Targeted modulation of symptom-specific brain circuits with transcranial magnetic stimulation

通过颅磁刺激有针对性地调节症状特异性脑回路

• 批准号: 10369674
• 负责人: MICHAEL D FOX
• 金额: $ 22.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369674
• 关键词: Address; Anxiety; Beck depression inventory; Biological Markers; Brain; Clinical; Clinical Trials; Data; Dorsal; Equipment and supply inventories; FDA approved; Functional Magnetic Resonance Imaging; Goals; Individual Differences; Lateral; Left; Location; MRI Scans; Magnetic Resonance Imaging; Major Depressive Disorder; Mental Depression; Mental disorders; Outcome; Paper; Participant; Patients; Pattern; Prefrontal Cortex; Psychiatry; Randomized; Rest; Sample Size; Scanning; Site; Symptoms; Testing; Transcranial magnetic stimulation; Work; base; cohort; depressive symptoms; design; functional MRI scan; improved; insight; neuroimaging marker; neuroregulation; patient subsets; prospective; symptom cluster; targeted biomarker; targeted treatment; treatment-resistant depression

Project summary Transcranial magnetic stimulation (TMS) is an FDA-approved therapy for treatment-resistant depression, but clinical outcomes vary. We recently showed that TMS outcomes may be optimized by targeting different circuits to treat different symptoms (Siddiqi et al, Am J Psychiatry 2020). Among patients who received clinical TMS to the left dorsal lateral prefrontal cortex for depression, improvement in “dysphoric” symptoms was associated with TMS to one brain circuit, while improvement in “anxiosomatic” symptoms was associated with TMS to a different brain circuit. However, this study was unable to investigate biomarkers and mechanisms of targeting various brain circuits. Using resting-state fMRI data in a subset of this cohort, we have now generated preliminary data showing that treatment-induced connectivity change within each circuit can be used as a biomarker of which circuit was stimulated and which symptom clusters improved. Further, individualized connectivity between the patient’s TMS site and each of these circuits covaried with TMS-induced connectivity changes, suggesting a potential mechanism. However, these preliminary results are limited by small sample size with a retrospective design that relies on incidental variance in the TMS site rather than targeted stimulation of these two brain circuits. In the current project, we will prospectively target TMS in order to clearly assess its target-specific effects on functional connectivity. In Aim 1, we will test whether our prospective targeting of our two circuits will induce selective connectivity changes within those circuits. In Aim 2, we will test whether the magnitude of these connectivity changes can be predicted by the strength of the TMS site’s individualized connectivity to the underlying circuit. Together, this work will establish whether resting-state fMRI can act as a reliable biomarker of target engagement when seeking to modulate specific brain circuits in patients. Further, it will lend insight into potential mechanisms of previously observed symptom-specific neuromodulation effects. This work is a critical step towards mechanistically-driven clinical trials focused on symptom-specific and circuit-specific neuromodulation in depression, with the long-term goal of personalized and transdiagnostic circuit-targeted therapy for mental illness more generally.

项目摘要 经颅磁刺激（TMS）是FDA批准的治疗耐药性疗法，但 临床结果各不相同。我们最近表明，TMS结果可以通过靶向不同的 治疗不同症状的电路（Siddiqi等，Am J Psychiatry 2020）。在接受临床的患者中 左侧背侧前额叶前额叶皮层抑郁症，“烦躁不安”符号的改善是 与TMS与一个大脑电路相关，而“抗焦虑”符号的改进与 TMS到不同的大脑电路。但是，这项研究无法研究生物标志物和机制 针对各种大脑电路。 在该队列的一个子集中使用静止状态fMRI数据，我们现在生成了初步数据 治疗引起的每个电路内的连通性变化可以用作哪个电路的生物标志物 刺激并改善了哪些症状簇。此外，患者的个性化连通性 TMS位点和这些电路中的每个电路都与TMS诱导的连接性变化协变，表明潜力 机制。但是，这些初步结果受到小样本量的限制，并具有回顾性设计 这取决于TMS位点的偶然方差，而不是针对这两个大脑电路的靶向刺激。在 当前的项目，我们可能会针对TMS，以便清楚地评估其针对目标的影响 功能连接。 在AIM 1中，我们将测试我们对两个电路的预期定位是否会引起选择性连通性 这些电路中的变化。在AIM 2中，我们将测试这些连接性的幅度是否可以变化 可以通过TMS位点与基础电路的个性化连接性的强度进行预测。一起， 这项工作将确定静止状态fMRI是否可以作为目标参与的可靠生物标志物 试图调节患者的特定脑电路。此外，它将借入潜在的机制 先前观察到的症状特异性神经调节作用。这项工作是迈向的关键一步 机械驱动的临床试验集中于症状特异性和电路特异性神经调节 抑郁症，具有个性化和经诊断电路的长期目标 疾病更普遍。