Structural connectivity modifications following deep brain stimulation of the subcallosal cingulate and nucleus accumbens in severe anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a mental health disorder characterized by significant weight loss and associated medical and psychological comorbidities. Conventional treatments for severe AN have shown limited effectiveness, leading to the exploration of novel interventional strategies, including deep brain stimulation (DBS). However, the neural mechanisms driving DBS interventions, particularly in psychiatric conditions, remain uncertain. This study aims to address this knowledge gap by examining changes in structural connectivity in patients with severe AN before and after DBS. METHODS: Sixteen participants, including eight patients with AN and eight controls, underwent baseline T1-weigthed and diffusion tensor imaging (DTI) acquisitions. Patients received DBS targeting either the subcallosal cingulate (DBS-SCC, N = 4) or the nucleus accumbens (DBS-NAcc, N = 4) based on psychiatric comorbidities and AN subtype. Post-DBS neuroimaging evaluation was conducted in four patients. Data analyses were performed to compare structural connectivity between patients and controls and to assess connectivity changes after DBS intervention. RESULTS: Baseline findings revealed that structural connectivity is significantly reduced in patients with AN compared to controls, mainly regarding callosal and subcallosal white matter (WM) tracts. Furthermore, pre- vs. post-DBS analyses in AN identified a specific increase after the intervention in two WM tracts: the anterior thalamic radiation and the superior longitudinal fasciculus-parietal bundle. CONCLUSIONS: This study supports that structural connectivity is highly compromised in severe AN. Moreover, this investigation preliminarily reveals that after DBS of the SCC and NAcc in severe AN, there are WM modifications. These microstructural plasticity adaptations may signify a mechanistic underpinning of DBS in this psychiatric disorder.

Exploring arterial anatomy of the internal capsule: an analysis of the deep vascular structures and related white matter pathways.

BACKGROUND AND OBJECTIVES: The internal capsule is supplied by perforators originating from the internal carotid artery, middle cerebral artery, anterior choroidal artery and anterior cerebral artery. The aim of this study is to examine the vascular anatomy of the internal capsule, along with its related white matter anatomy, in order to prevent potential risks and complications during surgical interventions. METHODS: Twenty injected hemispheres prepared according to the Klingler method were dissected. Dissections were photographed at each stage. The findings obtained from the dissections were illustrated to make them more understandable. Additionally, the origins of the arteries involved in the vascularization of the internal capsule, their distances to bifurcations, and variations in supplying territories have been thoroughly examined. RESULTS: The insular cortex and the branches of the middle cerebral artery on the insula and operculum were observed. Following decortication of the insular cortex, the extreme capsule, claustrum, external capsule, putamen and globus pallidus structures were exposed. The internal capsule is shown together with the lenticulostriate arteries running on the anterior, genu and posterior limbs. Perforators supplying the internal capsule originated from the middle cerebral artery, anterior cerebral artery, internal carotid artery and anterior choroidal artery. The internal capsule's vascular supply varied, with the medial lenticulostriate arteries (MLA) and lateral lenticulostriate arteries (LLA) being the primary arteries. The anterior limb was most often supplied by the MLA, while the LLA and anterior choroidal artery dominated the genu and posterior limb. The recurrent artery of Heubner originated mostly from the A2 segment. The distance from the ICA bifurcation to the origin of the first LLA on M1 is 9.55 ± 2.32 mm, and to the first MLA on A1 is 5.35 ± 1.84 mm. MLA branching from A1 and proximal A2 ranged from 5 to 9, while LLA originating from the MCA ranged from 7 to 12. CONCLUSION: This study provides comprehensive understanding of the arterial supply to the internal capsule by combining white matter dissection. The insights gained from this study can help surgeons plan and execute procedures including oncological, psychosurgical, and vascular more accurately and safely. The illustrations derived from the dissections serve as valuable educational material for young neurosurgeons and other medical professionals.

Bilateral Anterior Capsulotomy for Treatment-Resistant Obsessive-Compulsive Disorder.

