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

项目总结/摘要 暴食症是最常见的饮食失调症，困扰着多达10%的美国成年人。它的特点 因为反复出现大量进食并有失控感。临床前研究表明， 在饮食失控时，丘脑核（NAc）的调节异常。以提供更深入的了解， 为了了解NAc是如何成为人类暴食的基础，我们利用了一项名为 进食失控的反应性神经刺激（NCT 03868670）。这项UH 3研究旨在研究 NAc反应性神经刺激治疗厌食症的安全性、可行性和初步疗效。两 受试者目前已入组，并成功接受了双侧手术植入的反应 神经刺激系统（NeuroPace，Inc.）进入NAC。两名受试者均接受了反应性DBS引导 通过NAc delta（2- 4 Hz）振荡（即“delta-响应DBS”），并且表现出更少的振幅（主要终点）。 正在接受FDA审查，以补充招募4例额外受试者。在这里，我们打算描述的作用， NAc delta信号在人类进食行为中的作用。初步数据表明腹侧NAc δ功率 和双边连接性在预期和LOC样渴望状态期间升高，具体到可口的食物。 在三角洲反应DBS后，future，三角洲功率和腹侧双侧NAc连接减少， 并且该效应对增产参数优化敏感。我们的中心假设是， 作为进食的关键区域，而异常的δ信号是进食的基础。因此，我们预测， δ-反应性DBS通过拯救NAc的异常δ信号传导作用于神经行为。我们的目标 是为了确定NAc delta功率和连接如何区分正常饮食和非正常饮食， 确定对NAc δ-反应性DBS行为反应的神经基础。因为所有人都有 狂欢，是许多精神健康障碍的transdiagnosis特征，这项工作将提供宝贵的 与许多精神病学相关的见解。

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.