Probing the Functional and Behavioral Impact of Precision Circuit Modulation in Neuropsychiatric Disorders

项目摘要/摘要 网络模型越来越多地被用来描述精神疾病的神经生物学基础。 特定回路内的功能障碍会促进特定症状的形成。这意味着一个机会 通过调节特定的电路来治疗特定的症状。重复经颅磁刺激(RTMS) 能够进行特定于电路的神经调节。它也是一种治疗严重抑郁障碍的既定疗法 (MDD)。临床经验表明，rTMS通过刺激不同的症状结构来治疗不同的症状 电路。然而，仍然严重缺乏机械证据来支持假定的网络。 RTMS的机制，限制了其以更个性化和优化的方法治疗患者的能力。 此机械性方案将首先使用静息状态功能连接(FC)MRI和定制分析 用于以高分辨率表征健康和抑郁症患者的功能网络拓扑的管道。 该数据将用于导出在功能上位于离散前额网络中的RTMS目标(例如，控制， 默认、显著、边缘/奖励)。接下来，患者将参加受试者内部的设计，在这个设计中，他们将经历 在不同的日期向每个目标发送rTMS。每个目标在给定的一天将被刺激四次，并且在每一次之后 刺激变化将使用：(1)REST-BOLD MRI(评估FC变化)，(2)任务-BOLD MRI(评估被验证为测试RDoC结构的范例上粗体激活的变化)，(3)基于状态 问卷调查或(4)神经心理测试。这项工作将促进个性化的神经调节 基于网络拓扑学的方法。这将为大规模的临床试验授粉，以评估 差动电路调制。它还将阐明神经精神病学中的电路结构关系 精神错乱。

Project Summary/Abstract Network models are increasingly invoked to characterize the neurobiological underpinnings of mental illnesses. Dysfunction within specific circuits promotes the formation of specific symptoms. This suggests an opportunity to treat specific symptoms by modulating specific circuits. Repetitive transcranial magnetic stimulation (rTMS) is capable of circuit-specific neuromodulation. It is also an established treatment for Major Depressive Disorder (MDD). Clinical experience suggests that rTMS treats different symptom constructs by stimulating different circuits. However, there remains a critical lack of mechanistic evidence to support putative network mechanisms of rTMS, limiting its ability to treat patients with more personalized and optimized approaches. This mechanistic proposal will first use resting-state functional connectivity (FC) MRI and customized analytic pipelines to characterize functional network topography in healthy and depressed individuals at high resolution. This data will be used to derive rTMS targets functionally situated in discrete prefrontal networks (e.g., control, default, salience, limbic/reward). Next, patients will take part in a within-subject design in which they undergo rTMS to each target on separate days. Each target will be stimulated four times on a given day, and after each stimulation changes will be measured with: (1) REST-BOLD MRI (to assess FC changes), (2) TASK-BOLD MRI (to assess changes in BOLD activation on paradigms validated to test RDoC constructs), (3) state-based questionnaires or (4) neuropsychological tests. This work will facilitate individualized neuromodulation approaches based on network topography. This will pollinate large-scale clinical trials assessing the effects of differential circuit modulation. It will also illuminate circuit-construct relationships across neuropsychiatric disorders.