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

TMS-EEG 研究抑郁症前额皮质兴奋性和 rTMS 治疗反应

• 批准号: 9896462
• 负责人: RAYMOND Y CHO
• 金额: $ 20.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-13 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896462
• 关键词: Action Potentials; Address; Antidepressive Agents; Award; Biological Markers; Brain; Chemosensitization; Clinical; Depressed mood; Development; Disease; Electroencephalography; Emotional; Emotions; Equilibrium; FDA approved; Functional disorder; Human; Impairment; Investigation; Ketamine; Knowledge; Left; Link; Major Depressive Disorder; Measures; Mental Depression; Mental disorders; Moods; Motor; Motor Cortex; Neurologic; Neuronal Plasticity; Neurons; Patients; Population; Prediction of Response to Therapy; Prefrontal Cortex; Regulation; Research; Safety; Surrogate Markers; Synapses; Techniques; Transcranial magnetic stimulation; Treatment Efficacy; Work; antidepressant effect; clinical biomarkers; depressed patient; functional disability; health economics; improved; indexing; innovation; neural circuit; neurobiological mechanism; neuroregulation; novel; personalized medicine; repetitive transcranial magnetic stimulation; response; specific biomarkers; success; treatment choice; treatment response; treatment strategy; treatment-resistant depression

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.

项目摘要 重大抑郁症（MDD）的治疗是严重的临床挑战 患者对治疗没有完全反应，称为抗治疗抑郁症（TRD）。当前的 抗抑郁药需要几周的时间才能工作，而且没有可靠的临床生物标志物可以预测 治疗反应会导致不同的治疗策略的多次反复尝试。两个 MDD研究中的主要挑战是 - （i）开发更好的治疗方法，以及（ii）发展无创的 抗抑郁治疗反应的临床上有用的生物标志物。该奖项的主要目的是 研究前额叶皮质令人兴奋，作为抑郁症和抑郁症的神经生物学机制 通过使用并发的经颅磁刺激 - 脑电图（TMS-EEG）。该项目通过部署TMS-EEG使用创新的研究策略 研究基线和间歇性后TRD患者背外侧前额叶皮层皮质兴奋 Theta爆发刺激（ITB）是最先进的FDA批准的TRD处理。用于基线比较 患者，人口匹配的健康对照将具有TMS-EEG。该项目的目标将实现 作者：1）与健康对照相比，研究抑郁症患者的前额叶皮质刺激性 受试者； 2）研究ITB对前额叶皮质刺激的影响； 3）调查基线 背侧前额叶皮质令人兴奋措施及其与患者与情绪的关系有所改善 trd。这项研究的发现将加强我们对抗抑郁剂基础机制的理解 作用，从而促进抗抑郁反应的非侵入性替代标志物的发展 trd。这项工作将有助于：1）MDD中的个性化药物通过建立治疗标记 反应，2）了解RTMS抗抑郁作用。