Targeting salience network dysfunction in depression with individualized brain network mapping and TMS

摘要 拟议的F32职业发展奖的目标是为PI提供技术技能和 心境障碍精神病理学知识，有助于他成为一名独立的调查人员 使用个性化神经成像和非侵入性脑刺激技术精确了解1) 情绪障碍的脑网络功能障碍和2)开发增强潜在参与的方法 单身患者的治疗目标。私家侦探组建了一个研究情绪障碍的专家团队， 神经成像和非侵入性脑刺激，以帮助他完成这项提议和培训的目标 这项计划将为他的长期职业目标提供必要的经验。拟议中的项目将进行 在威尔·康奈尔医学院(WCM)工作，并利用大脑心理研究所的知识环境 (BMRI)和访问WCM的核心设施，包括萨克勒研究所和花旗集团生物医学成像 中心。 这项提案的重点是严重抑郁障碍(MDD)，这是导致残疾的主要原因之一 全世界。重复经颅磁刺激(RTMS)是治疗药物耐药的一种很有前途的方法 MDD，但其抗抑郁机制尚不完全清楚，特别是在神经回路水平上 和大规模的大脑网络，使增强其在单身患者中的治疗潜力的努力复杂化。这个 这一提议的中心假设是，对大脑网络进行10赫兹rTMS与价态有关 MDD患者的加工缺陷，称为显著网络，降低了对厌恶的回路反应性 刺激物。PI将使用最先进的技术进行个性化的功能大脑网络映射和 使用并发TMS-fMRI测量显著网络的参与度。PI还将评估rTMS是否 应用到突显网络可以挽救回路功能障碍和价处理缺陷。 拟议的培训计划通过正式的教学实践补充了本计划的研究目标。 由领先的非侵入性脑刺激专家举办的研讨会，研究合作将提供 具有五个领域的知识和技能的PI：1)情绪障碍精神病理学；2)新的统计和 计算方法；3)新的研究工具；4)指导；5)科学交流。完成这项工作 提案将产生推行K筹资机制所需的初步数据，并将为 开发神经生物学知情的、个性化的rTMS干预措施，用于稍后在PI‘s中治疗情绪障碍 职业生涯。 好了！

Abstract The goals of the proposed F32 Career Development Award are to provide the PI with a technical skillset and knowledge of mood disorder psychopathology that will facilitate his developing into an independent investigator using individualized neuroimaging and non-invasive brain stimulation technologies to 1) precisely understand brain network dysfunction in mood disorders and 2) develop methods for enhancing engagement of potential treatment targets in single patients. The PI has assembled a team of experts on mood disorders, human neuroimaging, and non-invasive brain stimulation to help him complete the aims of this proposal and a training plan that will provide experience essential to his long-term career goals. The proposed project will be conducted at Weill Cornell Medicine (WCM) and leverage the intellectual environment at Brain Mind Research Institute (BMRI) and access to the core facilities of WCM, including Sackler Institute and Citigroup Biomedical Imaging Center. This proposal is focused on Major Depressive Disorder (MDD), one of the leading causes of disability worldwide. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for medication-resistant MDD but its antidepressant mechanisms are incompletely understood, especially at the level of neural circuits and large-scale brain networks, complicating efforts to enhance its treatment potential in single patients. The central hypothesis of this proposal is that 10 Hz rTMS administered to a brain network implicated in valence processing deficits in patients with MDD, termed the salience network, decreases circuit responsivity to aversive stimuli. The PI will use state-of-the-art technologies for individualized functional brain network mapping and measure engagement of the salience network using concurrent TMS-fMRI. The PI will also evaluate if rTMS administered to the salience network rescues circuit dysfunction and valence processing deficits. The proposed training plan complements the research aims of this proposal with formal didactics, hands-on workshops run by leading experts on non-invasive brain stimulation, research collaborations, that will provide the PI with knowledge and skills in five areas: 1) mood disorder psychopathology; 2) new statistical and computational methods; 3) new investigational tools; 4) mentorship; 5) scientific communication. Completing this proposal will generate preliminary data necessary for pursuing a K funding mechanism and will set-the-stage for developing neurobiologically informed, personalized rTMS interventions for mood disorders later in the PI’s career. !