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: 10399402
• 负责人: DARIN D DOUGHERTY
• 金额: $ 53.88万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399402
• 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; Data; Deep Brain Stimulation; Disease; Electric Stimulation; Electrodes; Electroencephalography; Elements; Event; Event-Related Potentials; Extinction; Feedback; Flare; Frequencies; Fright; Functional Magnetic Resonance Imaging; Goals; 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; Patient Participation; Patients; Persons; 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; biomarker identification; blind; brain electrical activity; capsule; caudate nucleus; compulsion; conditioned fear; design; dynamic system; experience; improved; neuroimaging; neurosurgery; new technology; novel therapeutics; pilot test; 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