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

运动功能性神经疾病症状严重程度、不良生活事件和预后的神经影像生物标志物

• 批准号: 9451009
• 负责人: David Lewis Perez
• 金额: $ 20.04万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9451009
• 关键词: Amygdaloid structure; Anterior; Applications Grants; Atrophic; Awareness; Behavior; Behavioral; Biological; Biological Markers; Brain; Caring; Characteristics; Child Abuse; Clinic; Clinical; Clinical Research; Complement; Conversion disorder; Data; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Electroencephalography; Emotions; Evaluation; Event; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Growth; Healthcare Systems; Imaging Techniques; Individual; Insula of Reil; Laboratories; Laboratory Study; Life; Limb structure; Link; Magnetic Resonance Imaging; Measures; Mediating; Medical; Modality; Modeling; Moods; Morbidity - disease rate; Motor; Movement Disorders; Network-based; Neurobiology; Neurology; Neurosciences; Outpatients; Patient Self-Report; Patients; Population; Population Research; Prevalence; Psychiatry; Psychometrics; Publishing; Quality of life; Regulation; Research; Research Training; Rest; Risk Factors; Scientist; Seizures; Sensory; Severities; Somatoform Disorders; Symptoms; Techniques; Testing; Thick; Training; Traumatic Brain Injury; Vision; Work; base; cingulate cortex; clinical phenotype; cohort; cost; disorder risk; disorder subtype; experience; gray matter; health related quality of life; imaging biomarker; imaging modality; imaging study; improved; interest; magnetic resonance imaging biomarker; midbrain central gray substance; morphometry; multimodality; nervous system disorder; neuroimaging; neuroimaging marker; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; outcome forecast; prognostic; relating to nervous system; research study; response biomarker; tool development; tractography; treatment response; white matter

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.

项目概要/摘要 功能性神经系统疾病（FND/转换障碍）是一种非常普遍且致残的疾病 神经精神状况。运动 FND 症状包括非癫痫性癫痫发作、功能性运动 疾病和功能无力。这些运动 FND 亚型的临床研究，包括研究 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 需要加强研究整合的相似之处（Perez 等人。Cogn Behav Neurol 2016；Matin & Perez 等 等人。 J Neuropsychiatry Clin Neurosci 2017）。此外，尽管运动 FND 很普遍，但人们对它知之甚少。 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 生物学上的预后和治疗反应生物标志物。跨 3 篇发表的神经生物学文章 在重点文章中，候选人提出了一个框架，通过该框架来概念化运动 FND（Perez 等人，2017）。 J Neuropsychiatry Clin Neurosci 2012，2015，Clin EEG Neurosci 2015）。建议电机FND 在介导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、内脏处理和行为调节。一个特定的 本次拨款申请的重点是 FND 症状与结构和功能相关的具体假设 显着网络内的改变，包括前岛叶、前扣带皮层、背侧 杏仁核和导水管周围灰质。该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 生物标志物 和运动 FND 的预后。贯穿本提案的目标 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、 静息态功能连接和扩散张量成像纤维束成像）用于系统地探测 脑部症状严重程度、脑部创伤负担以及脑部预后关系。该提案的新颖之处 包括对运动 FND 的全谱研究，与跨诊断方法和博士一致。 佩雷斯接受了结构和静息状态功能 MRI 技术的全面培训。这个项目 利用候选人过去探索其他神经精神疾病中大脑与症状关系的功能磁共振成像经验 疾病（Perez 等人 Psychiatry Res 2015；Psychiatry Clin Neurosci 2016），以及 Perez 博士最近的研究 已发表的 MRI 研究探讨灰质体积与症状严重程度自我报告测量的关系 运动性 FND 患者的童年虐待负担（Perez 等人，J Neurol Neurosurg Psychiatry 2017）。 本提案中提供了所有 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 促进未来综合预后和治疗研究，包括潜在的未来研究 基于基线神经影像资料的有针对性的神经调节和治疗反应生物标志物。