Pilot Study of Cognitive Behavioral Therapy-Informed Physical Therapy Intervention in Functional Neurological Disorders

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
Functional Movement Disorders (FMD), Functional Weakness (FW) and Psychogenic Nonepileptic
Seizures (PNES).

This project will investigate brain network profiles associated with and predictive of
clinical improvement in patients with Functional Neurological Disorder (FND) following a
12-week cognitive behavioral therapy-informed physical therapy treatment program. Integrated
physical therapy along with self-guided cognitive behavioral therapy is usual care for
patients with FND experiencing motor symptoms at the Massachusetts General Hospital. Patients
with motor FND experience significant impairment and often face issues with treatment
management. Recent advancements in clinical research, catalyzed by new diagnostic criteria
and an updated care model, have emphasized physical therapy and cognitive behavioral therapy
as important evidence-based treatments for this population. Additionally, developments in
neuroscience have allowed for a more comprehensive understanding of the neurobiology of FND.
However, there has been limited investigation of longitudinal biomarkers associated with and
predictive of treatment response, highlighting the need for an improved understanding of
neurobiological changes underlying prognosis in FND.

We propose acquiring structural and functional brain imaging data in combination with
psychometric assessments and patient chart review to examine neurobiological mechanisms of
associated with participation in a cognitive behavioral therapy-informed physical therapy
treatment program for patients with FND.

Primary Aim and Hypotheses The primary goal of this study is to provide structural and
functional biomarkers related to and predictive of treatment response and clinical outcome in
patients with motor FND following a 12-week cognitive behavioral therapy-informed physical
therapy treatment program (usual care).

Specific Aim 1:

SA1) Identify structural MRI biomarkers linked to and predictive of improvement following
cognitive behavioral therapy-informed physical therapy in FND.

Hypotheses: Improvement will correlate with increased volume, cortical thickness, and/or
white matter integrity in salience network-related regions post- versus pre- treatment.
Pre-treatment (baseline) salience network volume, cortical thickness, and/or white mater
integrity will predict clinical outcome of the 12-week treatment program.

Specific Aim 2:

SA2) Identify resting-state functional MRI biomarkers linked to and predictive of improvement
following cognitive behavioral therapy-informed physical therapy in FND.

Hypotheses: Improvement will correlate with reduced post- versus pre- treatment
salience-somatomotor network resting state functional connectivity, and pre-treatment
salience-somatomotor network functional connectivity strength will predict clinical outcome.

SA3) Identify baseline psychometric factors that correlate with clinical improvement (post
vs. pre-treatment), including differences among FND sub-populations and baseline predictors
of clinical improvement in FND.

Hypotheses: FND patients with more adaptive psychological profiles at baseline will be more
responsive to treatment.

Inclusion Criteria:

- FND patients will be recruited from the FND clinic and allied neurology and psychiatry
clinics at Massachusetts General Hospital, with additional recruitment occurring
through the physical therapy department. This study aims to recruit a total of 70
patients with motor FND. FND subjects will meet established clinical diagnostic
criteria and patients with functional weakness will be diagnosed by "positive" signs
suggestive of functional weakness including but not limited to a positive Hoover's
sign. Individuals with PNES who have a concurrent functional limb weakness and/or a
functional movement disorder will also be recruited. In addition, all individuals will
have a clinical indication for PT (i.e. limb weakness, gait difficulties, abnormal
movements).

Exclusion Criteria:

- Any significant major neurological disorder resulting in specific MRI abnormalities
(i.e. encephalomalacia, severe traumatic brain injury (TBI)), poorly controlled major
medical illness with known central nervous system consequences, inability to read
English, pregnancy, claustrophobia, or inability to satisfy MRI safety measures.
Additionally, patients with isolated PNES will not be considered for this study.

Note: individuals who are eligible for the study but have an MRI contraindication may be
offered study enrollment with MRI data collection for participation in aim 3 of this study.