Adaptive DBS in Non-Motor Neuropsychiatric Disorders: Regulating Limbic Circuit Imbalance

非运动神经精神疾病的适应性 DBS：调节边缘回路不平衡

• 批准号: 10451827
• 负责人: Wayne K Goodman
• 金额: $ 154.43万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10451827
• 关键词: Acute; Adult; Affect; Affective; Algorithms; Anatomy; Anxiety; Architecture; Behavior; Behavioral; Bilateral; Biological Markers; Blinded; Brain; Classification; Clinic; Clinical; Cognitive Therapy; Computers; Data; Deep Brain Stimulation; Devices; Distress; Electric Stimulation; Electrodes; Electroencephalography; Emotional; Exposure to; Face; Failure; Feasibility Studies; Feedback; Functional Magnetic Resonance Imaging; Funding; Generations; Home; Human; Implant; Investigation; Label; Measures; Mental disorders; Meta-Analysis; Moods; Negative Valence; Neurosurgical Procedures; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Outcome; Pacemakers; Patient Selection; Patient Self-Report; Patients; Pattern; Phase; Physiologic pulse; Physiological; Policies; Positive Valence; Procedures; Regulation; Research; Resistance; Rest; Risk; Safety; Scalp structure; Scanning; Severities; Signal Transduction; Site; Stream; Symptoms; System; Technology; Telemetry; Testing; Therapeutic; Time; Training; Ventral Striatum; Width; algorithm training; base; biosignature; design; feasibility testing; hypomania; implantation; individual patient; meetings; neural circuit; neuropsychiatric disorder; neurosurgery; open label; phase change; prototype; reduce symptoms; response; side effect; symptom management; symptomatic improvement; tool; tractography

In patients with intractable Obsessive-Compulsive Disorder (OCD), ventral striatum (VS) deep brain stimulation (DBS) effectively reduces symptom severity in about 60% of cases. However, there is room for improvement in both clinical benefits and reduction of DBS-induced behavioral side effects, especially hypomania. A critical factor may be failure to adaptively adjust DBS in response to phasic changes in negatively and positively valenced states (i.e., OCD-related distress and hypomania, respectively). New generation adaptive DBS (aDBS) systems can record, stimulate and use signals from the brain to make responsive adjustments to the patient's behavioral state. Specific Aim 1 is to train the device to accurately classify acute fluctuations in OCD- related distress and emergence of hypomania and distinguish these states from other affective states that do not require adjustments in stimulation. Specific Aim 2 is to develop adaptive control policies that can automatically adjust stimulation parameters to regulate these undesired states. It is hypothesized that exacerbations in OCD-related distress will require increased stimulation (higher amplitude or wider pulse width) whereas hypomania will respond to decreased stimulation. These aims will be executed using a two-phase Early Feasibility Study of aDBS in 10 adults with intractable OCD. Subjects will enter a 6-month trial of open- label bilateral aDBS followed by 2 months of adjunctive cognitive behavioral therapy (CBT). Subsequently, they will enter a 4-week blinded discontinuation period to assess need for ongoing DBS. In Phase I, 5 subjects will have surgery as per procedures of the FDA Human Device Exemption (HDE) approval for VS DBS in OCD. Electrode implantation will be optimized and personalized using “precision mapping” of each patient's anatomical connectivity from high-field tractography in native space. DBS programming sessions will also serve to train the algorithms to classify different valence states. For example, a symptom provocation paradigm will elicit different levels of manageable OCD-related distress. During this paradigm multiple streams of time- locked physiological and behavioral data will be captured to build a classifier: Local Field Potentials (LFPs) from the VS, Scalp EEG, and Automated Facial Affect Recognition (AFAR), which objectively measures emotional valence. We hypothesize that classifiers using combined LFP/EEG data will perform better than VS LFPs alone, but that direct cortical recordings will be needed for accurate classification and creation of a fully embedded, self-contained, aDBS system. In Phase II, 5 subjects will have VS DBS surgery along with bilateral subdural placement of electrocorticographic (ECoG) recording leads at a prefrontal target, informed by resting state functional MRI from Phase I and pre-operative scans. New classifiers will be built based on VS and ECoG LFPs and adaptive stimulation algorithms tested in the clinic before transfer to the ambulatory setting. Meeting all study milestones would result in a prototype ambulatory aDBS system that would manage fluctuations in OCD symptoms and device-related side effects automatically.

