Abstracts

Rationale: Psychogenic nonepileptic seizures (PNES) are a conversion disorder (CD) that can occur following a traumatic brain injury (TBI) and that are linked to poor mental health (MH). As emotional processing is also altered by trauma and is frequently thought to be the precipitating event, TBI may serve as an optimal model for studying MH in PNES. Emotional stressors and poor MH are common in PNES, however, the associated underlying neural mechanisms remain unclear. Healthy physiologic prefrontal cortex (PFC) and medial temporal regions decrease in response to psychosocial stress, triggering the HPA-axis. We hypothesized that differences in function within these regions during a psychosocial stress task observed in TBI+PNES compared to TBI only would correspond to changes in MH. Methods: Eighteen participants with a history of TBI+PNES and 31 participants with a history of TBI only completed control math task (CMT) and stress math task (SMT) conditions based on the Montreal Imaging Stress Task (MIST) during fMRI. Positive and negative auditory feedback during CMT and SMT, respectively, was provided irrespective of performance. Two Siemens Prisma MRI scanners at Brown University and the University of Alabama at Birmingham acquired fMRI data (same scanning parameters). MH assessments were administered to index mood (BDI-II), anxiety (BAI), and post-traumatic stress disorder symptoms (PCL-5). FMRI data were all submitted to standard processing in AFNI. FMRI signals from brain regions showing group differences were extracted and compared to BDI-II, BAI, and PCL-5. Results: Based on prior work, three cluster volume extent thresholds were calculated to correct for multiple comparisons using 3dclustsim (with -acf option) for an initial whole-brain mask (482.4 mm3) and for two small volume masks (Harvard-Oxford MNI atlas) in the left and right hippocampi and parahippocampal gyri (left=104.8 mm3; right=104.6 mm3). The 3dLME analysis revealed an interaction between Group (TBI+PNES vs TBI) and differential fMRI response to Conditions (SMT vs. CMT) during math performance within the left anterior cingulate (ACC; 549 mm3; MNI peak voxel: x= -10, y=33, z= -7). Signal extraction (3dROIstats) for the ACC cluster revealed an effect of Task (SMT vs. CMT) for TBI, but not TBI+PNES during math performance. During auditory feedback events, the second 3dLME analysis revealed an interaction within the left hippocampal region (165 mm3; MNI peak voxel: x=-24, y=-31, z=-8) that survived the small volume-corrected mask. Signal extraction for the hippocampal cluster revealed that there was an effect of Task for TBI+PNES but not TBI during auditory feedback.TBI+PNES group reported higher values on BDI (t(44)=2.44), BAI (t(44)=4.87), and PCL-5 scales (t(44)=2.71), (all p<0.05). Comparisons of these clinical assessments to signal extractions revealed that the ACC response to negative auditory feedback during the SMT was negatively correlated with BAI and PCL-5 (both rs<-0.35, ps<0.05), while the hippocampal response to math events during the CMT was negatively correlated with BDI-II, BAI, and PCL-5 (all rs<-0.43, ps<0.01). Conclusions: Physiologic responses to stressors decrease in hippocampal and ACC regions with the hippocampus disinhibiting mechanism triggering the HPA-axis. The current study identified differences in neural mechanisms underlying emotional processing in TBI compared to TBI+PNES. Further, relationships between neural responses to stress and clinical measures point to pathophysiologic mechanisms linking emotional stress and decreased MH states in PNES. Funding: This work was supported by the US Department of Defense (W81XH-17-0619).