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

项目总结/摘要 功能性神经障碍（FND/转换障碍）是一种高度流行和致残的疾病， 神经精神状况运动FND症状包括非癫痫性发作、功能性运动 疾病和功能性虚弱。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，这些人群具有许多临床和表型特征， 相似之处，保证增加研究整合（佩雷斯等人Cogn Behav Neurol 2016;马丁和佩雷斯等人 al. J Neuropsychiatry Clin Neurosci 2017）。此外，尽管运动性FND的流行， 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， 生物学信息的预后和治疗反应生物标志物。在3篇发表的神经生物学研究中 重点的文章，候选人提出了一个框架，通过它来概念化运动FND（佩雷斯等人。 J Neuropsychiatry Clin Neurosci 2012，2015，Clin EEG Neurosci 2015）。建议运动FND 在调节情绪的神经回路的结构和功能改变的背景下发展 意识/表达、身体意识、内脏躯体加工和行为调节。特定 这项拨款申请的重点是FND症状与结构和功能相关的具体假设， 显著性网络内的改变，包括前扣带皮层、前扣带皮层、背侧皮层、前扣带皮层和背侧皮层。 杏仁核和导水管周围灰质。这份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风险因素）的结构和功能MRI生物标志物 和运动神经功能缺损的预后。在本提案的目标1-3中， 磁共振成像（MRI）技术（包括基于体素的形态测定，皮质厚度， 静息状态功能连接和弥散张量成像纤维束成像）用于系统地探测 脑症状严重程度、脑创伤负荷和脑预后关系。本提案的新颖之处 包括对运动性FND全谱的研究，这与跨诊断方法一致。 佩雷斯的培训，在结构和静息状态功能磁共振成像技术的全面补充。这个项目 利用候选人过去的功能磁共振成像经验，在其他神经精神疾病中探索大脑症状关系 疾病（Perez et al. Psychiatry Res 2015; Psychiatry Clin Neurosci 2016），以及Perez博士最近 一项已发表的MRI研究，探讨了灰质体积与症状严重程度的自我报告指标之间的关系 运动FND患者的儿童期虐待负担（Perez et al. J Neurol Neurosurg Psychiatry 2017）。 本提案提供了所有3个目标的试点数据。这些运动FND的研究将确定跨诊断 与症状严重程度、不良生活事件和预后相关的神经生物标志物。该项目的成果将 促进未来全面的预后和治疗研究，包括未来可能的研究， 靶向神经调节和基于基线神经成像概况的治疗反应生物标志物。

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.