Neuroimaging Biomarkers of Symptom Severity, Adverse Life Events and Prognosis in Motor Functional Neurological Disorders

项目摘要/摘要 功能性神经功能障碍(FND/转换障碍)是一种非常普遍和致残的疾病 神经精神疾病。运动性FND症状包括非癫痫发作、功能性运动 精神障碍和功能虚弱。这些运动FND亚型的临床研究，包括研究 来自候选人实验室的研究表明，这些人群有许多共同的临床和表型 需要增加研究整合的相似性(Perez等人)。Cogn Behav Neurol 2016；Matin&Perez et 艾尔J神经精神病学Clin Neurosci 2017)。此外，尽管运动性FND很普遍，但人们对此知之甚少 关于这种情况的潜在神经病理生理学，这是发展的先决条件 生物知情的预后和治疗反应生物标记物。在神经生物学方面发表了3篇论文 在重点文章中，候选人提出了一个框架，通过这个框架来概念化汽车FND(Perez等人)。 J神经精神病学Clin Neurosci 2012,2015，Clin EEG Neurosci 2015)。建议使用马达FND 在调节情绪的神经回路的结构和功能变化的背景下发展 意识/表达、身体意识、内脏躯体加工和行为调节。一种特殊的 这项拨款申请的重点是关于FND症状与结构和功能有关的具体假设 突起网络内的改变，包括前岛叶、前扣带回皮质、背侧 扁桃体和导水管周围灰色。这项提案的总体目标是全面调查 症状严重程度、不良生活事件负担(FND危险因素)的结构和功能MRI生物标记物 以及运动FND的预后。跨本提案的目标1-3，多模式结构和功能 磁共振成像(MRI)技术(包括基于体素的形态测量、皮质厚度、 静息状态功能连通性和扩散张量成像技术)用于系统探测 脑症状严重程度、脑创伤负担与脑预后的关系。这项提议的新方面 包括对运动FND的全谱研究，与跨诊断方法和DR一致。 佩雷斯的训练全面补充了结构和静息状态的功能磁共振技术。这个项目 利用应聘者过去的fMRI经验探索其他神经精神科患者的脑-症状关系 精神障碍(Perez等人精神病学Res 2015；精神病学Clin Neurosci 2016)，以及佩雷斯博士最近的 已发表的MRI研究探索灰质体积与症状严重程度自我报告的相关性 运动性FND患者的儿童期虐待负担(Perez等人)。J Neurol NeuroSurg精神病学2017)。 本提案提供了所有3个AIMS的试点数据。这些对汽车FND的研究将确定跨诊断 神经生物标记物与症状严重程度、不良生活事件和预后有关。这个项目的结果将是 催化未来全面的预后和治疗研究，包括潜在的未来研究 基于基线神经影像资料的定向神经调节和治疗反应生物标记物。

PROJECT SUMMARY/ABSTRACT Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Clinical research across these motor FND subtypes, including research studies from the candidate's laboratory, suggest that these populations share many clinical and phenotypic similarities that warrant increased research integration (Perez et al. Cogn Behav Neurol 2016; Matin & Perez et al. J Neuropsychiatry Clin Neurosci 2017). Furthermore, despite the prevalence of motor FND, little is known about the underlying neuropathophysiology of this condition, which is a prerequisite for the development of biologically informed prognostic and treatment response biomarkers. Across 3 published neurobiologically focused articles, the candidate proposed a framework through which to conceptualize motor FND (Perez et al. J Neuropsychiatry Clin Neurosci 2012, 2015, Clin EEG Neurosci 2015). It is suggested that motor FND develops in the context of structural and functional alterations in neurocircuits mediating emotion awareness/expression, bodily awareness, viscerosomatic processing and behavioral regulation. A particular focus of this grant application is the specific hypothesis that FND symptoms relate to structural and functional alterations within the salience network, which includes the anterior insula, anterior cingulate cortex, dorsal amygdala and periaqueductal gray. The overall goal of this proposal is to comprehensively investigate structural and functional MRI biomarkers of symptom severity, adverse life event burden (a FND risk factor) and prognosis across motor FND. Across aims 1-3 of this proposal, multimodal structural and functional magnetic resonance imaging (MRI) techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) are used to systemically probe brain-symptom severity, brain-trauma burden and brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach and Dr. Perez's training in the full complement of structural and resting state functional MRI techniques. This project leverages the candidate's past fMRI experience probing brain-symptom relationships in other neuropsychiatric disorders (Perez et al. Psychiatry Res 2015; Psychiatry Clin Neurosci 2016), as well as Dr. Perez's recently published MRI study probing gray matter volume associations with self-report measures of symptom severity and childhood abuse burden in patients with motor FND (Perez et al. J Neurol Neurosurg Psychiatry 2017). Pilot data for all 3 aims is presented in this proposal. These studies in motor FND will identify trans-diagnostic neural biomarkers linked to symptom severity, adverse life events and prognosis. The results of this project will catalyze future comprehensive prognostic and treatment research including the potential future study of targeted neuromodulation and treatment response biomarkers based on baseline neuroimaging profiles.