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 (Perez et al. Cogn Behav Neurol 2016; Matin & Perez et al. J Neuropsychiatry Clin Neurosci 2017). 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 (Perez et al. J Neuropsychiatry Clin Neurosci 2012, 2015, Clin EEG Neurosci 2015). 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. A particular focus of this grant application is the specific hypothesis that FND symptoms relate to structural and functional alterations within the salience network, which includes the anterior insula, anterior cingulate cortex, dorsal amygdala and periaqueductal gray. The overall goal of this proposal is to comprehensively investigate structural and functional MRI biomarkers of symptom severity, adverse life event burden (a FND risk factor) and prognosis across motor FND. Across aims 1-3 of this proposal, multimodal structural and functional magnetic resonance imaging (MRI) techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) are used to systemically probe brain-symptom severity, brain-trauma burden and brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach and Dr. Perez's training in the full complement of structural and resting state functional MRI techniques. This project leverages the candidate's past fMRI experience probing brain-symptom relationships in other neuropsychiatric disorders (Perez et al. Psychiatry Res 2015; Psychiatry Clin Neurosci 2016), as well as Dr. Perez's recently published MRI study probing gray matter volume associations with self-report measures of symptom severity and childhood abuse burden in patients with motor FND (Perez et al. J Neurol Neurosurg Psychiatry 2017). Pilot data for all 3 aims is presented in this proposal. These studies in motor FND will identify trans-diagnostic neural biomarkers linked to symptom severity, adverse life events and prognosis. The results of this project will catalyze future comprehensive prognostic and treatment research including the potential future study of targeted neuromodulation and treatment response biomarkers based on baseline neuroimaging profiles.

Public Health Relevance

Motor Functional Neurological Disorder (a.k.a. Conversion Disorder) is a highly prevalent and disabling neuropsychiatric disorder, comprising 16% of outpatient neurology referrals. This condition includes patients with Nonepileptic Seizures, Functional Movement Disorders and Functional Limb Weakness. Motor Functional Neurological Disorder and other medically unexplained psychogenic conditions are exceedingly costly to the U.S. health care system, with an estimated $256 billion/year spent in caring for this population. This project seeks to comprehensively identify neuroimaging biomarkers of symptom severity, adverse life event burden (a disease risk factor), and prognosis across the spectrum of motor Functional Neurological Disorders, with the aim of advancing our neuropathophysiologic understanding of this condition and subsequently catalyzing the development of biologically informed treatment studies.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Chavez, Mark
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Massachusetts General Hospital
United States
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Perez, David L; Keshavan, Matcheri S; Scharf, Jeremiah M et al. (2018) Bridging the Great Divide: What Can Neurology Learn From Psychiatry? J Neuropsychiatry Clin Neurosci :appineuropsych17100200
Williams, Benjamin; Jalilianhasanpour, Rozita; Matin, Nassim et al. (2018) Individual differences in corticolimbic structural profiles linked to insecure attachment and coping styles in motor functional neurological disorders. J Psychiatr Res 102:230-237
Jalilianhasanpour, Rozita; Williams, Benjamin; Gilman, Isabelle et al. (2018) Resilience linked to personality dimensions, alexithymia and affective symptoms in motor functional neurological disorders. J Psychosom Res 107:55-61
Williams, Benjamin; Ospina, Juan Pablo; Jalilianhasanpour, Rozita et al. (2018) Fearful Attachment Linked to Childhood Abuse, Alexithymia, and Depression in Motor Functional Neurological Disorders. J Neuropsychiatry Clin Neurosci :appineuropsych18040095
Ranford, Jessica; Perez, David L; MacLean, Julie (2018) Additional occupational therapy considerations for functional neurological disorders: a potential role for sensory processing. CNS Spectr 23:194-195
Perez, David L; Matin, Nassim; Williams, Benjamin et al. (2018) Cortical thickness alterations linked to somatoform and psychological dissociation in functional neurological disorders. Hum Brain Mapp 39:428-439
Peterson, Krystyna T; Kosior, Robert; Meek, Benjamin P et al. (2018) Right Temporoparietal Junction Transcranial Magnetic Stimulation in the Treatment of Psychogenic Nonepileptic Seizures: A Case Series. Psychosomatics 59:601-606
Perez, David L; Williams, Benjamin; Matin, Nassim et al. (2018) Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study. J Neurol Neurosurg Psychiatry 89:1221-1224
Pick, Susannah; Goldstein, Laura H; Perez, David L et al. (2018) Emotional processing in functional neurological disorder: a review, biopsychosocial model and research agenda. J Neurol Neurosurg Psychiatry :