DBS) have documented success in management of treatment-refractory major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), but there are no formal randomized controlled trials to compare these treatment modalities in cases of psychiatric illnesses. In this brief review, comparison of GKS and DBS for management of MDD and OCD was done with regard to their efficacy, accompanying risks, reversibility of therapeutic effects, costs, availability, and daily life issues. Currently available evidence does not support the superiority of either evaluated treatment modality over each other in terms of clinical efficacy in cases of MDD and OCD. Nevertheless, with regard to risks, costs, device maintenance, and daily life issues, GKS definitely seems more advantageous. Reversibility of therapeutic effects of DBS is certainly highly attractive, while may be a bit overhyped. In any case, synergy between GKS and DBS for management of mental illnesses lies in the continuing pursuit of improvement and raising the bar of excellence.

Gamma Knife capsulotomy for correction of obsessive-compulsive symptoms in a patient with schizophrenia: Case report.

The treatment of mental illnesses that are resistant to conservative therapy poses a serious problem. Surgical methods with proven efficacy have been proposed for only a small group of psychiatric diseases, while in practice non-classical clinical situations are seen rather often. A 36-year-old man with a 18-year history of "schizophrenia with a predominant obsessive-compulsive syndrome" was referred to the Burdenko National Medical Research Center of Neurosurgery for consideration of neurosurgical treatment. Based on results of longitudinal independent evaluations of the patient in several specialized clinical centers the disease was considered resistant to medical therapy. Radiosurgical procedure was performed by means of Leksell Gamma Knife Perfexion™ (Elekta AB; Stockholm, Sweden). Ventral portion of the anterior limb of internal capsule was targeted with two 4-mm isocenters on each side, with prescription dose at 50% isodose line of 80 Gy and a maximal dose of 160 Gy. No obvious complications or side effects were noted during 13-month follow-up after radiosurgery. Gradual clinical improvement was observed with 25% reduction of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at 13 months after treatment. Similarly, the Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores decreased by 24% and 58%, respectively. This is the first published case of radiosurgical treatment of a psychiatric disorder in Russia. It demonstrates the potential efficacy of Gamma Knife capsulotomy for non-classical forms of obsessive-compulsive disorder comorbid with schizophrenia. Nevertheless, definitive conclusions about the reliability of this radiosurgical indication can only be made based on the results of larger studies.

Surgery of autism: Is it possible?

Autism spectrum disorder (ASD) is a developmental disability of the brain that can be associated to severe conductual alterations, such as self or heteroaggression and obsessive and compulsive behavior. Many of these patients do not improve with any pharmacological or behavioral therapy and represent a major social problem. We describe the outcome of patients with ASD, treated with radiofrequency brain lesions combined with Gamma Knife radiosurgery for therapy-resistant aggressiveness, obsessive thoughts, and compulsions. The ASD adapted YBOCS, PCQ and EAE scales assessed the therapeutic effect on symptoms. All patients had a significant reduction of their symptoms (YBOCS:34 and 22 PCQ 42 and 35, EAE 11 and 5.5, respectively), although all needed more than one treatment to maintain this improvement. The treatments resulted very safe for the patients and their neurological status has not change. We conclude that in these patients after surgery, there is a marked improvement in behavior, quality of life and relationship with the environment, with no evidence of secondary damage. Changes in connectivity might mediate the clinical improvement, although it is necessary to confirm these results with further studies.

Noninvasive Capsulotomy for Refractory Depression by Frameless Stereotactic Radiosurgery.

PURPOSE: Effective treatment options for refractory depression are needed. Recent advancements permit both precise ablative radiation and functional neurologic connectome analysis using standard magnetic resonance imaging. We combined these innovations to perform stereotactic radiosurgical capsulotomy for the treatment of medically refractory major depressive disorder and study connectome response using a novel tractography-based approach. METHODS AND MATERIALS: Patients with medically refractory depression were enrolled on a prospective pilot single-arm observational trial from 2020 to 2021 at a single academic tertiary referral center. Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery. Beck's Depression Inventory measured efficacy. Montreal Cognitive Assessment evaluated cognition. RESULTS: Three patients were enrolled. Depression burden was improved by 88% at 12-month follow-up and by 55% at 18-month follow-up for patient 1 and 2, respectively. Patient 1 discontinued ketamine therapy, and patient 2 discontinued electroconvulsive therapy. Patient 3 reported global improvement in symptoms and function at 3 months. All 3 patients had reduction or resolution of suicidal ideation. No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior after treatment. Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural reorganization in the connectome. Connectome change was consistent between patients. Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression. The diversity and magnitude of connectome change may correlate with degree of clinical response. CONCLUSIONS: In 3 patients with refractory depression, radiosurgical capsulotomy significantly reduced the burden of depression. Functional connectome reorganization offers neurobiological evidence to support further investigations of the role of radiosurgery in depression.

Modern Gamma Knife radiosurgery for management of psychiatric disorders.

Psychiatric disorders result in great suffering of affected patients, who often have rather limited treatment options. In cases refractory to standard medical and behavioral therapy, interventional procedures may be the only feasible solution. The authors experience with Gamma Knife bilateral cingulotomy for treatment-resistant major depression disorder (5 cases) and anorexia nervosa (6 cases), and bilateral anterior capsulotomy for severe obsessive-compulsive disorder (10 cases) shows that such radiosurgical techniques may be applied both effectively and safely. During post-treatment follow-up, the vast majority of patients demonstrated gradual reduction of psychiatric symptoms and improvement of the quality of life, which was confirmed by results of regular neuropsychological testing and imaging examinations. No major side effect was observed in any case. More active application of radiosurgery (using standardized technique) for management of mental illnesses in various Gamma Knife centers worldwide should be encouraged.

