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

项目总结/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促进特定症状的形成。这表明有机会 通过调节特定回路来治疗特定症状。重复经颅磁刺激（rTMS） 能够进行回路特异性神经调节。它也是一个既定的治疗严重抑郁症 （MDD）。临床经验表明，rTMS治疗不同的症状结构，刺激不同的 电路.然而，仍然严重缺乏支持假定网络的机制证据 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。 这种机制的建议将首先使用静息状态功能连接（FC）MRI和定制的分析 管道，以高分辨率表征健康和抑郁个体的功能网络拓扑。 该数据将用于导出功能上位于离散前额网络中的rTMS目标（例如，控制器， 默认、显著性、边缘/奖励）。接下来，患者将参加一项受试者内设计， 在不同的日子对每个目标进行rTMS。每个目标将在给定的一天刺激四次，每次刺激后， 刺激变化将通过以下方式测量：（1）REST-BOLD MRI（评估FC变化），（2）TASK-BOLD MRI（评估经验证以测试RDoC结构的范例上BOLD激活的变化），（3）基于状态的 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 基于网络拓扑的方法。这将为大规模的临床试验提供花粉， 差分电路调制它还将阐明神经精神病学中的回路结构关系。 紊乱

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.