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：
10172117
负责人：
David Lewis Perez
金额：
$ 83.52万
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/10172117
关键词：
Aftercare Amygdaloid structure Anterior Anxiety Disorders Applications Grants Architecture Biological Biological Markers Brain imaging Brain scan Caring Child Abuse Childhood Clinic Clinical Cognitive Therapy Complex Conversion disorder Coupling DSM-V Data Development Diagnostic 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 Magnetic Resonance Imaging 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 Prevalence Prognosis Prognostic Marker Property Psychiatry Rehabilitation therapy Reporting Research Rest Retinal blind spot Risk Factors Selection for Treatments Severities Sexual abuse Structure Symptoms System Tremor Work base biopsychosocial blood oxygen level dependent care outcomes 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 multimodality neglect nervous system disorder neural circuit neuroimaging neuromechanism neuropsychiatric disorder neuropsychiatry novel therapeutics physical abuse predictive marker psychologic recruit relating to nervous system response stria terminalis 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.

项目摘要 /摘要运动功能性神经系统障碍（MFND），也称为转化障碍，是一种常见，残疾神经精神病疾病，使人患有心理源（医学上没有解释）运动症状。 MFND是神经科医生和神经精神科医生看到的最常见的疾病之一（仅到标题第二），每年在功能障碍的医疗保健费用上花费了2560亿美元。尽管 MFND的高患病率和医疗费用很大程度上被临床神经科学忽略了。在过去的十年中，修订后的DSM-5诊断标准催化了重大的新兴趣强调特定于MFND的身体检查迹象以及循证疗法的日益增长的曲目（例如，认知行为疗法，物理疗法）。许多患者出现混合症状，其他患者最初表现出一种症状复合物（例如，震颤）会稍后出现不同的症状（例如，弱点）在他们的病过程中；这强调了在整个过程中都需要进行经诊断的研究方法 FND的运动光谱。并行，收敛的结构和功能磁共振成像（MRI）发现已经开始定义MFND的病理生理学，表征了内部和跨越的改变显着性，多模式集成和电动机控制网络。在生物心理社会模型中，早期不良生活经历，尤其是童年时期，是发展MFND的重要危险因素。研究 MFND确定伯恩伯恩与症状严重程度增加，预后不良有关，减少了岛灰质体积和皮质脂质的功能架构变化。具体来说，个人儿童身体虐待的差异伯恩与运动皮层 - amygdala和运动皮层 - insula相关功能连接强度特性。这些发现代表了边缘影响越高的生物标志物关于运动行为，强调了儿童虐待作为病因的重要性。在我们先前的NIMH资助研究的基础上，此R01赠款提案旨在执行多模式神经影像学研究，具有纵向成分，以神经生物学定义MFND亚型。我们也是寻求复制我们的工作并进一步特征生物标志物，以预测对标准的治疗反应医疗保健（SMC）。 AIM 1个字符神经签名高症状严重程度MFND子类型，而 AIM 2标识了神经特征的童年时代较高的身体虐待MFND子类型。 AIM 3调查了如何基线神经回路的特性与6个月的SMC结果有关，除了获得6个月的随访 MRI扫描以研究治疗反应的神经机制。这些目标将使用定量的灰质体积，静止状态功能性MRI和扩散张量成像，后两个使用图理论的方法。这项研究的长期目标是确定神经生物学 MFND子类型将指导促使病和治疗选择，并有助于开发新的通过改善对这种残疾神经精神疾病的病理生理理解的治疗方法。