Postdoctoral Fellow University of Alabama at Birmingham Birmingham, Alabama
Rationale: Psychogenic nonepileptic seizures (PNES) are associated with psychosocial stressors. Delay in PNES diagnosis and treatment may be a predictor of comorbidity and seizure outcomes, yet limited prior studies have examined changes in neurobiological functioning that underlie healthy emotional processes. We examined associations of time lag effects between early and delayed diagnoses on the neural response to stress in order to investigate the impact of PNES diagnosis delay on the neural response to stress. Methods: Forty-two volunteers with video EEG confirmed PNES and a history of TBI completed a control math task (CMT) and stress math task (SMT) during functional magnetic resonance imaging (fMRI) using a 3T Siemens Prisma scanner. Using the factor of time lag between PNES onset and diagnosis (days), a median split divided participants into 1) Early and 2) Delayed diagnosis groups. fMRI data were analyzed in AFNI (NIH.gov). Linear mixed-effects models (3dLME) compared linear effects of time lag (days) on neural responses to stress between Early and Delayed groups. A corrected volume threshold (corrected p< 0.05) was determined by Monte Carlo simulations (3dClustSim) for a priori regions of interest (Harvard-Oxford MNI atlas) based on previous studies of neural responses to stress Results: The Delayed group (M= 2917 days, SD= 3811) and Early group (M= 214 days, SD= 169) were separated by a median delay of approximately 17 months (cut-off value= 507 days) between PNES onset and diagnosis. 3dLMEs revealed a cluster in which time lag effects on neural responses to stressful math performance (SMT > CMT) differed between groups within the right insula region (447 mm3). Likewise, time lag effects on responses to negative evaluative feedback (SMT > CMT) differed between groups in dorsal anterior cingulate cortex (621 mm3, 293 mm3), superior frontal gyrus (406 mm3), ventral anterior cingulate cortex (320 mm3) and right hippocampal complex (94 mm3) regions. All remaining clusters of interactions failed to reach the volume threshold criteria. Conclusions: Delay in PNES diagnosis can result in inappropriate treatment, increased risk of injury, morbidity, and poor quality of life. In the current study, we found associations between hippocampal and prefrontal cortex (PFC) reactivity and PNES onset to diagnosis time lag, in which inter-individual stress responses vary as a function of delay in diagnosis between those who are diagnosed early vs. those with delayed diagnosis. These results extend prior findings of aberrant hippocampal and PFC responses to stress in PNES by potentially implicating these alterations as a possible link between diagnostic delays and disruption in healthy emotional processes. Future prospective studies could assess the relationship between delay of treatment, comorbidity, and treatment responses. Funding: Please list any funding that was received in support of this abstract.: This work was supported by the U.S. Department of Defense (W81XH-17-0619)
