Targeting DBS Therapy to the OCD Network Using fMRI and Intracranial Recordings

使用功能磁共振成像和颅内记录针对强迫症网络进行 DBS 治疗

• 批准号: 10671069
• 负责人: Andrew Moses Lee
• 金额: $ 20.19万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10671069
• 关键词: Adverse effects; Anterior; Anxiety; Attenuated; Bilateral; Biological Markers; Brain; Chronic; Cognitive; Cognitive Therapy; Complex; Corpus striatum structure; Deep Brain Stimulation; Development; Devices; Diffusion Magnetic Resonance Imaging; Distant; Distress; Electric Stimulation; Electrophysiology (science); FDA approved; Functional Magnetic Resonance Imaging; Functional disorder; Image; Impairment; Implant; Implanted Electrodes; Individual; Internal Capsule; Limb structure; Magnetic Resonance Imaging; Manic; Maps; Measures; Mediating; Medical; Mental Depression; Mental disorders; Methods; Modeling; Obsessive-Compulsive Disorder; Outcome; Patients; Pattern; Pharmaceutical Preparations; Pilot Projects; Prefrontal Cortex; Process; Protocols documentation; Refractory; Reporting; Sleep disturbances; Stimulus; Structure; Structure of terminal stria nuclei of preoptic region; Symptoms; System; Technology; Therapeutic; Therapeutic Effect; Thinking; Tissues; Transcranial magnetic stimulation; Ventral Striatum; cingulate cortex; cingulotomy; cohort; disability; imaging study; improved; improved outcome; neural circuit; neural network; neurophysiology; neuroregulation; novel; off-label use; precision medicine; psychiatric symptom; repetitive behavior; response; therapeutic target; white matter; young adult

PROJECT SUMMARY/ABSTRACT According to the WHO, OCD is one of the top ten causes of disability among young adults, and one in ten patients have severe symptoms refractory to cognitive and medical therapies. OCD is thought to be mediated by a cortico-striato-thalamo-cortical (CSTC) circuit anchored in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). Deep brain stimulation (DBS) is a targeted circuit-based treatment that has been used to treat severe, refractory cases of OCD. However, DBS remains limited in its use because: 1) currently only 50- 60% of patients respond to therapy, 2) DBS programming is a complex, trial-and-error process that can take months to years to optimize, and 3) DBS is associated with adverse effects such as sleep disturbance and mania. We aim to overcomes these limitations by developing methods to target DBS therapy to the neural circuits underlying OCD. Developments in DBS technology now allow for MR imaging to be performed while DBS is On/Off and local field potential recordings can now be acquired from DBS leads, providing a unique opportunity to determine whether DBS therapy is functionally engaging the intended OCD circuitry. Here, we propose to: 1) Develop protocols for generating personalized spatial activation maps using stimulation-based fMRI, and 2) Identify individualized electrophysiological biomarkers of OCD and related psychiatric symptoms responsive to DBS using intracranial recordings. Together, these imaging and electrophysiological methods can be used to verify that DBS is engaging the OCD network. In our pilot studies, we demonstrate the feasibility of generating stimulation maps using fMRI protocols in a single subject, finding activation in the OFC and ACC distant from the empirically determine therapeutic contacts. We also describe the identification of a gamma biomarker of depression within the bed nucleus of the stria terminalis (BNST), serving as a proof-of-concept that it is possible to identify electrophysiological biomarkers of psychiatric symptoms. We currently have FDA investigational device exemption (IDE) approval to implant DBS leads in the OFC and ACC in addition to the standard anterior limb of the internal capsule (ALIC) DBS target for OCD. This proposal seeks to determine whether our initial imaging findings will hold in a larger cohort of subjects and to determine the feasibility of discovering novel OCD biomarkers by performing intracranial recordings across critical nodes of the OCD network. These studies provide a path towards personalized, circuit-based precision medicine to improve DBS for OCD.

项目摘要/摘要 根据世卫组织的说法，强迫症是年轻人中残疾的十大原因之一，十分之一 患者对认知和医疗疗法的症状严重症状。强迫症被认为是介导的 通过固定在前扣带回皮层（ACC）和 眶额皮质（OFC）。深脑刺激（DBS）是一种基于靶向电路的治疗 治疗严重的强迫症的难治性病例。但是，DBS的使用仍然有限，因为：1）目前只有50-- 60％的患者对治疗的反应，2）DBS编程是一个复杂的试验过程，可以接受 优化的几个月到几年，3）DBS与不良反应（例如睡眠障碍和躁狂症）有关。 我们的目标是通过开发针对DBS治疗的方法来克服这些局限性 基础强迫症。 DBS技术的发展现在允许在DBS时执行MR成像 现在可以从DBS线索中获取开/关和本地现场潜在录音，从而提供了独特的机会 确定DBS治疗是否在功能上与预期的OCD电路相关。在这里，我们建议：1） 开发使用基于刺激的fMRI生成个性化空间激活图的协议，2） 确定反对反应的强迫症和相关精神症状的个性化电生理生物标志物 DBS使用颅内记录。这些成像和电生理方法共同用于 验证DBS是否参与OCD网络。 在我们的试点研究中，我们证明了使用fMRI方案在单个中生成刺激图的可行性 受试者，在OFC和ACC远离经验中确定治疗触点的激活。我们 还描述了在质子末端的床核内抑制抑郁症的伽马生物标志物的鉴定 （BNST），作为概念证明，可以识别精神病的电生理生物标志物 症状。我们目前已对植入物DBS Lead的FDA调查设备豁免（IDE）批准 OFC和ACC除了OCD内胶囊（ALIC）DBS目标的标准前肢（ALIC）。这 提案旨在确定我们最初的成像发现是否会在较大的主题中成立和 通过在跨颅内记录中发现新型OCD生物标志物的可行性 OCD网络的关键节点。这些研究为基于个性化的，基于电路的精度提供了途径 改善强迫症的DBS的药物。