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: 10210305
• 负责人: Wayne K Goodman
• 金额: $ 152.14万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210305
• 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.

对于顽固性强迫症 (OCD) 患者，腹侧纹状体 (VS) 深部脑刺激 (DBS) 可有效减轻约 60% 病例的症状严重程度，但仍有改善的空间。 既具有临床益处，又能减少 DBS 引起的行为副作用，尤其是轻躁狂。 因素可能是未能适应性地调整 DBS 以应对消极和积极的阶段性变化 配价状态（即，分别与强迫症相关的痛苦和轻躁狂）。 (aDBS) 系统可以记录、刺激和使用来自大脑的信号来对大脑做出响应性调整 具体目标 1 是训练设备对 OCD 的急性波动进行准确分类。 相关的痛苦和轻躁狂的出现，并将这些状态与其他情感状态区分开来 不需要调整刺激措施。 具体目标 2 是制定能够适应的控制政策。 自动调整刺激参数来调节这些不良状态。 强迫症相关的痛苦加剧需要增加刺激（更高的振幅或更宽的脉冲宽度） 而轻躁狂将对减少的刺激做出反应。这些目标将通过两阶段来实现。 对 10 名患有顽固性强迫症的成年人进行 aDBS 的早期可行性研究将进入为期 6 个月的开放式试验。 标记双侧 aDBS，随后进行 2 个月的辅助认知行为治疗 (CBT)。 将进入为期 4 周的盲法停药期，以评估持续 DBS 的需要。在第一阶段，5 名受试者将进入。 按照 FDA 人体器械豁免 (HDE) 批准的 VS DBS 治疗强迫症的程序进行手术。 将使用每个患者的“精确映射”来优化和个性化电极植入 DBS 编程会话中的高场纤维束成像的解剖学连接也将实现。 用于训练算法对不同价态进行分类，例如症状激发范例。 在这种范式中，会引发不同程度的可控制的与强迫症相关的困扰。 将捕获锁定的生理和行为数据来构建分类器：局部场电位（LFP） 来自 VS、头皮脑电图和自动面部表情识别 (AFAR)，客观地测量 我们追求使用组合 LFP/EEG 数据的分类器比 VS 表现更好。 仅 LFP，但需要直接皮层记录来准确分类和创建完整的 嵌入式、独立的 aDBS 系统 在第二阶段，5 名受试者将接受 VS DBS 手术以及双侧 DBS 手术。 将皮质电图 (ECoG) 记录导线硬膜下放置在前额叶目标处，通过静息告知 第一阶段的状态功能 MRI 和术前扫描将基于 VS 和建立新的分类器。 ECoG LFP 和自适应刺激算法在转移到门诊环境之前在诊所进行了测试。 满足所有研究里程碑将产生一个原型流动 aDBS 系统，该系统可以管理 自动控制强迫症症状和设备相关副作用的波动。