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: 10586133
• 负责人: Casey Harrison Halpern
• 金额: $ 40.63万
• 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/10586133
• 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; Diagnostic; 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; Participant; Pattern; Physiological; Physiology; Psychiatry; Recurrence; Research Personnel; Resolution; Role; Safety; Satiation; Series; Serious Adverse Event; Signal Transduction; Source; Specificity; Sum; System; Time; Ventral Lateral Thalamic Nucleus; Weight Gain; Work; bariatric surgery; behavioral response; cohort; craving; data archive; feasibility trial; food craving; human subject; implantation; improved; insight; interest; loss of control over eating; neural; neuroimaging; pre-clinical; preclinical study; primary endpoint; response; 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.

项目摘要/摘要 暴饮暴食是最常见的饮食失调障碍，最多可使美国成年人中有10％。它的特征是 通过反复出现的发作，以失去控制感，饮食中的大笔款项。临床前研究已经实施 伏隔核（NAC）失去控制饮食的失调。提供更深入的理解 对于NAC如何构成人类饮食的基础，我们利用了来自早期可行性试验的数据 反应性神经刺激损失控制饮食（NCT03868670）。这项UH3研究旨在检查 NAC饮食中NAC的响应性神经刺激的安全性，可行性和初步效率。二 当前，受试者已入学，并成功接受了双边手术植入。 NAC中的神经刺激系统（Neuropace，Inc。）。这两个主题都在响应迅速的DBS指导下 由NAC Delta（2-4Hz）振荡（即“ Delta-Responsive DBS”），并且较少的LOC（主要端点）。 在FDA审查中，招募4个主题的补充。在这里，我们打算表征角色 人类饮食行为中的NAC三角洲信号传导。初步数据表明腹侧NAC Delta功率 在预期和类似Loc的渴望状态下，双边连通性提升，特有可口食品。 在Delta响应DBS之后，Fullermore，Delta功率和腹侧双侧NAC连接降低了 并且这种效果对刺激参数优化敏感。我们的中心假设表明NAC 作为LOC饮食中的关键区域，以及异常的三角洲信号传导是LOC饮食的基础。因此，我们预测 Delta响应DBS通过拯救NAC异常的三角洲信号传导对LOC行为作用。我们的目标 确定NAC三角洲的功率和连通性如何将LOC饮食与正常饮食区分开， 确定对NAC Delta反应性DBS的行为反应的神经基础。因为LOC是所有人共同的 binges，是许多精神健康障碍的经诊断特征，这项工作将提供无价 与许多精神病学有关的洞察力。