INTRODUCTION: Ablative surgery is an intervention of last resort for treatment-resistant obsessive-compulsive disorder (TROCD). Our center has been using bilateral anterior capsulotomy (BAC) for the past 20 years for patients eligible for limbic surgery. This report details our experience with BAC for TROCD. METHOD: Five patients with OCD met eligibility criteria for BAC. Entry protocols were complex and took around 6 months to complete. Stereotactic radiofrequency was used to produce the capsulotomies. Lesion length varied between 5.7 and 16.9 mm in the coronal plane. Patients were followed between 4 and 20 years. RESULTS: All 5 patients (100%) were responders as defined by the widely accepted criteria of a reduction of ≥35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) score at 18-month follow-up. Four patients remained responders at the 48 months. One patient was lost to follow-up. Responder status when viewed from the perspective of the YBOCS was sustained over the 4- to 20-year follow-up with one relapse 19 years postsurgery when medications were discontinued. Real-world psychiatric outcomes were different as other vulnerabilities surfaced illustrating the multifactorial determinants of mental health. No patient had any significant long-term neurocognitive or physical side effects. CONCLUSION: BAC should remain an option of last resort for patients with severe OCD who remain unresponsive to all other interventions.

Management and Treatment of Obsessive-Compulsive Disorder (OCD): A Literature Review.

Obsessive-compulsive disorder (OCD) is a prevalent and debilitating mental health condition. This literature review examines the latest strategies in managing and treating OCD, with an emphasis on psychotherapy, pharmacological interventions, and neurosurgical options. A comprehensive literature search utilizing PubMed, Google Scholar, ClinicalKey, and Embase databases was conducted. Utilizing chosen keywords, the resulting articles were filtered based on inclusion and exclusion criteria. Included articles were used to discuss current research regarding OCD treatment and management. Findings reveal the efficacy and obstacles of treatments such as cognitive-behavioral therapy, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and evidence-based neurosurgical methods, offering a broad perspective on OCD management. We discuss the limitations of these established treatments and examine the innovative response of neurosurgery in treating patients with OCD. This review highlights the importance of individualized treatment plans and areas for future research.

Surgery for Obsessive-Compulsive Disorder and Transient Tremors as Newly Reported Side Effect: First Psychiatric Neurosurgery in Egypt.

Introduction: The use of surgery for treatment of psychiatric conditions is a well-established strategy, especially in severe and resistant obsessive-compulsive disorder. Attractive anatomical and functional targets for stereotactic surgery are reported in some studies. Surgery for treatment of psychiatric conditions in our nation and Arab world is obscured and hidden because of several social and cultural limitations, which should be overcome. We report here the first psychiatric neurosurgery in our nation and how we overcome such community limitation. This the first report of postoperative tremor. Case Presentation: Young patient presented with severe and persistent obsessive-compulsive disorder resistant to all non-surgical modalities for several years. Stereotactic ablation surgery was done under local anaesthesia. Marked improvement in our obsessive-compulsive disorder patient after psychiatric neurosurgery with self-limited tremor was not reported before in the literature. The medications were the same before and immediate after surgery and this is not a drug-induced tremor. Postoperative YBOCS showed 90% of improvement. Conclusion: Surgery-induced tremor could be a self-limited side effect after surgery in obsessive-compulsive disorder. Safety and efficacy should be promoted in our nation and Arab world. Society and cultural limitations should be overcome by further research studies, intervention, and activism in the field of mental health systems in our nation and Arab countries to improve awareness.

Neuroablative Intervention for Refractory Obsessive-Compulsive Disorder.

OBJECTIVE: This review aims to investigate the progression of neuroablation, along with documented clinical efficacy and safety, in the management of treatment-resistant obsessive-compulsive disorder (OCD). METHODS: We searched and compiled clinical research results of neuroablation therapy reported to date. We extracted outcomes related to clinical efficacy, side effects, and surgical complications. Additionally, we summarized key claims and findings. RESULTS: Neuroablative intervention is a potential treatment approach for refractory OCD. Recent advancements, such as real-time magnetic resonance monitoring and minimally invasive techniques employing ultrasound and laser, offer distinct advantages in terms of safety and comparative efficacy when compared to conventional methods. However, the absence of randomized controlled trials and long-term outcome data underscores the need for cautious consideration when selecting neuroablation. CONCLUSION: Neuroablative intervention shows promise for refractory OCD, but vigilant consideration is essential in both patient selection and surgical method choices due to the potential for rare yet serious complications.

Innovative perspectives in limbic surgery using deep brain stimulation.

