Neuroimaging biomarkers for sense of control, catastrophic expectations, and stress reactivity as novel treatment targets for functional seizures.

University Of Alabama At Birmingham, Birmingham AL

Investigators

Abstract

Project Summary/Abstract Functional seizures (FS) are a subtype of Functional Neurological Disorder (FND). FS are paroxysmal attacks resembling epileptic seizures, but without corresponding epileptiform activity in the brain. They account for at least 20% of new epilepsy evaluations and negatively affect independence, employability, and caregiver wellbeing. FND as a whole cost the U.S. healthcare system $1.2 billion annually. Despite their significant prevalence and burden, there are no validated treatments for FS. Research has suggested that sense of control over physical symptoms, catastrophic symptom expectations, and stress reactivity may be possible novel treatment targets for reducing FS. Sense of control is the extent to which a person perceives they are in control, and is impaired in patients with FS because symptoms are perceived as involuntary. Catastrophic symptom expectations are expressed as both a tendency to interpret normal physical sensations as threatening (i.e., indicating disease) and a tendency to over-estimate the likelihood that threatening symptoms will occur, which can themselves induce the feared symptoms. Heightened stress reactivity stems from defective emotion regulation abilities and confers vulnerability for several mental health conditions, including FS. Objective outcome measures for these endpoints have not been established in this population, which limits our ability to assess the effectiveness of FS interventions. Thus, the proposed project aims to develop objective neuroimaging-based outcome measures for the above targets. We will use functional magnetic resonance imaging (fMRI) to examine neural activity in brain regions associated with emotion processing and control, including the prefrontal cortex, cingulate, insula, hippocampus, and amygdala. Forty adults with FS and 40 controls matched on age, sex, and Psychiatric comorbidities will undergo fMRI while completing two tasks: the Threat Predictability and Controllability Task (TPCT) will assess neural responses to controllable vs. uncontrollable and predictable vs. unpredictable threats, and the Montreal Imaging Stress Task (MIST) will measure neural responses to performance demand stress (induced via challenging mental arithmetic) and social evaluative stress (induced via negative auditory feedback). We will also collect expectancy ratings prior to threat presentation on the TPCT to assess potential biases in threat anticipation in FS compared to controls. Uncovering the neural substrates of abnormal behavior in FS will enhance our understanding of FS pathophysiology and provide critical tools to improve interventions for this condition. This Mentored Career Development Award will provide opportunities to acquire skills in fMRI experimental design, data acquisition, and analysis; acquire knowledge of conditioning paradigms relevant to FS development and treatment; and participate in career development activities including grant writing, lab management, and networking. The award will allow me to transition my research program to the field of FND and meet my long-term career goal of becoming an independent investigator.