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 在调节大脑连通性方面，之前发表的少数测量大脑连通性的研究和 在神经调节之后，TMS具有群体、剂量和模式特异性，其连接效应 仅限于少数几个感兴趣的先验区域。因此，迫切需要普遍的、 解释全脑水平上功能性脑连接如何变化的综合模型 在神经调节性TMS之后。因此，这笔赠款的目标是1)开发一种使用整体- 大脑对TMS诱发电场的估计以预测静息状态功能连接性的变化 在神经调节TMS之后，以及2)在一大群健康志愿者中验证这一模型 多次间歇或连续刺激(分别为ITBS和CTBS)。我们的 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 大脑皮层，使用e-field模型进行操作定义。我们有试点数据表明， TMS后rsFC前后的变化可以使用对皮层电流密度的估计来预测， 中等到较大的效果尺寸。我们的方法将是测量健康志愿者前后的rsfc。 每次3剂(5次/剂量；600次/次)的ITBS或CTB。刺激将被传递到左侧 DLPFC，靶向将基于在Sternberg工作记忆期间收集的fMRI数据进行个性化 范例。我们的主要结果衡量标准将是我们的 模特。我们这种方法的基本原理是，通过在这些剂量的ITBS之前和之后收集静息状态数据 和CTB，我们将能够量化模式(即CTBS与ITBS)和剂量(即脉冲数量)的影响 关于功能连接性的变化。这项工作具有创新性，因为它使用了一种新颖的电子场应用 建模以预测TMS管理后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.