Limbic surgery is one of the most attractive and retaken fields of functional neurosurgery in the last two decades. Psychiatric surgery emerged from the incipient work of Moniz and Lima lesioning the prefrontal cortex in agitated patients. Since the onset of stereotactic and functional neurosurgery with Spiegel and Wycis, the treatment of mental diseases gave attention to refractory illnesses mainly with the use of thalamotomies. Neurosis and some psychotic symptoms were treated by them. Several indications when lesioning the brain were included: obsessive-compulsive disorder, depression, and aggressiveness among others with a diversity of targets. The indiscriminately use of anatomical sites without enough scientific evidence, and uncertainly defined criteria for selecting patients merged with a deficiency in ethical aspects, brought a lack of procedures for a long time: only select clinics allowed this surgery around the world from 1950 to the 1990s. In 1999, Nuttin et al. began a new chapter in limbic surgery with the use of Deep Brain Stimulation, based on the experience of pain, Parkinson's disease, and epilepsy. The efforts were focused on different targets to treat depression and obsessive-compulsive disorders. Nevertheless, other diseases were added to use neuromodulation. The goal of this article is to show the new opportunities to treat neuropsychiatric diseases.

Personalized Definition of Surgical Targets in Major Depression and Obsessive-Compulsive Disorder: A Potential Role for Low-Intensity Focused Ultrasound?

Major Depressive Disorder (MDD) and Obsessive-Compulsive Disorder (OCD) are common and potentially incapacitating conditions. Even when recognized and adequately treated, in over a third of patients with these conditions the response to first-line pharmacological and psychotherapeutic measures is not satisfactory. After more assertive measures including pharmacological augmentation (and in the case of depression, transcranial magnetic stimulation, electroconvulsive therapy, or treatment with ketamine or esketamine), a significant number of individuals remain severely symptomatic. In these persons, different ablation and deep-brain stimulation (DBS) psychosurgical techniques have been employed. However, apart from the cost and potential morbidity associated with surgery, on average only about half of patients show adequate response, which limits the widespread application of these potentially life-saving interventions. Possible reasons are considered for the wide variation in outcomes across different series of patients with MDD or OCD exposed to ablative or DBS psychosurgery, including interindividual anatomical and etiological variability. Low-intensity focused ultrasound (LIFU) is an emerging technique that holds promise in its ability to achieve anatomically circumscribed, noninvasive, and reversible neuromodulation of deep brain structures. A possible role for LIFU in the personalized presurgical definition of neuromodulation targets in the individual patient is discussed, including a proposed roadmap for clinical trials addressed at testing whether this technique can help to improve psychosurgical outcomes.

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.

Neurosurgery for psychiatric disorders: reviewing the past and charting the future.

Surgical techniques targeting behavioral disorders date back thousands of years. In this review, the authors discuss the history of neurosurgery for psychiatric disorders, starting with trephination in the Stone Age, progressing through the fraught practice of prefrontal lobotomy, and ending with modern neurosurgical techniques for treating psychiatric conditions, including ablative procedures, conventional deep brain stimulation, and closed-loop neurostimulation. Despite a tumultuous past, psychiatric neurosurgery is on the cusp of becoming a transformative therapy for patients with psychiatric dysfunction, with an ever-increasing evidence base suggesting reproducible and ethical therapeutic benefit.

Microsurgical anatomy of the anterior cerebral artery and the arterial supply of the cingulate gyrus.

PURPOSE: The cingulate gyrus is a potential surgical area to treat tumours, psychiatric diseases, intractable pain and vascular malformations. The aim of the study was to define the topographic anatomy and arterial supply of the cingulate gyrus located on the medial surface of the cerebral hemisphere. METHODS: We studied thirty-six hemispheres, each hemisected in the midsagittal plane. The vertical thickness of the cingulate gyrus was measured at the anterior commissure (AC), posterior commissure (PC), and genu levels of the corpus callosum. The branches of the anterior and posterior cerebral arteries supplying each zone were noted separately. The arterial pathways were transformed to digital data in AutoCAD to identify the condensation and reduction areas. RESULTS: The mean AC-PC distance was 27.17 ± 1.63 mm. The thinnest region was the genu level of the corpus callosum (10.29 mm). The superior internal parietal artery (SIPA), inferior internal parietal artery (IIPA) and pericallosal artery (PrCA) supplied all zones of the cingulate gyrus. The anterior zone received the greatest supply. The arterial condensation and reduction areas on both sides of cingulate gyrus and its x, y, and z coordinates specified. CONCLUSIONS: The target cingulotomy (TC) area was determined for anterior cingulotomy. The properties of the TC area are that the thinnest region of the cingulate gyrus is supplied relatively less than other areas and is close to the anterior cingulotomy areas in the literature. The arterial reduction area (ARA) was found to be suitable for corpus callosotomy in terms of avoiding haemorrhage.