在具有顽固性强迫症（OCD）的患者中，腹侧纹状体（VS）深脑刺激 （DBS）在约60％的病例中有效地降低了症状严重程度。但是，还有改进的余地 临床益处和DBS诱导的行为副作用的降低，尤其是躁狂症。批判 因素可能是由于响应负面和积极的阶段变化而无法自适应调整DBS 价值状态（即分别与OCD相关的困扰和躁狂症）。新一代自适应DB （ADB）系统可以记录，刺激和使用来自大脑的信号，以进行响应的调整 患者的行为状态。具体目标1是训练设备以准确地对OCD-中的急性波动进行分类。 相关的困扰和躁狂症的出现，并将这些国家与其他受影响的国家区分开 不需要调整刺激。具体目标2是制定自适应控制政策 自动调整刺激参数以调节这些不希望的状态。假设 与OCD相关的困扰中加重将需要增加刺激（更高的放大器或更宽的脉冲宽度） 而躁狂症会对刺激减少的反应。这些目标将使用两阶段执行 10名顽固性强迫症成年人的ADB的早期可行性研究。受试者将进入6个月的开放式试验 - 标签双边ADB，然后进行2个月的辅助认知行为疗法（CBT）。随后，他们 将进入一个为期4周的盲目中断期，以评估持续的DBS的需求。在第一阶段，将有5个受试者 根据FDA人体设备豁免程序（HDE）批准对OCD中的VS DBS进行手术。 电极植入将通过每个患者的“精确映射”进行优化和个性化 来自天然空间中高场拖拉机的解剖连通性。 DBS编程会议也将 用于训练算法以对不同的价状态进行分类。例如，症状挑衅范式 将引起不同级别的可管理性强迫症相关的困扰。在此范式中，多个时间流 - 锁定的物理和行为数据将被捕获以构建分类器：本地字段电位（LFPS） 从VS，头皮脑电图和自动化面部情感识别（AFAR）中 情绪价值。我们假设使用合并的LFP/EEG数据的分类器比VS更好 单独使用LFP，但是需要直接的皮质记录才能准确分类和创建 嵌入式，独立的ADBS系统。在第二阶段，有5名受试者将进行VS DBS手术以及双边 电气图（ECOG）记录潜在客户的皮肤下部放置在前额叶目标处，并通过休息来告知 I阶段和术前扫描的状态功能MRI。新分类器将根据VS和 ECOG LFP和自适应刺激算法在转移到门诊环境之前在诊所测试。 满足所有学习里程碑将导致原型的门诊ADB系统，该系统将管理 强迫症症状和设备相关的副作用的波动自动自动。

项目成果

Continued access to investigational brain implants.

• DOI: 10.1038/s41583-018-0004-5
• 发表时间: 2018-06
• 期刊: Nature reviews. Neuroscience
• 作者: Lázaro-Muñoz G;Yoshor D;Beauchamp MS;Goodman WK;McGuire AL
• 通讯作者: McGuire AL

Automated Detection of Enhanced DBS Device Settings.

• DOI: 10.1145/3395035.3425354
• 发表时间: 2020-10
• 期刊: Companion Publication of the 2020 International Conference on Multimodal Interaction
• 作者: Ding Y;Ertugrul IO;Darzi A;Provenza N;Jeni LA;Borton D;Goodman W;Cohn J
• 通讯作者: Cohn J

Decoding task engagement from distributed network electrophysiology in humans.

从人类分布式网络电生理学中解码任务参与度。

• DOI: 10.1088/1741-2552/ab2c58
• 发表时间: 2019
• 期刊: Journal of neural engineering
• 影响因子: 4
• 作者: Provenza,NicoleR;Paulk,AngeliqueC;Peled,Noam;Restrepo,MariaI;Cash,SydneyS;Dougherty,DarinD;Eskandar,EmadN;Borton,DavidA;Widge,AlikS
• 通讯作者: Widge,AlikS

Treatment Search Fatigue and Informed Consent.

• DOI: 10.1080/21507740.2020.1866115
• 发表时间: 2021-01
• 期刊: AJOB neuroscience
• 作者: Zuk P;Lázaro-Muñoz G
• 通讯作者: Lázaro-Muñoz G

Brain Imaging in Psychiatry: Time to Move From Regions of Interest and Interpretive Analyses to Connectomes and Predictive Modeling?

精神病学中的脑成像：是时候从感兴趣区域和解释性分析转向连接组和预测建模了？

• DOI: 10.1176/appi.ajp.20220907
• 发表时间: 2023
• 期刊: The American journal of psychiatry
• 作者: Abdallah,ChadiG;Sheth,SameerA;Storch,EricA;Goodman,WayneK
• 通讯作者: Goodman,WayneK