TMS-EEG investigation of prefrontal cortical excitability in depression and rTMS treatment response

项目摘要 重度抑郁症（MDD）的治疗是一个严重的临床挑战，因为近50%的抑郁症患者 患者对治疗没有完全反应，称为难治性抑郁症（TRD）。电流 抗抑郁药需要几周的时间才能发挥作用，而且目前还没有可靠的临床生物标志物来预测 治疗反应，导致不同治疗策略的多次试错尝试。两 MDD研究的主要挑战是-（i）开发更好的治疗方法和（ii）开发非侵入性的 抗抑郁治疗反应的临床有用的生物标志物。该奖项的主要目的是 研究前额叶皮层兴奋性作为抑郁症的神经生物学机制， 通过使用同步经颅磁刺激，rTMS在TRD患者中的抗抑郁作用- 脑电图（TMS-EEG）。本项目采用了一种创新的研究策略， 研究TRD患者在基线和间歇性治疗后背外侧前额叶皮层的皮质兴奋性， Theta爆发刺激（iTBS），一种最先进的FDA批准的TRD治疗。基线比较 患者，人口统计学匹配的健康对照将具有TMS-EEG。项目目标将得以实现 方法：1）研究抑郁症患者与健康对照者的前额叶皮层兴奋性 2）研究iTBS对前额叶皮层兴奋性的影响;以及3）研究基线 背外侧前额叶皮质兴奋性测量及其与抑郁症患者情绪改善的关系 TRD.这项研究的发现将加强我们对抗肿瘤机制的理解。 作用，从而促进抗抑郁药对iTBS反应的非侵入性替代标志物的开发， TRD.本工作将有助于：1）通过建立治疗标志物，实现MDD的个体化治疗 2）了解rTMS的抗抑郁作用。

PROJECT SUMMARY Treatment of Major Depressive Disorder (MDD) is a serious clinical challenge as nearly 50% of depressed patients do not fully respond to treatment, referred to as Treatment Resistant Depression (TRD). Current antidepressants take few weeks to work and further, there are no reliable clinical biomarkers available to predict treatment response which leads to several trial-and-error attempts of different treatment strategies. The two leading challenges in MDD research are – (i) developing better treatments and (ii) developing noninvasive clinically useful biomarkers of antidepressant treatment response. The main objective of this award is to investigate prefrontal cortical excitability as neurobiological mechanisms underlying depression and antidepressant effect of rTMS in patients with TRD by using concurrent Transcranial Magnetic Stimulation- Electroencephalography (TMS-EEG). This project uses an innovative research strategy by deploying TMS-EEG to study cortical excitability in dorsolateral prefrontal cortex in TRD patients at baseline and after intermittent theta burst stimulation (iTBS), a state-of-the-art FDA approved TRD treatment. For baseline comparison with patients, demographically matched healthy controls will have TMS-EEG. The project aims will be accomplished by: 1) Investigating the prefrontal cortical excitability in patients with depression compared with healthy control subjects; 2) Investigating the effect of iTBS on prefrontal cortical excitability; and 3) Investigating the baseline dorsolateral prefrontal cortical excitability measures and its relationship to improvements in mood in patients with TRD. The findings from this study will strengthen our understanding of mechanisms underlying anti-depressant action and thus facilitate development of non-invasive surrogate markers of antidepressant response to iTBS in TRD. This work will contribute to: 1) personalized medicine in MDD by establishing markers of treatment response, 2) understanding rTMS antidepressant effect.