José Manuel Rodríguez Delgado, Walter Freeman, and Psychosurgery: A Study in Contrasts.

History has conflated the legacies of José Manuel Rodríguez Delgado and Walter Freeman, midcentury proponents of somatic therapies for neuropsychiatric conditions. Both gained notoriety: Delgado after he appeared on the front page of the New York Times having used his stimoceiver to stop a charging bull in Spain; Freeman as the proponent of lobotomy. Both were the object of critique by the antipsychiatry movement and those who felt that their methods and objectives posed a threat to personal liberty. Using archival sources, we demonstrate that this conflation is a misrepresentation of the historical record and that their methods, objectives, ethics, and philosophical commitments differed widely. Accurate knowledge about historical antecedents is a predicate for ethical analysis and becomes especially relevant information as neuroscience develops circuit-based treatments for conditions such as Parkinson disease, depression, and brain injury. Part of that corrective is to counter the conflation of Delgado's and Freeman's life and work. Appreciating their distinctive legacies can help guide neuropsychiatric research done today that might yet haunt future generations.

The Initial Epoch of Psychosurgery in India: A Retrospective Data Review from Mysore Government Mental Hospital.

Background: In the early 20th century, psychosurgery had gained worldwide popularity for treating mentally ill persons, especially in western countries. We attempt to chronicle its journey in the Mysore Government Mental Hospital (MGMH), now the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. Methods: Archived case records and registers of patients admitted from 1939 to 1947 were reviewed to identify those who had undergone psychosurgery. Case records of the identified patients were assessed for clinical information, including the details of psychosurgery. Results: Among the patients, 107 had undergone psychosurgery, primarily leucotomy. Schizophrenia (51.5%) was the most common diagnosis in them, and 33.7% of all patients were reported to have improved. Yet, inconsistencies were found about the presence and degree of improvement. Possible side effects were not consistently documented. Conclusion: Psychosurgery was adopted at the MGMH very soon following its introduction in the western world. However, ambiguity about its benefits and risks was noted in the current study.

Connectivity in deep brain stimulation for self-injurious behavior: multiple targets for a common network?

Self-injurious behavior (SIB) is associated with diverse psychiatric conditions. Sometimes (e.g., in patients with autism spectrum disorder or acquired brain injuries), SIB is the most dominant symptom, severely restricting the psychosocial functioning and quality of life of the patients and inhibiting appropriate patient care. In severe cases, it can lead to permanent physical injuries or even death. Primary therapy consists of medical treatment and if implementable, behavioral therapy. For patients with severe SIB refractory to conventional therapy, neuromodulation can be considered as a last recourse. In scientific literature, several successful lesioning and deep brain stimulation targets have been described that can indicate a common underlying neuronal pathway. The objectives of this study were to evaluate the short- and long-term clinical outcome of patients with severe, therapy refractory SIB who underwent DBS with diverse underlying psychiatric disorders and to correlate these outcomes with the activated connectivity networks. We retrospectively analyzed 10 patients with SIB who underwent DBS surgery with diverse psychiatric conditions including autism spectrum disorder, organic personality disorder after hypoxic or traumatic brain injury or Tourette syndrome. DBS targets were chosen according to the underlying disorder, patients were either stimulated in the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus or ventrolateral thalamus. Clinical outcome was measured 6 months after surgery and at long-term follow-up after 10 or more years using the Early Rehabilitation Barthel index (ERBI) and time of restraint. Connectivity patterns were analyzed using normative connectome. Based on previous literature the orbitofrontal cortex, superior frontal gyrus, the anterior cingulate cortex, the amygdala and the hippocampus were chosen as regions of interest. This analysis showed a significant improvement in the functionality of the patients with DBS in the short- and long-term follow-up. Good clinical outcome correlated with higher connectivity to the amygdala and hippocampus. These findings may suggest a common pathway, which can be relevant when planning a surgical procedure in patients with SIB.

