Defining Neurobiological Subtypes of Motor Functional Neurological Disorder

定义运动功能性神经疾病的神经生物学亚型

• 批准号: 10378665
• 负责人: David Lewis Perez
• 金额: $ 77.94万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10378665
• 关键词: Aftercare; Amygdaloid structure; Anterior; Anxiety Disorders; Applications Grants; Architecture; Biological Markers; Brain imaging; Brain scan; Caring; Child Abuse; Childhood; Clinic; Clinical; Cognitive Therapy; Complex; Conversion disorder; Coupling; DSM-V; Data; Development; Diagnostic Specificity; Diffusion Magnetic Resonance Imaging; Disease; Disease Marker; Dorsal; Enrollment; Epidemic; Etiology; Evidence based treatment; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Headache; Health Care Costs; Healthcare; Height; High Prevalence; Individual; Individual Differences; Insula of Reil; Life Experience; Link; MRI Scans; Medical; Medicine; Modeling; Moods; Motor; Motor Cortex; Multimodal Imaging; National Institute of Mental Health; Neurobiology; Neurologist; Neuronal Plasticity; Neurosciences; Outcome; Outpatients; Patients; Performance; Phenotype; Physical therapy; Population; Prevalence; Prognosis; Prognostic Marker; Property; Psychiatry; Rehabilitation therapy; Reporting; Research; Rest; Retinal blind spot; Risk Factors; Selection for Treatments; Severities; Sexual abuse; Symptoms; System; Tremor; Work; base; biopsychosocial; blood oxygen level dependent; brain magnetic resonance imaging; care outcomes; diagnostic criteria; disease prognosis; disorder subtype; follow-up; functional MRI scan; graph theory; gray matter; imaging properties; imaging study; improved; interest; magnetic resonance imaging biomarker; median forebrain bundle; midbrain central gray substance; mind control; morphometry; motor behavior; motor control; motor symptom; multimodal neuroimaging; multimodality; neglect; nervous system disorder; neural circuit; neuroimaging; neuromechanism; neuropsychiatric disorder; neuropsychiatry; novel therapeutics; patient prognosis; physical abuse; predictive marker; psychologic; recruit; relating to nervous system; response; stria terminalis; treatment response; white matter

Project Summary / Abstract Motor functional neurological disorder (mFND), also known as conversion disorder, is a common and disabling neuropsychiatric condition whereby individuals present with psychogenic (medically-unexplained) motor symptoms. mFND is amongst the most common conditions seen by neurologists and neuropsychiatrists (2nd only to headache), and $256 billion is spent annually in healthcare costs for functional disorders. Despite the high prevalence and healthcare expense, mFND has been largely neglected by the clinical neurosciences. Over the past decade, significant renewed interest has been catalyzed by the revised DSM-5 diagnostic criteria emphasizing physical exam signs specific for mFND and a growing repertoire of evidence-based treatments (e.g., cognitive behavioral therapy, physical therapy). Many patients present with mixed symptoms and others initially exhibiting one symptom complex (e.g., tremor) can later develop distinct symptoms (e.g., weakness) over the course of their illness; this emphasizes the need for a transdiagnostic research approach across the motor spectrum of FND. In parallel, convergent structural and functional magnetic resonance imaging (MRI) findings have started defining the pathophysiology of mFND, characterizing alterations within and across salience, multimodal integration and motor control networks. Within the biopsychosocial model, adverse early- life experiences, particularly childhood abuse, are important risk factors for developing mFND. Research in mFND has identified that childhood abuse burden is linked to increased symptom severity, poor prognosis, reduced insula grey matter volume, and corticolimbic functional architectural changes. Specifically, individual differences in childhood physical abuse burden correlate with motor cortex–amygdala and motor cortex–insula functional connectivity strength properties. These findings represent biomarkers of heighted limbic influence over motor behavior, highlighting the importance of childhood abuse as an etiological factor. Building upon our prior NIMH funded research, this R01 grant proposal aims to perform multimodal neuroimaging studies, with a longitudinal component, to neurobiologically define mFND subtypes. We also seek to replicate our work and further characterize biomarkers predicting treatment response to standard medical care (SMC). Aim 1 characterizes the neural signatures a high symptom severity mFND subtype, while Aim 2 identifies the neural signatures a high childhood physical abuse mFND subtype. Aim 3 investigates how baseline neural circuit properties relate to 6-month SMC outcomes, in addition to obtaining 6-month follow-up MRI scans to study neural mechanisms of treatment response. These aims will be performed using quantitative grey matter volumetry, resting-state functional MRI and diffusion tensor imaging, with the latter two approaches leveraging graph theory. The long-term objectives of this research are to identify neurobiological mFND subtypes that will guide prognosis and treatment selection, as well as aid the development of new therapeutics through an improved pathophysiological understanding of this disabling neuropsychiatric disorder.

项目总结/摘要 运动功能性神经障碍（mFND），也称为转换障碍，是一种常见的， 致残性神经精神疾病，个体表现为心因性（医学上无法解释） 运动症状mFND是神经科医生和神经精神科医生最常见的疾病之一 (2nd仅用于头痛），每年用于功能性疾病的医疗费用为2560亿美元。尽管 由于高患病率和医疗费用，mFND在很大程度上被临床神经科学所忽视。 在过去的十年中，修订后的DSM-5诊断标准重新引起了人们的关注 强调mFND特异性的体格检查体征和越来越多的循证治疗 (e.g.,认知行为疗法、物理疗法）。许多患者表现为混合症状， 最初表现出一种综合症状（例如，震颤）可随后发展出不同的症状（例如，弱点） 在他们的疾病过程中，这强调了跨诊断研究方法的必要性。 FND的运动频谱。在并行，会聚结构和功能磁共振成像（MRI） 研究结果已经开始定义mFND的病理生理学，表征内部和之间的变化， 显著性、多模态整合和运动控制网络。在生物心理社会模型中，不利的早期- 生活经历，特别是童年虐待，是发展mFND的重要风险因素。研究 mFND已经确定，儿童期虐待负担与症状严重程度增加，预后不良， 脑灰质体积减少和皮质边缘功能结构改变。具体而言，个人 儿童期身体虐待负担差异与运动皮质-杏仁核和运动皮质-杏仁核相关 功能连接强度特性。这些发现代表了边缘系统影响增强的生物标志物 而不是运动行为，突出了儿童虐待作为病因的重要性。 在我们之前的NIMH资助的研究的基础上，这个R 01赠款提案旨在执行多模式 神经影像学研究，纵向组成部分，神经生物学定义mFND亚型。我们也 寻求复制我们的工作，并进一步表征预测标准治疗反应的生物标志物， 医疗保健（SMC）。目的1将神经特征描述为高症状严重程度mFND亚型，而 目的2确定神经签名高儿童身体虐待mFND亚型。目标3研究如何 除了获得6个月随访外，基线神经回路特性与6个月SMC结局相关 MRI扫描以研究治疗反应的神经机制。这些目标将使用 定量灰质体积测定、静息态功能MRI和扩散张量成像，后两者 利用图论的方法。这项研究的长期目标是确定神经生物学 mFND亚型将指导预后和治疗选择，以及帮助开发新的 通过改善对这种致残性神经精神障碍的病理生理学理解来治疗。