Defining Neurobiological Subtypes of Motor Functional Neurological Disorder

点击翻译按钮获取中文摘要

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.