Investigating the role of nucleus accumbens delta signaling in loss of control

研究伏隔核δ信号在失控中的作用

• 批准号: 10426696
• 负责人: Casey Harrison Halpern
• 金额: $ 39.34万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-07 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426696
• 关键词: Adult; Anatomy; Animals; BRAIN initiative; Behavior Control; Behavioral; Bilateral; Binge eating disorder; Corpus striatum structure; Cues; Data; Data Set; Deep Brain Stimulation; Detection; Devices; Dorsal; Eating; Eating Behavior; Eating Disorders; Electrodes; Enrollment; Exhibits; Food; Frequencies; Graph; Home; Human; Hunger; Implant; Left; Mediating; Mental disorders; Methods; Mus; Neuroanatomy; Nucleus Accumbens; Operative Surgical Procedures; Outcome; Palate; Participant; Pattern; Physiological; Physiology; Psychiatry; Research Personnel; Resolution; Role; Satiation; Series; Serious Adverse Event; Signal Transduction; Source; Specificity; Sum; System; Time; Weight; Work; bariatric surgery; behavioral response; cohort; craving; data archive; feasibility trial; food craving; human subject; implantation; improved; insight; interest; loss of control over eating; neuroimaging; pre-clinical; preclinical study; primary endpoint; relating to nervous system; response; safety and feasibility; spatiotemporal; tool

Project Summary/Abstract Binge eating disorder is the most common eating disorder afflicting up to 10% of US adults. It is characterized by recurring episodes of eating large sums with a sense of loss of control. Preclinical studies have implicated dysregulation of the nucleus accumbens (NAc) in loss of control eating. To provide a deeper understanding as to how the NAc underlies LOC eating in humans, we leverage data from an early feasibility trial entitled Responsive Neurostimulation for Loss of Control Eating (NCT03868670). This UH3 study aims to examine the safety, feasibility, and preliminary efficacy of responsive neurostimulation of the NAc for LOC eating. Two subjects are currently enrolled and successfully underwent bilateral surgical implantation of the responsive neurostimulation system (NeuroPace, Inc.) into the NAc. Both subjects are undergoing responsive DBS guided by NAc delta (2-4Hz) oscillations (i.e. “delta-responsive DBS”) and have exhibited less LOC (primary endpoint). A supplement to enroll the 4 additional subjects is under FDA review. Here, we intend to characterize the role of NAc delta signaling in human LOC eating behaviors. Preliminary data suggests that ventral NAc delta power and bilateral connectivity elevate during anticipatory and LOC-like cravings states, specific to palatable foods. Futhermore, delta power and ventral bilateral NAc connectivity are reduced following delta-responsive DBS, and that this effect is sensitive to stimulation parameter optimization. Our central hypothesis suggests the NAc as a key region in LOC eating, and that aberrant delta signaling underlies LOC eating. As such, we predict that delta-responsive DBS acts on LOC behaviors through a rescue of the NAc’s aberrant delta signaling. Our aims are to determine how NAc delta power and connectivity can differentiate LOC eating from normal eating, and identify neural underpinnings of behavioral response to NAc delta-responsive DBS. As LOC is common to all binges and is a transdiagnostic feature of many mental health disorders, this work will provide invaluable insight relevant to much of Psychiatry.

项目概要/摘要 暴食症是最常见的饮食失调症，影响多达 10% 的美国成年人。它的特点是 反复出现大量进食并伴有失控感。临床前研究表明 伏隔核（NAc）失调导致饮食失控。为了提供更深入的理解 为了了解 NAc 如何成为人类 LOC 饮食的基础，我们利用了一项早期可行性试验的数据，该试验题为 响应性神经刺激治疗饮食失控 (NCT03868670)。这项 UH3 研究旨在检验 NAc 反应性神经刺激用于 LOC 进食的安全性、可行性和初步疗效。二 受试者目前已入组并成功进行了反应性双侧手术植入 神经刺激系统（NeuroPace, Inc.）进入 NAc。两个受试者都在接受 DBS 引导的响应式治疗 通过 NAc delta (2-4Hz) 振荡（即“delta 响应 DBS”），并且表现出较少的 LOC（主要终点）。 招募另外 4 名受试者的补充正在接受 FDA 审查。在这里，我们想描述一下这个角色 人类 LOC 饮食行为中的 NAc δ 信号传导。初步数据表明，腹侧 NAc δ 功率 在预期和类似 LOC 的渴望状态（特定于可口食物）期间，双边连通性会增强。 此外，在 Delta 响应 DBS 后，Delta 功率和腹侧双边 NAc 连接性会减少， 并且这种效应对刺激参数优化敏感。我们的中心假设表明 NAc 作为 LOC 进食的关键区域，异常的 Delta 信号是 LOC 进食的基础。因此，我们预测 Delta 响应 DBS 通过拯救 NAc 的异常 Delta 信号来作用于 LOC 行为。我们的目标 确定 NAc delta 功率和连接如何区分 LOC 饮食和正常饮食，以及 确定 NAc δ 反应性 DBS 行为反应的神经基础。由于 LOC 对所有人来说都是通用的 暴饮暴食是许多精神健康疾病的跨诊断特征，这项工作将提供无价的价值 与许多精神病学相关的见解。