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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：
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
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/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

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