Cortical-limbic circuit dynamics of approach-avoidance conflict in humans

Nature Communications · 2026-03-12

Choosing to approach or avoid is common in everyday life and excessive avoidance is a cardinal feature of anxiety disorders. We use intracranial EEG to define a prefrontal-limbic circuit supporting approach and avoidance. Presurgical epilepsy patients (n = 20) performed an approach-avoidance conflict decision-making task inspired by the arcade game Pac-Man, where patients trade off rewards against losses from ghost attack. During approach, theta power increases across a limbic circuit including the hippocampus, amygdala, orbitofrontal cortex and anterior cingulate cortex, which drops during avoidance. Theta connectivity between this circuit and lateral prefrontal cortex increases during approach and falls during avoidance. Network connectivity tracks how long patients approach, with enhanced synchronicity extending approach times. During imminent threat, the system switches to sustained increase in high-frequency activity in the lateral prefrontal cortex. The results provide evidence of a distributed prefrontal-limbic circuit, mediated by theta oscillations and high frequency activity, underlying approach-avoidance conflict in humans.

Safety of 3 Tesla MRI in active peripheral nerve field stimulation device for facial pain

Stereotactic and Functional Neurosurgery · 2026-04-07

INTRODUCTION: Peripheral nerve field stimulation (PNFS) for facial pain delivers subcutaneous electrical stimulation to reduce pain. Functional MRI (fMRI) can be used to characterize central effects of neuromodulation techniques such as deep brain stimulation (DBS) and spinal cord stimulation (SCS). However, the safety and utility of MRI in patients with PNFS has not been established, limiting both clinical MRI use and the application of fMRI in this population. This study evaluated the MRI safety and feasibility of imaging an active SCS implant used for PNFS in patients with facial pain; and defined sequence parameters for concurrent blood-oxygenation-level-dependent (BOLD) fMRI acquisition. METHODS: An anthropomorphic 3D-printed phantom filled with tissue-mimicking gel and fitted with an SCS implant replicating a patient with PNFS was used for in vitro safety testing. Two phantom experiments evaluated the relationship between (i) head specific absorption rate (SAR), (ii) time-averaged positive radiofrequency magnetic field component (B1+rms), and maximal temperature rises at critical locations (i.e., distal lead electrodes, cranial coiling, and implantable pulse generator) across clinical and research-based structural and fMRI sequences. For validation, a PNFS patient was scanned using localizer, T1-weighted Magnetization-Prepared Rapid Gradient Echo (T1w MPRAGE), and BOLD fMRI sequences informed by phantom experiments. RESULTS: FMRI during active PNFS is safe under specific conditions, with temperature increases remaining below the 2°C threshold at all monitored locations. Heating had a stronger relationship with head SAR (higher adjusted coefficient of determination (𝑅2) value) than B1+rms, particularly at distal lead electrodes. These in vitro findings informed selection of safe fMRI protocols for in vivo scanning. A patient (n=1) underwent MRI with no device- or patient-related adverse events. Successful fMRI acquisition was achieved, demonstrating engagement of pain-related regions in the patient. CONCLUSION: Phantom testing confirmed the safety and feasibility of MRI with an active SCS device configured for facial PNFS. These findings, specific to the tested conditions, underscore the need for context-specific safety evaluations to enable safe MRI in such implantable medical devices.

Roles of alternative polyadenylation in psychiatric disorder risk

Genomic psychiatry : · 2024-07-18 · 2 citations

Alternative polyadenylation (APA) is a pervasive regulatory mechanism in the human brain that controls the stability and cellular localization of mRNA transcripts. Single-nucleotide polymorphisms associated with psychiatric disorders may exert their deleterious effects by altering 3’ untranslated site usage, which may change the stability and processing of mRNA transcripts. The authors previously performed a 3’APA transcriptomic-wide association study using the DePars2 framework and the GTEx v8, PsychENCODE, and ROS/MAP datasets to identify APA-linked genes associated with eleven brain disorders. Here we focus on 3’APA-linked genes associated with the major psychiatric conditions: schizophrenia, bipolar disorder, and depression. There are 286 APA-linked genes associated with these psychiatric disorders, and 60%–65% of these genes have not been associated with the major psychiatric disorders through their expression and/or splicing. Protein–protein interaction networks indicate that APA-linked genes associated with schizophrenia are involved in intracellular transport and cellular localization pathways. Future research is needed to elucidate the role of alternative 3’ untranslated region usage of APA-linked genes on neuronal function and phenotypic expression in psychiatric disorders.

