Utilizing changes in human brain connectivity to establish a dose-response relationship involved in the therapeutic actions of prefrontal brain stimulation on depression symptoms

利用人脑连接的变化建立剂量反应关系，参与前额叶脑刺激对抑郁症状的治疗作用

• 批准号: 10560493
• 负责人: Nolan R. Williams
• 金额: $ 49.09万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560493
• 关键词: Acceleration; Anterior; Attenuated; Behavior; Behavioral; Brain; Clinical; Cognitive; Data; Development; Devices; Diagnosis; Disease remission; Dose; Ethics; FDA approved; Functional Magnetic Resonance Imaging; Future; Goals; Hour; Human; Individual; Intelligence; Learning; Left; Link; Magnetic Resonance Imaging; Major Depressive Disorder; Measurable; Measurement; Measures; Mental Depression; Methodology; Modification; Moods; Motor; Motor Evoked Potentials; Nature; Neurobiology; Neurosciences; Participant; Pathologic; Patients; Pattern; Phase; Physiologic pulse; Prefrontal Cortex; Regulatory Element; Remission Induction; Remission Induction Therapy; Resistance; Rest; Risk; Symptoms; System; Techniques; Technology; Therapeutic; Treatment Effectiveness; attenuation; cingulate cortex; clinical effect; depressive symptoms; disability; disease heterogeneity; effective therapy; emotion regulation; experimental study; functional MRI scan; healthy volunteer; improved; innovation; neural circuit; neural network; neuropsychiatry; neuroregulation; novel; open label; reduce symptoms; repetitive transcranial magnetic stimulation; response; response biomarker; side effect; tool; treatment-resistant depression

ABSTRACT Major depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited in part by insufficient understanding of the mechanism of disease remission. In turn, efforts to elucidate mechanisms have been challenging due to disease heterogeneity and limited effectiveness of treatments, which require weeks-to-months to induce remission. In this application, we propose to focus on applying a novel neurostimulation strategy to participants with TRD. We recently developed a form of repetitive transcranial magnetic stimulation that induces remission in 90% of individuals with severe, treatment resistant MDD in 1-5 days which we called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). This methodology provides a new tool to begin exploring the network-level mechanisms of MDD remission. Following SAINT, fc significantly decreases default mode network (DMN)-subgenual cingulate cortex (sgACC) which is correlated with change in clinical scales. In this application, we propose to target the L-DLPFC-sgACC target with active (n=50) versus sham (n=50) SAINT and determine if active SAINT (Aim 1) attenuates sgACC-DMN connectivity and (Aim 2) significantly reduces symptoms of depression. Decreases in fc may underlie reductions in depression; thus, we will relate reductions in these potential moderators to identify the best symptom targets. Completion of this proposal will further establish a safe, effective, and non-invasive device-based treatment for TRD along with the iterative neural circuitry changes at each daily dose of stimulation that summate to produce the clinical effect.

抽象的 重度抑郁症（MDD）很普遍且令人衰弱，改进治疗的发展受到限制 部分原因是对疾病缓解机制的理解不足。反过来，努力阐明 机制由于疾病异质性和治疗有效性有限而具有挑战性，这 需要几周到月才能诱发缓解。在此应用程序中，我们建议专注于应用小说 TRD参与者的神经刺激策略。我们最近开发了一种重复的经颅的形式 磁刺激在1-5中诱导90％的严重，耐药MDD的个体中诱导缓解 我们称之为斯坦福大学的天数加速了智能神经调节疗法（SAINT）。这种方法 提供了一种新工具，可以开始探索MDD缓解的网络级机制。跟随圣人，足球俱乐部 显着降低默认模式网络（DMN）-subgenual Catigulatual Cortex（SGACC） 随临床量表的变化。在此应用程序中，我们建议用Active靶向L-DLPFC-SGACC目标 （n = 50）与假（n = 50）圣人，并确定活跃的圣人（aim 1）是否减弱sgacc-dmn连接性 （AIM 2）显着减少抑郁症状。 FC的减少可能是降低的基础 沮丧;因此，我们将关联这些潜在的主持人的减少，以确定最佳症状靶标。 该提案的完成将进一步建立安全，有效且非侵入性设备的治疗方法 TRD以及迭代的神经回路在每日刺激的每日剂量上都会发生变化，这些刺激总结为产生 临床效果。