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.

项目摘要/摘要 运动性功能性神经功能障碍(MFND)，又称转换障碍，是一种常见的 致残的神经精神状态，即个体存在心理原因(医学上无法解释) 运动症状。MFND是神经学家和神经精神病学家看到的最常见的情况之一 (仅次于头痛)，每年用于功能性障碍的医疗费用为2560亿美元。尽管 MFND的高患病率和医疗费用在很大程度上被临床神经科学所忽视。 在过去的十年里，修订的DSM-5诊断标准重新引起了人们的极大兴趣 强调mFND特有的体检体征和越来越多的循证治疗方法 (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 最初表现出一种复杂的症状(例如，震颤)，后来可能会发展成明显的症状(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、融合的结构和功能磁共振成像(MRI) 这些发现已经开始定义mFND的病理生理学，描述了mFND内部和跨区域的变化 突出、多模式集成和电机控制网络。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，是发展成mFND的重要风险因素。研究领域 MFND已经发现，儿童虐待负担与症状严重程度增加、预后不良、 脑岛灰质体积减少，皮质边缘功能构筑改变。具体而言，个人 儿童期身体虐待负荷的差异与运动皮质-杏仁核和运动皮质-岛叶相关 功能连接强度属性。这些发现代表了边缘高度影响的生物标志物。 关于运动行为，强调了儿童期虐待作为病因因素的重要性。 在我们之前NIMH资助的研究的基础上，这份R01拨款提案旨在执行多式联运 神经影像研究，包括纵向部分，用于神经生物学定义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记物 医疗(SMC)。目的1将神经特征描述为高症状严重程度的mFND亚型，而 目的2鉴定神经特征是一种高度儿童期身体虐待的mFND亚型。AIM 3调查了 除了获得6个月的随访外，基线神经回路特性还与6个月的SMC结果有关 核磁共振扫描研究治疗反应的神经机制。这些目标将通过以下方式实现 定量灰质体积测量、静息状态功能磁共振成像和扩散张量成像 利用图论的方法。这项研究的长期目标是确定神经生物学 指导预后和治疗选择的mFND亚型，以及帮助开发新的 通过对这种致残性神经精神障碍的更好的病理生理学理解来治疗。