Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders

Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Clinical research across these motor FND subtypes, including research studies from the candidate's laboratory, suggest that these populations share many clinical and phenotypic similarities that warrant increased research integration. Furthermore, despite the prevalence of motor FND, little is known about the underlying pathophysiology of this condition, which is a prerequisite for the development of biologically informed prognostic and treatment response biomarkers. Across 3 published neurobiologically focused articles, the candidate proposed a framework through which to conceptualize motor FND. It is suggested that motor FND develops in the context of structural and functional alterations in neurocircuits mediating emotion awareness/expression, bodily awareness, viscerosomatic processing and behavioral regulation. The overall goal of this project is to comprehensively investigate structural and functional magnetic resonance imaging (MRI) biomarkers of prognosis across motor FND. Multimodal structural and functional MRI techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) will be used to systemically probe brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach.

Functional Neurological Disorder (FND) (Conversion Disorder) is a poorly understood and prevalent somatoform disorder, making up 16% of outpatient neurology referrals. Patients with motor FND (mFND) are difficult to treat, result in major morbidity, and are costly to the US. An estimated $256 billion is spent annually treating this population. mFND includes Nonepileptic Seizures (NES), Functional Movement Disorders (FMD) and Functional Weakness (FW). An impediment to managing mFND is the lack of a neurobiological understanding for this disorder. The diagnosis of mFND is currently based on qualitative aspects of behaviors, which may be difficult to interpret, and the absence of findings characteristic of other neuropsychiatric disorders on laboratory studies such as electroencephalography (EEG) and magnetic resonance imaging (MRI).

A major step forward would be the identification of neuroimaging biomarkers for mFND. mFND is understudied compared to other disorders, but recent studies point to distributed neurocircuit alterations associated with mFND. This project aims to advance our biological understanding of mFND by investigating neuroimaging biomarkers linked to prognosis. An improved understanding of the pathophysiology of mFND will provide a critical step in elucidating diagnostic, prognostic and treatment response biomarkers.

Aim:

Identify structural and functional biomarkers of prognosis at 6-months in patients with motor functional neurological disorders receiving an updated standard of care.

H1: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline gray matter in limbic-paralimbic regions, particularly those part of the salience network.

H2: Favorable mFND prognosis at 6 months post initial evaluation will be predicted by the degree of preserved baseline resting-state functional connectivity in limbic/paralimbic areas, particularly those part of the salience network.

H3: Favorable mFND prognosis at 6 months will correlate with the degree of preserved baseline cingulum bundle and cingulum-insular tract integrity.

Eligibility Criteria:
Inclusion Criteria:

* clinically established motor functional neurological disorder, including individuals with functional movement disorders, functional limb weakness and psychogenic nonepileptic seizures

Exclusion Criteria:

* active suicidality
* major medical/neurological comorbidities with known central nervous system (CNS) consequences
* active drug use or alcohol dependence
* known history of a primary psychotic disorder