Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders
Condition: Conversion Disorder
MeSH terms: Nervous System Diseases; Conversion Disorder; Hysteria; Dissociative Disorders
Study type: Observational

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 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.
    

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 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.
    

Intervention name(s): Standard of Care
Intervention type(s): Other
Intervention description(s): 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
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Recruitment will occur from patients receiving care in the Massachusetts General Hospital
        (MGH) Functional Neurological Disorders Clinic
      
Keywords: Functional Neurological Disorder; Functional Movement Disorder; Psychogenic Nonepileptic Seizures; Functional Limb Weakness