Repetitive Negative Thinking-Specific and -Nonspecific White Matter Tracts Engaged by Historical Psychosurgical Targets for Depression.

BACKGROUND: Repetitive negative thinking (RNT) is a frequent symptom of major depressive disorder (MDD) that is associated with poor outcomes and treatment resistance. While most studies on RNT have focused on structural and functional characteristics of gray matter, this study aimed to examine the association between white matter (WM) tracts and interindividual variability in RNT. METHODS: A probabilistic tractography approach was used to characterize differences in the size and anatomical trajectory of WM fibers traversing psychosurgery targets historically useful in the treatment of MDD (anterior capsulotomy, anterior cingulotomy, and subcaudate tractotomy) in patients with MDD and low (n = 53) or high (n = 52) RNT, and healthy control subjects (n = 54). MDD samples were propensity matched on depression and anxiety severity and demographics. RESULTS: WM tracts traversing left hemisphere targets and reaching the ventral anterior body of the corpus callosum (thus extending to contralateral regions) were larger in the high-RNT MDD group compared with low-RNT (effect size D = 0.27, p = .042) and healthy control (D = 0.23, p = .02) groups. MDD was associated with greater size of tracts that converge onto the right medial orbitofrontal cortex regardless of RNT intensity. Other RNT-nonspecific findings in MDD involved tracts reaching the left primary motor and right primary somatosensory cortices. CONCLUSIONS: This study provides the first evidence to our knowledge that WM connectivity patterns, which could become targets of intervention, differ between high- and low-RNT participants with MDD. These WM differences extend to circuits that are not specific to RNT, possibly subserving reward mechanisms and psychomotor activity.

The effects of major depression disorder on neurogenic thoracic outlet syndrome surgery outcomes.

OBJECTIVES: Thoracic outlet syndrome (TOS) is a group of disorders caused by impingement of the neurovascular structures at the thoracic outlet. Neurogenic TOS (nTOS), which is thought to be caused by a compression of the brachial plexus, accounts for more than 90% of the cases. Although treatment for nTOS is successful through physiotherapy and/or surgical decompression, little is known about the impact of psychosocial factors, namely, major depressive disorder (MDD), on postoperative outcomes such as non-routine discharge (NRD). Here, we assess whether MDD predicts the type of discharge following nTOS surgical intervention. METHODS: A retrospective analysis of the National Inpatient Sample database from the years 2005-2018 was performed. Using the International Classification of Diseases Clinical Modification, Ninth and Tenth revisions, patients who underwent a surgical intervention for nTOS were identified. Our primary outcome was to investigate the effects of MDD on nTOS patient disposition status after surgical management; secondary outcomes included analysis of total hospital charges and length of stay. NRD was defined as anything beyond discharge home without healthcare services. Univariate and multivariable logistic regression analyses were conducted to assess MDD and other potential independent predictors of NRD and prolonged hospital stay (> 2 days) following surgical intervention. RESULTS: A total of 6099 patients were identified: 596 (9.77%) patients with MDD and 5503 (90.23%) without MDD. On average, patients with MDD were older (39.6 ± 12.0 years vs. 36.0 ± 13.0 years; p < 0.001), female (80.7% vs. 63.5%; p < 0.001), white (89.6% vs. 85.6%; p = 0.030), and on Medicare (9.6% vs 5.2%; p < 0.001). Univariate and multivariable logistic regression models identified MDD as an independent risk factor associated with a higher risk of NRD (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.0-2.2). Additionally, chronic kidney disease (aOR, 2.60; 95% CI, 1.2-5.4), postoperative complications (aOR, 1.87; 95% CI, 1.2-2.9), and Medicare (aOR, 2.95; 95% CI, 1.9-4.7) were statistically significant predictors for higher risk of NRD. However, MDD was not associated with prolonged hospital stay (aOR, 1.00; 95% CI, 0.8-1.2) or higher median of total charges (MDD group: $27,867 vs. non-MDD group: $28,123; p = 0.799). CONCLUSION: Comorbid MDD was strongly associated with higher NRD rates following nTOS surgical intervention. MDD had no significant impact on length of hospital stay or total hospital charges. Additional prospective research is necessary in order to better evaluate the impact of MDD in patients with nTOS.

Pre-existing Mental Health Diagnoses Are Associated With Higher Rates of Postoperative Complications, Readmissions, and Reoperations Following Arthroscopic Rotator Cuff Repair.

