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 暴饮暴食障碍是最常见的饮食障碍，困扰着高达10%的美国成年人。它的特点是 通过反复出现吃大笔钱的情况，感到失控。临床前研究表明 控制进食失控的伏隔核(NAC)调节失调。以提供更深入的理解，如 关于NAC是如何在人类中食用低碳水化合物的，我们利用了来自早期可行性试验的数据，名为 失控饮食的反应性神经刺激(NCT03868670)。这项UH3研究旨在检查 NAC反应性神经刺激用于低脂饮食的安全性、可行性和初步疗效。二 受试者目前入选，并成功地接受了双侧手术植入的响应性 神经刺激系统(NeuroPace，Inc.)送进了南汽。两名受试者都在接受响应性DBS指导 NAC增量(2-4赫兹)振荡(即“增量响应型DBS”)，并表现出较少的LOC(主要终点)。 纳入这4个额外科目的补充材料正在接受FDA的审查。在这里，我们打算描述这个角色的特征 NAC Delta信号在人类进食LOC行为中的作用。初步数据表明，腹侧NAC三角洲电力 在预期的和类似LOC的渴望状态下，双边连接性会提升，尤其是在美味的食物上。 此外，三角洲反应性DBS后，Delta功率和腹侧NAC连接性降低， 这种效应对刺激参数的优化很敏感。我们的中心假设是NAC 作为进食LOC的关键区域，而这种异常的Delta信号是进食LOC的基础。因此，我们预测 Delta响应型DBS通过拯救NAC异常的Delta信号来作用于LOC行为。我们的目标 是确定NAC Delta电源和连接如何将LOC饮食与正常饮食区分开来，以及 确定NAC Delta-Responsitive DBS行为反应的神经基础。因为LOC对所有人来说都是常见的 狂欢是许多精神健康障碍的跨诊断特征，这项工作将提供无价的 与大部分精神病学相关的洞察力。