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

项目摘要 该项目是一种治疗强迫症的新的脑刺激疗法的试点临床试验。强迫症 是一种精神疾病，在美国有400-700万人受到影响。在这些人中，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，临床医生开始尝试用药物治疗强迫症。 脑深部刺激(DBS)。DBS涉及到通过外科手术将电极放入大脑，然后向大脑发送电流 刺激电流通过这些电极。大多数研究人员认为DBS治疗强迫症的作用是通过影响 大脑回路被称为皮质-纹状体-丘脑-皮质环，或CSTC环。人们认为强迫症是由 由于CSTC环路连接得太强，以至于信号在环路中“卡住”，成为卡住的， 坚持不懈，痴迷于强迫症的思维。为了中断这些循环，调查人员将星展银行放入 腹囊/腹侧纹状体(VC/VS)，中国科协的“S”。 VC/VS DBS已经帮助了几位非常难治的强迫症患者。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-纹状体环， 因为它只影响这个多区域电路中的一个区域。我们的主要目标(目标1)是测试刺激器 这会同时影响大脑深层和皮质(大脑表面)，并试图打破异常的CSTC 同步性。它以略有不同的频率驱动两个大脑区域，使它们保持“不同步”。我们的第二个 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 这两者在人类身上是联系在一起的，因为很难从人脑中记录下来，特别是很长时间 一段时间和大脑深处的区域。我们将使用一项新技术，美敦力PC+S DBS“，在实施刺激治疗时记录大脑活动(目标2a)。作为患者的症状 改善后，我们希望看到表层和深层大脑之间的连通性和同步性降低 沿着同样的轨迹。我们还将在症状发作期间和患者参与 引发症状的活动，如暴露治疗课程。这将有助于我们进一步确定 这种大脑活动与症状相关。最后，为了帮助捕获更清晰的信号，我们还将收集 在患者进行与强迫症严重程度相关的恐惧任务时进行录音，使用脑电进一步了解 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病学家团队， 统计学家、神经外科医生和电生理学家，都有强迫症和脑刺激方面的经验。

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.