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， 情绪障碍的精神病理学知识，这将有助于他发展成为一个独立的调查员 使用个性化的神经成像和非侵入性脑刺激技术，1）精确了解 情绪障碍中的脑网络功能障碍，以及2）开发用于增强潜在参与的方法 单个患者的治疗目标。PI已经组建了一个情绪障碍专家团队，人类 神经成像，和非侵入性脑刺激，以帮助他完成这项建议的目的和培训 这将为他的长期职业目标提供必要的经验。拟议项目将在 在威尔康奈尔医学（WCM）和利用智力环境在大脑思维研究所 （BMRI）和使用WCM的核心设施，包括Sackler Institute和Citigroup Biomedical Imaging 中心 该提案的重点是严重抑郁症（MDD），这是导致残疾的主要原因之一 国际吧重复经颅磁刺激（rTMS）是一种很有前途的治疗药物抵抗性 但其抗抑郁机制尚不完全清楚，特别是在神经回路水平 和大规模的大脑网络，使提高其在单个患者中的治疗潜力的努力变得复杂。的 这一建议的中心假设是，10 Hz rTMS被施加到与效价有关的大脑网络， MDD患者的加工缺陷，称为显著性网络，降低了对厌恶的回路反应性。 刺激。PI将使用最先进的技术进行个性化的功能性大脑网络映射， 使用并发TMS功能磁共振成像测量显著性网络的参与。PI还将评价rTMS是否 给予的显着性网络拯救电路功能障碍和效价处理缺陷。 拟议的培训计划补充了本建议书的研究目标，包括正式的教学法、实践 由非侵入性脑刺激领先专家举办的研讨会，研究合作，将提供 PI具有五个领域的知识和技能：1）心境障碍精神病理学; 2）新的统计和 计算方法; 3）新的研究工具; 4）导师制; 5）科学交流。完成本 该提案将产生实施K供资机制所需的初步数据，并将为 稍后在PI中开发针对情绪障碍的神经生物学信息、个性化rTMS干预措施 事业 !

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. !