Leveraging network control theory to explain individual differences to non-invasive brain stimulation

项目总结/摘要 在非侵入性脑刺激使用增长的令人兴奋的时代， 随着越来越多的FDA批准和设计用于探测或 以奇妙的新方式调节大脑。这种日益增长的热情的问题是， 研究评估了经颅磁刺激（TMS）等工具如何诱导功能性 在整个人类大脑中激活，特别是在运动系统之外。神经调节成为可能 通过管理重复TMS（rTMS）的列车更是知之甚少，因为它需要捕获 大脑中的动态变化是功能变化的根源。我们已经开发出一种 在记录功能性MRI时通过单脉冲TMS传送的电路通信的分析协议， 跟踪TMS对各种前额叶皮质靶点的脑效应。我们开始测量这个电路- 在神经调节rTMS之前和之后的特定通信流到同一电路，以量化 这些急性大脑干预所产生的动力学。通过拟议的研究，我们计划优化 TMS靶向两个脑网络：额下回至杏仁核和外侧前额叶至膝下区 前扣带皮层通过对每个人的功能性MRI成像进行个性化定位，我们相信， 我们可以优化我们影响大脑的能力，最终更好地理解行为的变化， 对TMS的回应一组关键的拟议指标，用于建立对TMS影响的更坚定的理解， 大脑将是两种不同的假设剂量/反应关系： 1)回路激活将作为绝对刺激水平的函数增加，2）回路通信将 作为神经调节脑过程中传递的rTMS脉冲累积数量的函数进行调制 刺激. 3)最后，为了增加我们在目标电路中捕获电路完整性分层样本的机会， 被认为在情感障碍中被破坏的通路， (who否则将是健康的）最近将被诊断患有重度抑郁症。 意义：我们对脑对TMS反应的综合分析也将包括TMS探针反应 在应用神经调节性TMS之前、期间和之后记录静息fMRI。这一战略将产生 在了解非侵入性脑刺激如何影响人类大脑功能方面迈出了重要一步 这可以成为工具开发和新的基于脑的治疗的方法和理论基础。

Project Summary / Abstract In an exciting era of growth in the use of non-invasive brain stimulation, new methods and applications are being disseminated widely with an increasing number of FDA approvals and equipment designed to probe or modulate the brain in fascinating new ways. The problem with this growing enthusiasm is that there are too few studies that have evaluated how tools such as transcranial magnetic stimulation (TMS) induce functional activation throughout a human brain, especially outside of the motor system. Neuromodulation made possible by administering trains of repetitive TMS (rTMS) is even more poorly understood since it requires capturing dynamic changes in the brain that are at the root of proposed changes in function. We have developed a protocol for assaying circuit communication by single pulse TMS delivered while recording functional MRI to follow brain wide effects of TMS to various prefrontal cortex targets. We are beginning to measure this circuit- specific communication flow before and after neuromodulatory rTMS to the same circuit to quantify changes in dynamics resulting from these acute brain interventions. With the proposed research, we plan to optimize targeting of two brain networks with TMS: inferior frontal gyrus to amygdala and lateral prefrontal to subgenual anterior cingulate cortex. By individualizing targeting from each person's functional MRI mapping, we believe that we can optimize our ability to affect the brain and ultimately better understand variability in behavioral response to TMS. A key set of proposed metrics for establishing a firmer understanding of TMS effects on the brain will be two different hypothesized dose/response relationships: 1) Circuit activation will increase as a function of absolute stimulation level and 2) Circuit communication will be modulated as a function of the cumulative number of rTMS pulses delivered during neuromodulatory brain stimulation. 3) Finally, to increase our chances of capturing a stratified sample of circuit integrity in the targeted pathways that are thought to be disrupted in affective disorders, a sub-sample of the recruited participants (who will otherwise be healthy) will be recently diagnosed with major depressive disorder. Significance: Our comprehensive assay of brain response to TMS will include TMS probe responses as well as resting fMRI recorded before, during, and after application of neuromodulatory TMS. This strategy will yield a significant step forward in understanding how non-invasive brain stimulation affects human brain functioning that can be a methodological and theoretical base for tool development and novel brain-based therapeutics.