PURPOSE: To investigate the association between preoperative mental health disorders and postoperative complications, readmissions, and ipsilateral revision procedures among patients undergoing arthroscopic rotator cuff repair (RCR). METHODS: A retrospective cohort study from 2010 to 2020 was performed using the PearlDiver database. Current Procedural Terminology and International Classification of Diseases codes were used to compare patients with and without mental health disorders who underwent arthroscopic RCR. Mental health disorders evaluated in this study include depressive disorder, major depressive disorder, major depressive affective disorder, bipolar disorder, dysthymic disorder, adjustment disorder, separation anxiety disorder, and posttraumatic stress disorder. Patients were matched at a 1:1 ratio based on age, sex, Charlson Comorbidity Index, body mass index, and tobacco use. Rates of complications and subsequent surgeries were compared between patients with and without a preoperative diagnosis of a mental health disorder. RESULTS: The 1-year preoperative prevalence of a mental health disorder from 2010 to 2020 was 14.6%. After 1:1 matching, patients with a mental health disorder who underwent arthroscopic RCR were nearly twice as likely to undergo a revision procedure (odds ratio 1.94, 95% confidence interval 1.76-2.14, P < .001) and more than twice as likely to experience conversion to shoulder arthroplasty (odds ratio 2.29, 95% confidence interval 1.88-2.80, P < .001) within 2 years of initial arthroscopy when compared with patients without a mental disorder. Patients with a mental disorder also experienced increased risk for 90-day readmission (1.9% vs 0%, P < .001) as well as multiple postoperative medical complications. CONCLUSIONS: Patients with pre-existing mental health diagnoses experience increased rates of 90-day postoperative complications and readmissions following arthroscopic RCR. In addition, patients with mental health diagnoses are more likely to undergo revision repair and conversion to shoulder arthroplasty within 2 years of the index procedure. LEVEL OF EVIDENCE: Level III.

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.

Neuromodulation Strategies for the Treatment of Depression.

For many decades, psychiatric treatment has been primarily guided by two major paradigms of psychopathology: a neurochemical paradigm leading to the development of medications and a psychological paradigm resulting in the development of psychotherapies. A third paradigm positing that psychiatric dysfunction results from abnormal communication within a network of brain regions that regulate mood, thought, and behavior has gained increased attention over the past several years and underlies the development of multiple neuromodulation and neurostimulation therapies. This neural circuit paradigm is not new. In the late 19th and early 20th centuries, it was a common way of understanding psychiatric illness and led to several of our earliest somatic therapies. However, with the rise of effective medications and evidence-based psychotherapies, this paradigm went mostly dormant. Its recent reemergence resulted from a growing recognition that medications and psychotherapy leave many patients inadequately treated, along with technological advances that have revolutionized our ability to understand and modulate the neural circuitry involved in psychiatric disorders. In this overview, the authors review the history and current state of neuromodulation for psychiatric illness and specifically focus on these approaches as a treatment for depression, as this has been the primary indication for these interventions over time.

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.

Technology of deep brain stimulation: current status and future directions.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.

Deep brain stimulation telemedicine programming during the COVID-19 pandemic: treatment of patients with psychiatric disorders.

OBJECTIVE: The ongoing coronavirus disease 2019 (COVID-19) pandemic has considerably affected the delivery of postoperative care to patients who have undergone deep brain stimulation (DBS) surgery. DBS teleprogramming technology was developed and deployed in China before the COVID-19 outbreak. In this report, the authors share their experiences with telemedical DBS treatment of patients with psychiatric disorders during the COVID-19 outbreak. METHODS: Four patients (2 with obsessive-compulsive disorder, 1 with major depressive disorder, and 1 with anorexia nervosa) underwent DBS surgery at Ruijin Hospital and received continuous postoperative DBS telemedicine case management from January 2020 to July 2020. DBS teleprogramming, individualized psychological support, and medical consultations were provided via the authors' DBS telemedicine platform, which also incorporated a synchronous real-time video communication system. RESULTS: Forty-five DBS telemedicine sessions were conducted; there was no unexpected loss of network connection during the sessions. Of these, 28 sessions involved DBS teleprogramming. Adjustments were made to the stimulation voltage, frequency, pulse width, and contact site in 21, 12, 9, and 9 sessions, respectively. Psychological support and troubleshooting were provided during the remaining telemedicine sessions. Modest to substantial clinical improvements after DBS surgery were observed in some but not all patients, whereas stimulation-related side effects were reported by 2 patients and included reversible sleep and mood problems, headache, and a sensation of heat. CONCLUSIONS: DBS telemedicine seems to offer a feasible, safe, and efficient strategy for maintaining the delivery of medical care to psychiatric patients during the COVID-19 outbreak. The authors propose that implementation of a comprehensive DBS telemedicine system, which combines DBS teleprogramming with psychological counseling, medical consultations, and medication prescriptions and delivery, could be an efficient and effective approach to manage the mental health and quality of life of patients with psychiatric disorders during future local or global public health crises.