Ethics in psychosurgery.

Ethical problems of psychosurgery are debated since 1970s. The issues of informed consent, political and commercial abuses, lacking evidence and needed regulation are overviewed. New surgical techniques provoke new discussions on goals and limits of psychosurgery.

The Evolution of Modern Ablative Surgery for the Treatment of Obsessive-Compulsive and Major Depression Disorders.

In this review, we describe the evolution of modern ablative surgery for intractable psychiatric disease, from the original image-guided cingulotomy procedure described by Ballantine, to the current bilateral anterior cingulotomy using MRI-guided stereotactic techniques. Extension of the single lesion bilateral cingulotomy to the extended bilateral cingulotomy and subsequent staged limbic leucotomy (LL) is also discussed. Other ablative surgeries for psychiatric disease including subcaudate tractotomy (SCT) and anterior capsulotomy (AC) using modern MRI-guided ablative techniques, as well as radiosurgical capsulotomy, are described. Finally, the potential emerging role of MR-guided focused ultrasound (MRgFUS) for treating conditions such as major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) is discussed.

A comparative history of psychosurgery.

The term "psychosurgery" reflecting neurosurgical treatment of mental disorders, was coined by a Portuguese neurologist Egas Moniz (1874-1955), who, in 1935, suggested a procedure named prefrontal leucotomy (or lobotomy) aimed to divide white matter tracts connecting prefrontal cortex and thalamus. Starting from 1936, this technique and its subsequent modification (transorbital lobotomy) was zealously promoted by a neurologist Walter Freeman (1895-1972) and a neurosurgeon James Watts (1904-1994) at George Washington University, who in 1942 summarized their experience in a monograph, which publication resulted in a tremendous worldwide interest in psychosurgical interventions. The present review describes comparative development of prefrontal leucotomy followed by stereotactic ablation and neurostimulation in three different geographical regions: USA, USSR/Russia, and Far East (China and Japan), where psychosurgery followed nearly similar courses, progressing from the initial enthusiasm and high clinical caseloads to nearly complete disregard. The opposition to neurosurgical interventions for mental disorders around the world was led by different groups and for varying reasons, but, unfortunately, always with political considerations mixed in. Today, with vast advancements in neuroimaging, stereotactic neurosurgical techniques, and physiological knowledge, psychiatric neurosurgery can be performed with much greater precision and safety.

Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

BACKGROUND: Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS: Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS: Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION: These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

Commentary on the Continued Investigational Status of DBS for Psychiatric Indications.

Behavioral disorders exact a tragic toll on patients, families, and society. Consequently, the search for better treatments is a public health priority. Recent research promises to lead to advances in psychiatric treatment that may include implantation of deep brain stimulation (DBS) devices. In this commentary, the authors discuss how promising results from initial pilot studies of DBS in treatment-resistant depression (TRD) were not validated in 2 randomized, controlled, multicenter trials. Reliance on pilot data may have contributed to the selection of primary efficacy endpoints that were not achieved, and to the underestimation of adverse events and device-related complications. Published data on the population prevalence of affective disorders also may have led sponsors to overestimate the number of patients with TRD who were candidates for DBS therapy. Consequently, a more complete discussion of certain aspects of the depression trials may allow a realistic appraisal of the clinical and ethical situation of DBS therapy for TRD in a US regulatory context. A US regulatory perspective also may clarify the clinical research and reimbursement consequences of the Humanitarian Device Exemption (HDE) approval status of DBS for obsessive-compulsive disorder (OCD). Retrospective analyses akin to failure modes and effects analysis in engineering may clarify unexpected results in the DBS depression trials. Recent research suggests that subject selection in future trials may be augmented by advanced neuroimaging methods. For the present, the noncommercial research status of DBS to treat depression and the HDE status for OCD appear likely to remain in place.

Behavioral disorders.

Making lesions in the brain to relieve the distress of mental illness has had a checkered career due to a mixture of misuse and also caution about making permanent lesions in the brain where there was no physical abnormality. However, over the last 10 years a more flexible approach has developed. The method is still in its infancy and very little used. However, GKNS has been shown to be useful for OCD and also some cases of sever anxiety. It has been attempted for depression and anorexia nervosa but at present its role for these conditions remains to be determined.