Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 3/13/2019 |
| Start Date: | September 1, 2017 |
| End Date: | August 31, 2022 |
| Contact: | David L Perez, MD, MMSc |
| Email: | dlperez@partners.org |
| Phone: | 617-724-7243 |
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.
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.
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.
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.
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
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Phone: 617-724-7243
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