Abstracts

Rationale: Altered brain responses to emotional stimuli have been shown in adults with functional seizures (FS) compared to controls. Delayed time to FS diagnosis (TTD) negatively impacts patient outcomes and quality of life. TTD may contribute to an altered response, particularly in emotion network regions of interest (bilateral prefrontal cortex, cingulate, insula, amygdala, hippocampus and parahippocampal gyrus). We investigated the impact of TTD on emotion processing during an fMRI emotion faces task (EFT). We hypothesized TTD would be associated with differential fMRI activation in brain regions involved in emotion processing during the EFT.

Methods: Adults with video-EEG confirmed FS after traumatic brain injury (n=52; 38 females) were recruited from the University of Alabama at Birmingham and Rhode Island Hospital. Subjects completed assessments related to symptoms of depression (BDI-II), anxiety (BAI), and post-traumatic stress disorder (PCL-S), and the EFT during fMRI acquisition on 3T Prisma scanners. During fMRI subjects indicated “male” or “female” via button press while viewing a series of happy, sad, fearful and neutral faces. FMRI response to each emotion was modeled and group analyses were performed in AFNI. A median split (507 days) defined short- (sdTTD) and long-delay (ldTTD) groups. FMRI signal was extracted from clusters showing group differences, and Spearman’s correlations assessed relationships with symptom scores.

Results: Groups did not differ in onset age of FS, sex distribution, years of education, or scores on the BDI-II, BAI and PCL-S. The sdTTD group was younger than ldTTD (mean age 32.6 vs. 40.1; p=0.022). The ldTTD group showed greater fMRI activation than sdTTD to sad faces in the bilateral posterior cingulate cortex (PCC; 424 mm³; t=4.76; peak MNI coordinates at x=-2, y=-43, z=-18) and to neutral faces in the right anterior insula (374 mm³; t=5.10; peak MNI coordinates at x=31, y=20, z=-12). Activation differences were corrected at p< 0.05 (voxelwise p=0.005, cluster >298 mm³ for neutral faces and cluster >292 mm³ for sad faces) as determined by Monte Carlo simulations. There were positive correlations between PCC response to sad faces and BDI-II scores in the ldTTD group (rho=0.50, p=0.011) and the combined sample (rho=0.31, p=0.025). The sdTTD group showed a non-significant trend for a negative correlation between PCC response to sad faces and PCL-S scores (rho=-0.31, p=0.12).

Conclusions: In this study, those with more time between symptom onset and FS diagnosis ( >16 months) showed greater engagement of the insula and PCC during an fMRI emotion processing task. Interestingly, increased PCC activation to sad faces in those with a long delay in FS diagnosis was associated with worse symptoms of depression (i.e. higher BDI-II score) and is likely driving the similar association also observed in the combined sample. Connected to default mode network activity, the PCC is implicated in depression, self-referencing, and other emotion-relevant processes. These findings point to specific emotion processing mechanisms that may be impacted by diagnosis delays.

Funding: Please list any funding that was received in support of this abstract.: This work was supported by the US Department of Defense (W81XH-17-0619) to WCL and JPS.