Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders
Study Details
Study Description
Brief Summary
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 neuropathophysiology 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.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
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 neuropathophysiology 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 cingulo-insular tract integrity.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Motor Functional Neurological Disorder. The cohort will consist of patients with clinically established motor functional neurological disorder, which includes individuals with functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Patients will be receiving the standard of care within the Massachusetts General Hospital (MGH) Functional Neurological Disorders Clinic. The updated standard of care that patient's receive in the MGH Functional Neurological Disorders Clinic includes the following: Delivery of a positive "rule-in" diagnosis of functional neurological disorder Individuals are provided with educational materials on functional neurological disorders Referred to physical therapy and/or occupational therapy as clinically indicated FND related cognitive behavioral therapy (CBT) referral when appropriate Psychotropic medication management based on standard psychiatric care |
Other: Standard of Care
The standard of care interventions for Functional Neurological Disorders (FND) include:
delivery of a rule-in diagnosis
providing educational materials
referring to physical therapy (PT) and/or occupational therapy (OT) as clinically indicated
referring to FND-related cognitive behavioral therapy (CBT)
psychotropic medication management based on standard psychiatric care
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Outcome Measures
Primary Outcome Measures
- Gray Matter Volume Biomarkers of 6 Month Prognosis as measured by Voxel Based Morphometry [2-4 years]
Correcting for multiple comparisons in structural analyses, baseline structural grey matter volumes in limbic/paralimbic regions (particularly those affiliated with the salience network), would be predictive of clinical outcome in individuals receiving the standard of care at 6 months.
- Resting State Functional Connectivity Strength Biomarkers of 6 Month Prognosis [3-5 years]
Correcting for multiple comparisons in resting state connectivity analyses, baseline functional connectivity strength (Pearson correlation coefficients) across limbic/paralimbic regions (particularly those affiliated with the salience network), would be predictive of clinical outcome in individuals receiving the standard of care at 6 months.
- The integrity of specific white matter tracts (fractional anisotropy) as measured by diffusion tensor imaging (DTI) tractography will relate to 6-month prognosis [3-5 years]
Baseline integrity of the cingulum bundle and cingulate-insular tracts, as measured by fractional anisotropy, would be predictive of 6 month prognosis in patients with Functional Neurological Disorders (FND) receiving the standard of care.
Eligibility Criteria
Criteria
Inclusion Criteria:
- clinically established motor functional neurological disorder, including individuals with functional movement disorders, functional limb weakness and psychogenic nonepileptic seizures
Exclusion Criteria:
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active suicidality
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major medical/neurological comorbidities with known central nervous system (CNS) consequences
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active drug use or alcohol dependence
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known history of a primary psychotic disorder
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
Sponsors and Collaborators
- Massachusetts General Hospital
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 1K23MH111983-01A1