Postoperative wound care protocol prevents surgical site infection after craniotomy

Infection Control and Hospital Epidemiology · 2024-10-14 · 6 citations

Abstract Background: Postoperative wound care after craniotomy is not standardized. Objective: Evaluate the impact of a standardized post-craniotomy wound care protocol on surgical site infection (SSI). Design and Setting: Prospective quasi-experimental single-center intervention cohort study involving adult patients undergoing craniotomy at a 461-bed academic medical center in Orange County, California from January 2019–March 2023 (intervention) compared to January 2017–December 2018 (baseline). Methods: A postoperative neurosurgical wound care protocol was developed involving chlorhexidine cloths to remove incisional clots and to clean the surgical incision and adjacent hair after craniotomy surgery. Protocol adherence was monitored by routine inpatient surveillance of wounds and photo-documentation for real-time feedback to surgeons and nursing staff. Impact of the intervention was assessed using multivariable regression models. Results: There were 3560 craniotomy surgeries and 62 (1.7%) SSIs; 1251 surgeries and 30 (2.4%) SSIs during baseline, and 2309 surgeries and 32 (1.4%) SSIs during intervention. Process evaluation after implementation found significant decreases in incisional clots, erythema, drainage, and unclean hair. In multivariable analysis, the intervention was associated with fewer SSI (odds ratio (OR): 0.5 (0.3, 0.9), P = 0.02). Conclusions: A standardized post-craniotomy wound care protocol involving cleaning of the incision and adjacent hair, including removal of incisional clots with chlorhexidine cloths was effective in reducing the risk of SSI.

What is the Philosophy of Neurosurgery? Systematic Review and Defining the Discipline

World Neurosurgery · 2024-03-15 · 2 citations

INTRODUCTION: Despite centuries of joint investigation of philosophy and neurological interventions, a founding account for the philosophy of neurosurgery has yet to be rigorously constructed or defended. This paper reviews recent work on the philosophy of neurosurgery, spanning metaphysics, epistemology, and value theory, to establish a framework and clinical relevance for study in the philosophy of neurosurgery. METHODS: A systematic review of an online database was conducted using the broad search terms, "Philosophy AND (Neurosurgery OR Neurological Surgery)." Records were included if they demonstrated relevance to the philosophy of neurosurgery and analytical rigor, but were excluded if solely legal, clinical, or ethical principles were considered without substantive discussion of underlying ethical frameworks and philosophical principles. RESULTS: Of 8025 candidates from online and print records, 16 records (14 from online sources and 2 from an edited volume) met inclusion criteria for the systematic review. Three dealt with metaphysics, 3 dealt with epistemology, 4 dealt with value theory, 5 dealt with metaphysics/epistemology, and 1 dealt with value theory/metaphysics. Questions of free will, consciousness, personal identity, neurosurgical knowledge, ascription of other minds, deontology, and minimalism, among others, were considered. DISCUSSION: Based on identified studies, the philosophy of neurosurgery is defined as the discipline of rigorously and methodically addressing metaphysical, epistemological, and value-theoretic questions arising from physically intervening in the nervous system. We discuss future directions for questions within the philosophy of neurosurgery and consider their relevance for patient care and the practice of neurosurgery.

Neuromodulation and Disorders of Consciousness: Systematic Review and Pathophysiology

Neuromodulation Technology at the Neural Interface · 2024-10-18 · 8 citations

INTRODUCTION: Disorders of consciousness (DoC) represent a range of clinical states, affect hundreds of thousands of people in the United States, and have relatively poor outcomes. With few effective pharmacotherapies, neuromodulation has been investigated as an alternative for treating DoC. To summarize the available evidence, a systematic review of studies using various forms of neuromodulation to treat DoC was conducted. MATERIALS AND METHODS: Adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic literature review, the PubMed, Scopus, and Web of Science databases were queried to identify articles published between 1990 and 2023 in which neuromodulation was used, usually in conjunction with pharmacologic intervention, to treat or reverse DoC in humans and animals. Records were excluded if DoC (eg, unresponsive wakefulness syndrome, minimally conscious state, etc) were not the primary clinical target. RESULTS: A total of 69 studies (58 human, 11 animal) met the inclusion criteria for the systematic review, resulting in over 1000 patients and 150 animals studied in total. Most human studies investigated deep brain stimulation (n = 15), usually of the central thalamus, and transcranial magnetic stimulation (n = 18). Transcranial direct-current stimulation (n = 15) and spinal cord stimulation (n = 6) of the dorsal column also were represented. A few studies investigated low-intensity focused ultrasound (n = 2) and median nerve stimulation (n = 2). Animal studies included primate and murine models, with nine studies involving deep brain stimulation, one using ultrasound, and one using transcranial magnetic stimulation. DISCUSSION: While clinical outcomes were mixed and possibly confounded by natural recovery or pharmacologic interventions, deep brain stimulation appeared to facilitate greater improvements in DoC than other modalities. However, repetitive transcranial magnetic stimulation also demonstrated clinical potential with much lower invasiveness.

