Novel electric-field modelling approach to quantify changes in resting state functional connectivity following theta burst stimulation

项目摘要 经颅磁刺激（TMS）目前已被FDA批准用于治疗抑郁症， 强迫症和戒烟尽管有证据表明TMS通过以下方式改善症状： 调节大脑连接，少数已发表的研究，测量大脑连接之前， 在神经调节性TMS具有人群、剂量和模式特异性之后， 在范围上限于少数先验感兴趣区域。因此，迫切需要一种普遍的， 解释全脑水平功能性大脑连接如何变化的综合模型 神经调节性TMS之后因此，这笔赠款的目标是：1）开发一个模型，使用整个- 脑对TMS诱导电场的估计，以预测静息状态功能连接的变化 在神经调节性TMS之后，以及2）在接受以下治疗的健康志愿者的大队列中验证该模型： 间歇或连续θ爆发刺激（分别为iTBS和cTBS）的多个剂量。我们 中心假设是，功能连接性的变化将随着电流密度的变化而系统地变化， 皮层，使用电场建模进行操作定义。我们有试验数据表明， TMS后的前后rsFC变化可以使用皮质处的电流密度估计来预测， 中到大的效果尺寸。我们的方法将是测量健康志愿者的rsFC前后 iTBS或cTBS的3个剂量（5个疗程/剂量; 600个脉冲/疗程）中的每一个。刺激将输送到左侧 根据斯滕贝格工作记忆期间收集的功能磁共振成像数据， 范例我们的主要结局指标是由我们的 模型我们这种方法的基本原理是，通过收集这些剂量的iTBS前后的静息状态数据， 和cTBS，我们将能够量化模式（即cTBS与iTBS）和剂量（即脉冲数）的影响 功能连接的变化。这项工作是创新的，因为它使用了一个新的应用领域， 建模以预测TMS施用后rsFC数据的变化。

Project Summary Transcranial magnetic stimulation (TMS) is currently approved by the FDA for the treatment of depression, obsessive compulsive disorder, and smoking cessation. Despite evidence that TMS improves symptoms by modulating brain connectivity, the few published studies that have measured brain connectivity before and after neuromodulatory TMS have been population-, dose-, and pattern-specific, with connectivity effects that are limited in scope to a handful a priori regions of interest. Accordingly, there is a critical need for generalized, comprehensive model that explains how functional brain connectivity changes at the whole-brain level following neuromodulatory TMS. Therefore, the objectives of this grant are to 1) develop a model using whole- brain estimates of the TMS-induced electric (e)-field to predict changes in resting state functional connectivity following neuromodulatory TMS, and 2) validate this model in a large cohort of healthy volunteers receiving multiple doses of either intermittent or continuous theta burst stimulation (iTBS and cTBS, respectively). Our central hypothesis is that changes in functional connectivity will vary systematically with the current density at the cortex, operationally defined using e-field modelling. We have pilot data suggesting that the variability in pre-post rsFC changes following TMS can be predicted using estimates of the current density at the cortex with a medium to large effect size. Our approach will be to measure rsFC in healthy volunteers before and after each of 3 doses (5 sessions/dose; 600 pulses/session) of iTBS or cTBS. Stimulation will be delivered to the left dlPFC, and targeting will be individualized based on fMRI data collected during the Sternberg working memory paradigm. Our primary outcome measure will be the percent of variability in pre-post rsFC accounted for by our model. Our rationale for this approach is that by collecting resting state data pre and post these doses of iTBS and cTBS, we will be able to quantify the effect of pattern (i.e. cTBS vs. iTBS) and dose (i.e. number of pulses) on functional connectivity changes. This work is innovative because it uses a novel application of e-field modelling to predict changes in rsFC data following TMS administration.