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

基本信息

批准号：
10608983
负责人：
David Lewis Perez
金额：
$ 73.11万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
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/10608983
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 Diagnostics Research Diffusion Magnetic Resonance Imaging Disease Disease Marker Dorsal Enrollment Epidemic Etiology Evidence based treatment Exhibits Functional Imaging 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 Magnetic Resonance Imaging Medical Medicine Modeling Moods Motor Motor Cortex Multimodal Imaging National Institute of Mental Health Neurobiology Neurologist Neuronal Plasticity Neurosciences Outcome Outpatients Patient Participation 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 biopsychosocial blood oxygen level dependent care outcomes diagnostic criteria 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 neural circuit neuroimaging neuromechanism neuropsychiatric disorder neuropsychiatry novel therapeutics patient prognosis physical abuse predictive marker psychologic recruit response stria terminalis structural imaging theories treatment response white matter

项目摘要

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.

项目概要/摘要运动功能性神经障碍（mFND），也称为转换障碍，是一种常见且常见的疾病。个体出现心因性（医学上无法解释的）的致残性神经精神疾病运动症状是神经科医生和神经精神病学家最常见的病症之一。（仅次于头痛），每年用于功能障碍的医疗费用高达 2560 亿美元。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 诊断标准引发了人们的极大兴趣强调 mFND 特有的体检体征和不断增加的循证治疗方案（例如认知行为疗法、物理疗法）许多患者出现混合症状和其他症状。最初表现出一种复合症状（例如震颤），随后可能会出现不同的症状（例如虚弱）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 的运动频谱并行、会聚的结构和功能磁共振成像 (MRI)。研究结果已开始定义 mFND 的病理生理学，表征内部和外部的变化在生物心理社会模型中，显着性、多模态整合和运动控制网络。生活经历，尤其是童年虐待，是开展 mFND 研究的重要风险因素。 mFND 已确定儿童虐待负担与症状严重程度增加、预后不良、岛叶灰质体积减少，皮质边缘功能结构发生变化，特别是个体。儿童身体虐待负担的差异与运动皮层-杏仁核和运动皮层-岛叶相关这些发现代表了边缘系统高度影响的生物标志物。超过运动行为，强调了儿童虐待作为病因因素的重要性。该 R01 拨款提案以我们之前 NIMH 资助的研究为基础，旨在开展多式联运我们还进行了具有纵向成分的神经影像学研究，以神经生物学方式定义 mFND 亚型。寻求复制我们的工作并进一步表征预测治疗反应对标准的生物标志物医疗保健 (SMC) 目标 1 描述了高症状严重程度的 mFND 亚型的神经特征，而目标 2 识别高儿童身体虐待 mFND 亚型的神经特征，目标 3 研究如何进行。除了获得 6 个月的随访之外，基线神经回路特性还与 6 个月的 SMC 结果相关将使用 MRI 扫描来研究治疗反应的神经机制。定量灰质体积测定、静息态功能 MRI 和扩散张量成像，其中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，并有助于新疗法的开发通过改善对这种致残性神经精神疾病的病理生理学理解来进行治疗。