Effect of Comorbid Depression on Surgical Outcomes After Craniotomy for Malignant Brain Tumors: A Nationwide Readmission Database Analysis.

OBJECTIVE: Quality of life is paramount in patients with advanced cancer and may be adversely affected by comorbid depression. We hypothesized that comorbid depression is associated with higher rates of postoperative complications, worse functional outcomes, and higher rates of readmission after craniotomy for resection of malignant intracranial tumors. METHODS: The National Readmissions Database was queried from 2010 to 2014 to identify adult patients undergoing craniotomy for malignant brain tumor resection. The primary psychiatric disease assessed was major depressive disorder (MDD). Outcomes evaluated included neurologic or other major complications, incidence of nonroutine discharge, and unplanned readmission at 30 and 90 days. RESULTS: Of the 57,621 craniotomies for malignant neoplasms included in the analysis, 11.32% of patients had clinically diagnosed MDD. The presence of MDD was associated with nonroutine discharge (odds ratio, 1.10-125; P < 0.0001) as well as higher rates of neurologic complications (odds ratio, 1.03-1.18; P = 0.003). No association between MDD and 30-day or 90-day readmissions was noted. Patients with major All Patient Refined Diagnosis Related Groups severity and index length of stay >7 days experienced higher rates of 30-day and 90-day readmissions. CONCLUSIONS: There is a clinically significant rate of comorbid MDD in patients with malignant intracranial tumors, and MDD is associated with worse perioperative outcomes. Given the wealth of behavioral and pharmaceutical therapies available, MDD is a modifiable risk factor in this cohort that clinicians should be vigilant in screening for and initiating appropriate treatment protocols.

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.

Machine learning-aided personalized DTI tractographic planning for deep brain stimulation of the superolateral medial forebrain bundle using HAMLET.

BACKGROUND: Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI definition), and has to be regarded as subjective. We aimed to develop an objective but patient-specific tracking of the slMFB which at the same time allows the use of a commercial surgical planning system in the context of deep brain stimulation. METHODS: The HAMLET (Hierarchical Harmonic Filters for Learning Tracts from Diffusion MRI) machine learning approach was introduced into the standardized workflow of slMFB DBS tractographic planning on the basis of patient-specific dMRI. Rendition of the slMFB with HAMLET serves as an objective comparison for the refinement of the deterministic tracking procedure. Our application focuses on the tractographic planning of DBS (N = 8) for major depression and OCD. RESULTS: Previous results have shown that only fibers belonging to the ventral tegmental area to prefrontal/orbitofrontal axis should be targeted. With the proposed technique, the deterministic tracking approach, that serves as the surgical planning data, can be refined, over-sprouting fibers are eliminated, bundle thickness is reduced in the target region, and thereby probably a more accurate targeting is facilitated. The HAMLET-driven method is meant to achieve a more objective surgical fiber display of the slMFB with deterministic tractography. CONCLUSIONS: The approach allows overlying the results of patient-specific planning from two different approaches (manual deterministic and machine learning HAMLET). HAMLET shows the slMFB as a volume and thus serves as an objective tracking corridor. It helps to refine results from deterministic tracking in the surgical workspace without interfering with any part of the standard software solution. We have now included this workflow in our daily clinical experimental work on slMFB DBS for psychiatric indications.

Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression.

