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.

Tractography-Guided Anterior Capsulotomy for Major Depression and Obsessive-Compulsive Disorder: Targeting the Emotion Network.

BACKGROUND: Bilateral anterior capsulotomy (BAC) is an effective surgical option for patients with treatment-resistant major depression (TRMD) and treatment-resistant obsessive-compulsive disorder (TROCD). The size of the lesion and its precise dorsal-ventral location within the anterior limb of the internal capsule (ALIC) remain undefined. OBJECTIVE: To present a method to identify the trajectories of the associative and limbic white matter pathways within the ALIC for targeting in BAC surgery. METHODS: Using high-definition tractography, we prospectively tested the feasibility of this method in 2 patients with TRMD and TROCD to tailor the capsulotomy lesion to their limbic pathway. RESULTS: The trajectories of the associative and limbic pathways were identified in the ALIC of both patients and we targeted the limbic pathways by defining the dorsal limit of the lesion in a way to minimize the damage to the associative pathways. The final lesions were smaller than those that have been previously published. This individualized procedure was associated with long-term benefit in both patients. CONCLUSION: Tractography-guided capsulotomy is feasible and was associated with long-term benefit in patients with TRMD and TROCD.

An Analysis of Clinical Outcome and Tractography following Bilateral Anterior Capsulotomy for Depression.

INTRODUCTION: Bilateral anterior capsulotomy (BAC) is an effective surgical procedure for patients with treatment-resistant major depression (TRMD). In this work, we analyze the connectivity of the BAC lesions to identify connectivity "fingerprints" associated with clinical outcomes in patients with TRMD. METHODS: We performed a retrospective study of ten patients following BAC surgery. These patients were divided into "responders" and "non-responders" based on the relative change in the Beck depression inventory (BDI) score after surgery. We generated the dorsolateral prefrontal associative (DLPFC) pathways and the ventromedial prefrontal limbic (vmPFC) pathways going through the anterior limb of the internal capsule and analyzed if the overlap of the BAC lesions with these pathways was associated with either outcome. Finally, we used the BAC lesions of our patients to generate group-averaged connectivity "fingerprints" associated with either outcome. RESULTS: Six patients were responders (≥50% improvement in BDI), four patients were non-responders (<50% improvement). No significant impairments were found in most neuropsychological tests after surgery. The overlap analysis showed that in the responder group, there was less involvement of the DLPFC pathways than the vmPFC pathways (p = 0.001). Conversely, in the non-responder group, there was no significant difference between the involvement of both pathways (p = 0.157). The responder and non-responder connectivity fingerprint showed significant connections with the vmPFC limbic areas. However, the non-responder connectivity fingerprint also showed stronger connectivity to associative areas including the DLPFC and lateral orbitofrontal cortices. CONCLUSIONS: The optimum outcome following BAC surgery in this cohort was associated with interruption of vmPFC pathways and the relative preservation of DLPFC pathways.

Long-term neuropsychological safety of subgenual cingulate gyrus deep brain stimulation for treatment-resistant depression.

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) is a promising investigational intervention for treatment-resistant depression (TRD), but long-term outcome data are limited. Serial neuropsychological evaluations, using a comprehensive battery, were conducted on four subjects with TRD prior to surgery, and up to 42 months post-operatively. Reliable change methodology suggested general stability and/or select statistically reliable improvement in cognitive abilities over time. This is the first known set of multi-year neuropsychological follow-up data for SCG DBS for TRD. Observed improvements are likely attributable to reduced depressive symptomatology, recovery of functional capacities, and/or specific practice effects of repeated assessment.