Combined Cortical and Subcortical Recording and Stimulation as a Circuit-Oriented Treatment for Obsessive-Compulsive Disorder

皮层和皮层下记录与刺激相结合作为强迫症的电路导向治疗

• 批准号: 9358443
• 负责人: DARIN D DOUGHERTY
• 金额: $ 61.06万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 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 2023-12-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9358443
• 关键词: Address; Affect; Animal Model; Anxiety; Area; Automobile Driving; Behavior; Behavior Disorders; Belief; Bilateral; Biological Markers; Brain; Chronic; Clinical; Clinical Trials; Corpus striatum structure; Coupled; Data; Deep Brain Stimulation; Disease; Electric Stimulation; Electrodes; Electroencephalography; Elements; Event; Event-Related Potentials; Extinction (Psychology); Feedback; Flare; Frequencies; Fright; Functional Magnetic Resonance Imaging; Goals; Gold; Grooming; Habits; Hand functions; Human; Implanted Electrodes; Interruption; Intervention; Lead; Learning; Lesion; Link; Macaca; Mediating; Mental Depression; Mental disorders; Modeling; Monitor; Motivation; Motor; Neurobiology; Neurosciences; Neurosurgeon; Obsession; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Outcome; Pathologic; Patients; Pharmaceutical Preparations; Phase; Procedures; Protocols documentation; Psychiatrist; Psychophysics; Research Domain Criteria; Research Personnel; Resistance; Rest; Rewards; Rodent; Safety; Severities; Signal Transduction; Site; Surface; Symptoms; Syndrome; System; Systems Theory; Testing; Thinking; Time; Ventral Striatum; Work; base; blind; brain electrical activity; capsule; caudate nucleus; compulsion; conditioned fear; design; dynamic system; experience; improved; neuroimaging; neurosurgery; new technology; novel therapeutics; potential biomarker; response; safety and feasibility; severe mental illness; simulation; symptomatic improvement; theories; therapy development; treatment response; trial design

Project Abstract This project is a pilot clinical trial of a new brain stimulation treatment for obsessive-compulsive disorder. OCD is a mental illness that affects 4-7 million people in the US. Of those, 50-70% still have substantial symptoms after being treated with medication or talk therapy. Recently, clinicians have started trying to treat OCD with deep brain stimulation (DBS). DBS involves surgically placing electrodes into the brain, then sending electrical stimulation currents through those electrodes. Most investigators think that DBS for OCD works by affecting brain circuits called the cortico-striato-thalamo-cortical loops, or CSTC loops. The belief is that OCD is caused by the CSTC loops being too strongly connected, so that signals get "stuck" in them and become the stuck, perseverative, obsessional thinking of OCD. To interrupt these loops, investigators have placed DBS into the ventral capsule/ventral striatum (VC/VS), the "S" of CSTC. VC/VS DBS has helped several patient who had very treatment-resistant OCD. However, about half do not get better. We hypothesize that this is because DBS does not always influence cortico-striatal loops correctly, because it only affects a single area in this multi-area circuit. Our main objective (Aim 1) is to test a stimulator that affects the deep brain and the cortex (brain surface) at once and tries to break the abnormal CSTC synchrony. It drives two brain areas at slightly different frequencies, keeping them "out of sync". Our second objective is to test whether activity in the CSTC loop correlates to the symptoms of OCD. No study has proven that these two are linked in humans, because it is difficult to record from the human brain, especially over long periods of time and from deep brain areas. We will use a novel technology, the Medtronic PC+S "sensing DBS", to record the brain's activity while delivering the stimulation treatment (Aim 2a). As patients' symptoms improve, we expect to see that connectivity and synchrony between the surface and deep brain decreases along the same trajectory. We will also capture recordings during symptom flares and as patients participate in symptom-triggering activities such as exposure therapy sessions. This will help us further determine how well this brain activity correlates to symptoms. Finally, to help capture clearer signals, we will also collect those recordings while patients do a fear task that is linked to OCD severity, using EEG to further understand the cortico-striatal response to DBS (Aim 2b). This study leverages a broad interdisciplinary team of psychiatrists, statisticians, a neurosurgeon, and electrophysiologists, all with experience in OCD and brain stimulation.

项目摘要 该项目是一项新的脑刺激治疗强迫症的试点临床试验。OCD 这是一种精神疾病，在美国影响着400万到700万人。其中，50-70%仍然有实质性的症状 在接受药物治疗或谈话治疗后。最近，临床医生已经开始尝试用 脑深部电刺激（DBS）DBS是通过手术将电极植入大脑， 刺激电流通过这些电极。大多数研究者认为DBS治疗强迫症是通过影响 大脑回路称为皮质-纹状体-丘脑-皮质回路，或CSTC回路。强迫症是由 由于CSTC环路连接得太强，因此信号被“卡住”并被卡住， 强迫症的顽固性思维为了中断这些循环，研究人员将DBS置于 腹侧囊/腹侧纹状体（VC/VS），CSTC的“S”型。 VC/VS DBS已经帮助了一些患有非常难治性强迫症的患者。然而，大约一半的人没有得到 好多了我们假设这是因为DBS并不总是正确地影响皮质-纹状体回路， 因为它只影响这个多区域电路中的单个区域。我们的主要目标（目标1）是测试刺激器 它同时影响大脑深部和皮层（大脑表面），并试图打破异常的CSTC。 同步性它以略微不同的频率驱动两个大脑区域，使它们“不同步”。我们的第二 目的是测试CSTC环的活动是否与强迫症的症状相关。没有研究证明 这两者在人类中是联系在一起的，因为很难从人脑中记录下来，特别是长时间的记录， 时间和大脑深层区域。我们将使用一种新的技术，美敦力PC+S“传感 DBS”，用于在提供刺激治疗时记录大脑活动（目标2a）。因为病人的症状 我们预计，大脑表层和深层之间连接性和同步性会降低 沿着相同的轨迹。我们还将在症状发作期间以及患者参与 暴露疗法等引发焦虑的活动。这将帮助我们进一步确定 这种大脑活动与症状相关最后，为了帮助捕捉更清晰的信号，我们还将收集 记录，而患者做恐惧任务，这是与强迫症的严重程度，使用脑电图，以进一步了解 皮质-纹状体对DBS的反应（目标2b）。这项研究利用了一个广泛的跨学科精神科医生团队， 统计学家、神经外科医生和电生理学家，他们都有强迫症和脑刺激方面的经验。