Gamma Knife radiosurgery for obsessive compulsive disorder.

Gamma Knife radiosurgical capsulotomy has been performed for over 40 years as a rarely used surgical intervention for the treatment of obsessive-compulsive disorder. Over time, the procedure has evolved in many ways with most significant modifications being made in target location, number of isocenters and prescribed dose, subsequently producing changes in lesion size and geometry. Long-term clinical response data and adverse outcomes to the earlier empiric treatment parameters have resulted in shifting the target from its initial location within the midpoint of the anterior limb of internal capsule to a currently used point that includes its most ventral portion as well as the ventral striatum. This led to the contemporary Gamma Knife ventral capsulotomy procedure that focuses on ventral capsule/ventral striatum. Many of the early studies, despite demonstrating efficacy in some patients, were complicated by clinically relevant radiation-induced adverse effects. More recent studies have demonstrated strong efficacy with diminished adverse effects with well-placed lesions created at lower radiation doses. Advances in neuroimaging technology such as diffusion tensor imaging (DTI) based fiber tracking may provide further insight into precisely targeting of the ventral capsule/striatum based on patient-specific variations in white matter connectivity.

Differential assessment of frontally-mediated behaviors between self- and informant-report in patients with obsessive-compulsive disorder following gamma ventral capsulotomy.

Obsessive-Compulsive Disorder (OCD) is a debilitating disorder causing marked distress and functional impairment. While advances in behavioral and pharmacotherapies have been effective for a majority of patients with OCD, 10-30% remain treatment refractory and severely impaired. For a subset of treatment-resistant individuals with the most severe and disabling (intractable) illness, gamma ventral capsulotomy (GVC) appears effective in reducing OCD symptoms and functional impairment. However, the effects of the ventral internal capsule lesion via GVC surgery on executive function in everyday life have been minimally investigated. Examining behavioral outcomes of GVC also provides a rare opportunity to probe the functional importance of the ventral prefrontal-subcortical connections of the internal capsule white matter tract in a relatively homogenous sample of patients with comparable white matter lesions. The present study investigated changes in frontally-mediated behaviors, measured by the Frontal Systems Behavior Scale (FrSBe), following GVC in 45 individuals with severe and otherwise intractable OCD, as rated by patients themselves and family members. Linear mixed effects models revealed a significant improvement in patient self-ratings on the FrSBe after surgery, while family ratings did not significantly change. Interestingly, improvement on the FrSBe for both self and family raters was significantly correlated with improvement in OCD symptomatology post-surgery, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). At the group level, we found no evidence of decline in frontally-mediated behaviors assessed by the FrSBe as a result of focal white matter disconnection via GVC. However, we cannot rule out the possibility that placebo effects or compromised patient self-awareness or insight contributed to the significant improvement in self ratings. Our measures may also have limited sensitivity to more selective impairments that could result from a small lesion to the ventral internal capsule. The present study demonstrates the need for detailed investigation of cognitive and behavioral changes as important factors when considering GVC as a viable treatment option for patients with refractory OCD.

The prefrontal cortex and neurosurgical treatment for intractable OCD.

Over the past two decades, circuit-based neurosurgical procedures have gained increasing acceptance as a safe and efficacious approach to the treatment of the intractable obsessive-compulsive disorder (OCD). Lesions and deep brain stimulation (DBS) of the longitudinal corticofugal white matter tracts connecting the prefrontal cortex with the striatum, thalamus, subthalamic nucleus (STN), and brainstem implicate orbitofrontal, medial prefrontal, frontopolar, and ventrolateral cortical networks in the symptoms underlying OCD. The highly parallel distributed nature of these networks may explain the relative lack of adverse effects observed following surgery. Additional pre-post studies of cognitive tasks in more surgical patients are needed to confirm the role of these networks in OCD and to define therapeutic responses to surgical intervention.

Potential optimization of focused ultrasound capsulotomy for obsessive compulsive disorder.

Obsessive-compulsive disorder is a debilitating and often refractory psychiatric disorder. Magnetic resonance-guided focused ultrasound is a novel, minimally invasive neuromodulatory technique that has shown promise in treating this condition. We investigated the relationship between lesion location and long-term outcome in patients with obsessive-compulsive disorder treated with focused ultrasound to discern the optimal lesion location and elucidate the efficacious network underlying symptom alleviation. Postoperative images of 11 patients who underwent focused ultrasound capsulotomy were used to correlate lesion characteristics with symptom improvement at 1-year follow-up. Normative resting-state functional MRI and normative diffusion MRI-based tractography analyses were used to determine the networks associated with successful lesions. Patients with obsessive-compulsive disorder treated with inferior thalamic peduncle deep brain stimulation (n = 5) and lesions from the literature implicated in obsessive-compulsive disorder (n = 18) were used for external validation. Successful long-term relief of obsessive-compulsive disorder was associated with lesions that included a specific area in the dorsal anterior limb of the internal capsule. Normative resting-state functional MRI analysis showed that lesion engagement of areas 24 and 46 was significantly associated with clinical outcomes (R = 0.79, P = 0.004). The key role of areas 24 and 46 was confirmed by (i) normative diffusion MRI-based tractography analysis, showing that streamlines associated with better outcome projected to these areas; (ii) association of these areas with outcomes in patients receiving inferior thalamic peduncle deep brain stimulation (R = 0.83, P = 0.003); and (iii) the connectedness of these areas to obsessive-compulsive disorder-causing lesions, as identified using literature-based lesion network mapping. These results provide considerations for target improvement, outlining the specific area of the internal capsule critical for successful magnetic resonance-guided focused ultrasound outcome and demonstrating that discrete frontal areas are involved in symptom relief. This could help refine focused ultrasound treatment for obsessive-compulsive disorder and provide a network-based rationale for potential alternative targets.