# Defining Neurobiological Subtypes of Motor Functional Neurological Disorder

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $835,176

## Abstract

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 neurobiol...

## Key facts

- **NIH application ID:** 10172117
- **Project number:** 1R01MH125802-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** David Lewis Perez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $835,176
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172117

## Citation

> US National Institutes of Health, RePORTER application 10172117, Defining Neurobiological Subtypes of Motor Functional Neurological Disorder (1R01MH125802-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10172117. Licensed CC0.

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