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: 10509975
• 负责人: Andrew Moses Lee
• 金额: $ 24.23万
• 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/10509975
• 关键词: Adverse effects; Anterior; Anxiety; Attenuated; Bilateral; Biological Markers; Brain; Chronic; Cognitive; Cognitive Therapy; Complex; Deep Brain Stimulation; Development; Devices; Diffusion Magnetic Resonance Imaging; Distant; Distress; Electric Stimulation; Electrophysiology (science); Ensure; FDA approved; Functional Magnetic Resonance Imaging; Functional disorder; Image; Impairment; Implant; Implanted Electrodes; Individual; Internal Capsule; Investigation; 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; base; 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.

项目概要/摘要 据世界卫生组织称，强迫症是导致年轻人残疾的十大原因之一，并且十分之一的人患有强迫症。 患者有认知和药物治疗难治的严重症状。强迫症被认为是可以调节的 由锚定于前扣带皮层 (ACC) 的皮质-纹状体-丘脑-皮质 (CSTC) 回路和 眶额皮质（OFC）。深部脑刺激 (DBS) 是一种基于靶向回路的治疗方法，已被用于 治疗严重的、难治性的强迫症病例。然而，DBS 的使用仍然受到限制，因为：1) 目前只有 50- 60% 的患者对治疗有反应，2) DBS 编程是一个复杂的试错过程，可能需要 需要数月至数年的时间来优化，3) DBS 与睡眠障碍和躁狂等不良反应有关。 我们的目标是通过开发针对神经回路的 DBS 治疗方法来克服这些限制 潜在的强迫症。 DBS 技术的发展现在允许在 DBS 进行的同时进行 MR 成像。 现在可以从 DBS 领导处获取开/关和本地现场电位记录，从而提供了独特的机会 确定 DBS 疗法是否在功能上参与预期的强迫症回路。在此，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，以及 2) 识别强迫症和相关精神症状的个体化电生理生物标志物 DBS 使用颅内记录。这些成像和电生理学方法一起可用于 验证 DBS 是否正在使用 OCD 网络。 在我们的试点研究中，我们证明了使用 fMRI 协议在单个 受试者发现 OFC 和 ACC 中的激活远离凭经验确定的治疗接触。我们 还描述了终纹床核内抑郁症伽马生物标志物的鉴定 （BNST），作为一个概念验证，可以识别精神疾病的电生理生物标志物 症状。目前，我们已获得 FDA 试验器械豁免 (IDE) 批准，可将 DBS 导线植入 OFC 和 ACC 以及用于 OCD 的标准内囊前肢 (ALIC) DBS 目标。这 该提案旨在确定我们最初的影像学发现是否适用于更大的受试者群体，并 确定通过跨颅内记录发现新的强迫症生物标志物的可行性 OCD 网络的关键节点。这些研究提供了一条通往个性化、基于电路的精度的道路 改善强迫症 DBS 的药物。