Awake ripples enhance emotional memory encoding in the human brain

Nature Communications · 2024-01-03 · 22 citations

Enhanced memory for emotional experiences is hypothesized to depend on amygdala-hippocampal interactions during memory consolidation. Here we show using intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task increased awake ripples after encoding of emotional, compared to neutrally-valenced stimuli. Further, post-encoding ripple-locked stimulus similarity is predictive of later memory discrimination. Ripple-locked stimulus similarity appears earlier in the amygdala than in hippocampus and mutual information analysis confirms amygdala influence on hippocampal activity. Finally, the joint ripple-locked stimulus similarity in the amygdala and hippocampus is predictive of correct memory discrimination. These findings provide electrophysiological evidence that post-encoding ripples enhance memory for emotional events.

Obtaining brain tissue from living patients for psychiatry research: collaboration with patients with epilepsy and neurosurgeons

The Lancet Psychiatry · 2023-04-21

Trends and disparities in deep brain stimulation utilization in the United States: a Nationwide Inpatient Sample analysis from 1993 to 2017

The Lancet Regional Health - Americas · 2023-09-20 · 50 citations

Background: Deep brain stimulation (DBS) is an approved treatment option for Parkinson's Disease (PD), essential tremor (ET), dystonia, obsessive-compulsive disorder and epilepsy in the United States. There are disparities in access to DBS, and clear understanding of the contextual factors driving them is important. Previous studies aimed at understanding these factors have been limited by single indications or small cohort sizes. The aim of this study is to provide an updated and comprehensive analysis of DBS utilization for multiple indications to better understand the factors driving disparities in access. Methods: The United States based National Inpatient Sample (NIS) database was utilized to analyze the surgical volume and trends of procedures based on indication, using relevant ICD codes. Predictors of DBS use were analyzed using a logistic regression model. DBS-implanted patients in each indication were compared based on the patient-, hospital-, and outcome-related variables. Findings: Our analysis of 104,356 DBS discharges from 1993 to 2017 revealed that the most frequent indications for DBS were PD (67%), ET (24%), and dystonia (4%). Although the number of DBS procedures has consistently increased over the years, radiofrequency ablation utilization has significantly decreased to only a few patients per year since 2003. Negative predictors for DBS utilization in PD and ET cohorts included age increase and female sex, while African American status was a negative predictor across all cohorts. Significant differences in patient-, hospital-, and outcome-related variables between DBS indications were also determined. Interpretation: Demographic and socioeconomic-based disparities in DBS use are evident. Although racial disparities are present across all indications, other disparities such as age, sex, wealth, and insurance status are only relevant in certain indications. Funding: This work was supported by Alan & Susan Hudson Cornerstone Chair in Neurosurgery at University Health Network.

Schizophrenia and neurosurgery: systematic review and theories

Neurosurgical FOCUS · 2023-02-01 · 11 citations

OBJECTIVE: Despite its relatively low prevalence, schizophrenia has a high burden of illness due to its lifelong effects and the fact that it is often refractory to psychotropic treatment. This review investigated how neurosurgical interventions, primarily neuromodulation through deep brain stimulation (DBS), can mitigate treatment-refractory schizophrenia. Pathophysiological data and ongoing clinical trials were reviewed to suggest which targets hold promise for neurosurgical efficacy. METHODS: A systematic review of the literature was conducted via an electronic search of the PubMed, Scopus, and Web of Science databases. Included papers were human or animal studies of neurosurgical interventions for schizophrenia conducted between 2012 and 2022. An electronic search of ClinicalTrials.gov and the International Clinical Trials Registry Platform was conducted to find ongoing clinical trials. The ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) assessment tool was used to evaluate risk of bias in the study. RESULTS: Eight human and 2 rat studies were included in the review. Of the human studies, 5 used DBS targeting the nucleus accumbens, subgenual anterior cingulate cortex, habenula, and substantial nigra pars reticulata. The remaining 3 human studies reported the results of subcaudate tractotomies and anterior capsulotomies. The rat studies investigated DBS of the nucleus accumbens and medial prefrontal cortex. Overall, human studies demonstrated long-term reduction in Positive and Negative Syndrome Scale scores in many participants, with a low incidence of surgical and psychological side effects. The rat studies demonstrated improved prepulse and latent inhibition in the targeted areas after DBS. CONCLUSIONS: As identified in this review, recent studies have investigated the potential effects of therapeutic DBS for schizophrenia, with varying results. DBS targets that have been explored include the hippocampus, subgenual anterior cingulate cortex, habenula, substantia nigra pars reticulata, and medial prefrontal cortex. In addition to DBS, other neuromodulatory techniques such as neuroablation have been studied. Current evidence suggests that neuroablation in the subcaudate tract and anterior capsulotomy may be beneficial for some patients. The authors recommend further exploration of neuromodulation for treatment-refractory schizophrenia, under the condition that rigorous standards be upheld when considering surgical candidacy for these treatments, given that their safety and efficacy remain to be determined.