Halpern, Casey H.

Background Psychiatric disorders are increasingly contributing to global disability. Despite advances in conservative management, the prevalence of treatment-resistant cases remains high. Meanwhile, neurosurgery for psychiatric disorders (NPD) remains underused, largely due to strict regulations and historical concerns, particularly those related to neuropsychological side effects (NPSE). Objective To address this issue, we conducted a systematic review with meta-analysis to compare NPSE associated with radiofrequency ablative NPD to those observed in neuro-oncological, neurovascular and epilepsy surgeries. Methods PubMed, Embase and LILACS databases were searched in April 2024 for articles published in English/Spanish from 1990 to 2022, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results A total of 48 articles with 2678 participants were included. The frequency of transient and permanent NPSE in the NPD group ranged from 0.94% to 11.50% and 0.94% to 2.03%, respectively, comparable to the other surgical groups (epilepsy: 0.31–11.70%; vascular: 0.52–22.90%; oncology: 0.94–17.60% for transient NPSE; epilepsy: 0.31–12%; vascular: 0.40–1.96% and oncology: 0.84–1.48% for permanent NPSE). Regarding permanent NPSE, arguably the most critical consideration, the NPD group showed better outcomes in memory, language and social cognition than the epilepsy group, but worse outcomes in executive and perceptual-motor functions. Compared with the vascular group, the NPD group had better executive function but worse complex attention. Finally, the NPD group had fewer permanent deficits than the oncology group in executive function, complex attention and perceptual-motor domains, although language performance was lower. Conclusions Contemporary NPD apparently carries a similar risk of NPSE as other conventional neurosurgical procedures, challenging misconceptions and this unjustified barrier to its broader use.

Abstract Objectives Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)‐guided depth leads to provide responsive stimulation to neocortical gray matter. Methods Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti‐responders (≤0%) based on percent seizure reduction at 1 year post‐implant (1‐Y). Pre‐operative T1‐weighted magnetic resonance imaging and post‐operative computed tomography images were merged, and the Euclidean distance between the sEEG epileptic focus (sEEG‐EF) and the nearest RNS System depth lead contacts was calculated. Results A total of 87 depth leads were implanted in 55 patients across neocortical brain regions. The median reduction in clinical seizures improved from 66.7% at 1‐Y to 77.5% at long‐term follow‐up (LTFU: 2.35 ± 0.95 years), with 10 patients (18.2%) achieving complete seizure freedom. Seven patients (12.7%) experienced six serious adverse events. At 1‐Y, shorter Euclidean distance between the sEEG‐EF and RNS System depth leads predicted improved seizure outcome in strong responders ( β = −0.84, p = 0.008) but not in weak responders ( β = 0.21, p = 0.9) or anti‐responders ( β = −20.34, p = 0.11). At LTFU, there was no significant relationship between Euclidean distance and seizure reduction in strong responders ( β = 0.77, p = 0.18), weak responders ( β = 2.05, p = 0.54), or anti‐responders ( β = 0.24, p = 0.99). Exploratory analyses at 1‐Y showed nominal associations between older age ( ρ = 0.32), longer epilepsy duration ( ρ = 0.27), and non‐mesial temporal sEEG‐EFs and greater seizure reduction; however, none survived Bonferroni correction (adjusted α = 0.0027; all post‐correction p > 0.0027), and no associations were observed at LTFU. Significance In this series, neocortical depth leads for RNS therapy had favorable safety and efficacy and proximity to the sEEG‐EF drove initial outcomes for strong responders to RNS therapy. Plain Language Summary In this multi‐center study, patients with difficult‐to‐treat seizures received brain‐responsive stimulation using a device called responsive neurostimulation (RNS), which delivers small electrical pulses to reduce seizures. We focused on patients treated with electrodes placed in the brain's outer regions (the neocortex) and guided by a mapping procedure called sEEG. On average, patients had their seizures cut by two‐thirds after one year and by more than three‐quarters with longer follow‐up, with about one in five becoming seizure‐free. The treatment was safe, and closer electrode placement to the seizure source helped explain early—but not long‐term—improvements.

BACKGROUND AND OBJECTIVES: Stereotactic procedures are used to manage a diverse set of patients across a variety of clinical contexts. The stereotactic devices and software used in these procedures vary between surgeons, but the fundamental principles that constitute safe and accurate execution do not. The aim of this work is to describe these principles to equip readers with a generalizable knowledge base to execute and understand stereotactic procedures. METHODS: A combination of a review of the literature and empirical experience from several experienced surgeons led to the creation of this work. Thus, this work is descriptive and qualitative by nature, and the literature is used to support instead of generate the ideas of this framework. RESULTS: The principles detailed in this work are categorized based on 5 clinical domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. Illustrations and tables are used throughout to convey the concepts in an efficient manner. CONCLUSION: Stereotactic procedures are complex, requiring a thorough understanding of each step of the workflow. The concepts described in this work enable functional neurosurgeons with the fundamental knowledge necessary to provide optimal patient care.

BACKGROUND AND OBJECTIVES: Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS: We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS: We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION: This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.

Abstract Only recently has the rodent hippocampus been implicated in orexigenic appetitive processing1,2. This function has been found to be mediated at least in part by lateral hypothalamic inputs involving an orexigenic neuropeptide, melanin-concentrating hormone3. This circuit remains elusive in humans. Here, we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues and this modulation was specific to the dorsolateral hippocampus. Lastly, structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behavior revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

Microelectrode recordings were performed during awake deep brain stimulation surgery for obsessive-compulsive disorder, revealing robust brain oscillations that were plainly visible throughout the ventral striatum. There was an elegant topological correspondence between each oscillation and the underlying brain anatomy, most prominently a ~35-Hz gamma-oscillation specific to the nucleus accumbens. Direct provocation of the patient’s contamination obsession modulated both firing rate and gamma-oscillation amplitude within the nucleus accumbens. NEW & NOTEWORTHY Surgical implantation of deep brain stimulating electrodes (DBS) to treat obsessive-compulsive disorder (OCD) is an option for patients who have not fully responded to medical intervention or cognitive behavioral therapy. We measured the electrophysiology of a collection of deep brain structures during awake DBS surgery for an OCD patient with an obsession about cleanliness and contamination. The anatomic delineation of these deep brain structures was revealed by distinct brain rhythms, most notably a ~35 Hz oscillation specific to the nucleus accumbens. In the first ever measurement of a human obsessive thought, we found that this ~35-Hz biomarker, as well as the local neuronal action potential rate, were modulated by handing the patient a toothbrush to bring to his face and instructing him to “imagine brushing your teeth with this dirty toothbrush.”