Background: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported. Objective: To give a detailed description of the surgical technique for DBS of the superolateral branch of the medial forebrain bundle (slMFB) in MDD. Methods: Surgical experience from bilateral implantation procedures in n = 24 patients with MDD is reported. The detailed procedure of tractography-assisted targeting together with detailed electrophysiology in 144 trajectories in the target region (recording and stimulation) is described. Achieved electrode positions were evaluated based on postoperative helical CT and fused to preoperative high resolution anatomical magnetic resonance imaging (MRI; Philips Medical Systems, Best, Netherlands), including the pre-operative diffusion tensor imaging (DTI) tractographic information (StealthViz DTI, Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP) coordinates of effective contact (EC) location, together with angles of entry into the target region were evaluated. To investigate incidental stimulation of surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined, located between these structures (based on MRI criteria in T2) and evaluated with respect to EC locations. Results: Bilateral slMFB DBS was performed in all patients. We identified an electrophysiological environment (defined by autonomic reaction, passive microelectrode recording, acute effects and oculomotor effects) that helps to identify the proper target site on the operation table. Postoperative MCP-evaluation of effective contacts (EC) shows a significant variability with respect to localization. Evaluation of the TT shows that responders will typically have their active contacts inside the triangle and that surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a predominant white matter stimulation. The individual EC position within the triangle cannot be predicted and is based on individual slMFB (tractography) geometry. There was one intracranial bleeding (FORESEE I study) during a first implantation attempt in a patient who later received full bilateral implantation. Typical oculomotor side effects are idiosyncratic for the target region and at inferior contacts. Conclusion: The detailed surgical procedure of slMFB DBS implantation has not been described before. The slMFB emerges as an interesting region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it has only been successfully researched in open label clinical case series and in 15 patients published. Stimulation probably achieves its effect through direct white-matter modulation of slMFB fibers. The surgical implantation comprises a standardized protocol combining tractographic imaging based on DTI, targeting and electrophysiological evaluation of the target region. To this end, slMFB DBS surgery is in technical aspects comparable to typical movement disorder surgery. In our view, slMFB DBS should only be performed under tractographic assistance.

The History and Future of Ablative Neurosurgery for Major Depressive Disorder.

BACKGROUND: There is an urgent need to develop safe and effective treatments for patients with treatment-resistant depression (TRD). Several neurosurgical procedures have been developed to treat the dysfunctional brain circuits implicated in major depression. OBJECTIVES: This review describes the most common ablative procedures used to treat major depressive disorder: anterior cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior capsulotomy. The efficacy and safety of each are discussed and compared with other current and emerging modalities, including deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS). METHODS: The PubMed and MEDLINE electronic databases were used in this study, through July 2016. Keywords, including "treatment resistant depression," and "ablative neurosurgery," etc. were used to generate reference hits. RESULTS: Approximately a third to half of patients who underwent ablative procedures achieved a treatment response and/or remission. The efficacy and safety profiles corresponding to both ablative procedures and DBS were very similar. CONCLUSIONS: The longitudinal experience with ablative procedures shows that there remains an important role for accurate, discrete lesions in disrupting affective circuitry in the treatment of TRD. New modalities, such as MRgFUS, have the potential to further improve the accuracy of ablative procedures, while enhancing safety by obviating the need for open brain surgery.

Neurosurgery for mental disorders: a review.

Neurosurgical interventions date back to ancient civilization, 5100 BC through a practice known as trephination. Due to past abuse and ethical considerations, neurosurgical interventions in psychiatry remain a controversial issue. This article aims to review the different surgical techniques and their current application in the treatment of psychiatric disorders. The U.S Food and Drug Administration (FDA) gave its approval for vagal nerve stimulation (VNS) for the management of treatment-resistant depression in 2005 and deep brain stimulation (DBS) for refractory obsessive-compulsive disorders (OCD) in 2009. These invasive but non destructive techniques represent the future of neurosurgery for mental disorder.

Surgery for psychiatric disorders.

Surgery in psychiatric disorders has a long history and has regained momentum in the past few decades with deep brain stimulation (DBS). DBS is an adjustable and reversible neurosurgical intervention using implanted electrodes to deliver controlled electrical pulses to targeted areas of the brain. It holds great promise for therapy-refractory obsessive-compulsive disorder. Several double-blind controlled and open trials have been conducted and the response rate is estimated around 54%. Open trials have shown encouraging results with DBS for therapy-refractory depression and case reports have shown potential effects of DBS on addiction. Another promising indication is Tourette syndrome, where potential efficacy of DBS is shown by several case series and a few controlled trials. Further research should focus on optimizing DBS with respect to target location and increasing the number of controlled double-blinded trials. In addition, new indications for DBS and new target options should be explored in preclinical research.