Research Assistant University of Alabama at Birmingham
Rationale: Psychogenic nonepileptic seizures (PNES) have been proposed as a network brain disorder. Expression of comorbid psychiatric symptoms in PNES following traumatic brain injury (TBI) may depend on how brain regions that comprise the putative PNES network are affected. Multimodal evidence suggests that connectivity between salience network (dorsomedial PFC [dmPFC], insula) and motor cortex (precentral gyrus) regions are altered in PNES. In the current study, we assess functional connectivity between these nodal regions, and relationships to psychiatric comorbidities in a well-characterized PNES sample. Methods: Participants with PNES and a history of TBI (n= 41; TBI+PNES) and TBI without PNES (n= 46; TBI-only) were recruited from both The University of Alabama at Birmingham (UAB) and Rhode Island Hospital. Participants completed a series of psychiatric symptom questionnaires prior to resting state functional magnetic resonance imaging (rs-fMRI). Questionnaires included the BDI-II (depression), BAI (anxiety), PCL-S (PTSD), and SCL-90-R (symptom checklist). Rs-fMRI data were submitted to standard preprocessing and denoising before an ROI seed-based analysis identified connectivity with dmPFC (MNI:0,20,39) and bilateral insula (MNI:44,6,2; -43,6,4) 5mm radius sphere nodes (Raichle, 2011). Results: TBI+PNES sample reported greater symptom severity for all questionnaires (all ts > 2.1, ps< 0.05) and most SCL-90-R sub-scales. Linear mixed effects analysis identified voxel-wise connectivity differences between groups, controlling for factors of MRI site, age, and sex. To reduce family-wise error (FWE) rates, comparisons were restricted within dmPFC, bilateral insula, and precentral gyrus regions (Harvard-Oxford MNI atlas) and submitted to cluster volume threshold correction (p< 0.01 uncorrected; α< 0.05, corrected). For TBI+PNES, connectivity was increased between the left insula seed and a cluster within the dmPFC (384 mm3), but was decreased between the dmPFC seed and right precentral gyrus (608 mm3). Mean connectivity for surviving clusters was compared to psychiatric symptom severity using Spearman rank correlations (false discovery rate (FDR) corrected). Connectivity between the dmPFC seed and precentral gyrus cluster were inversely correlated with BDI-II, BAI, PCL-S, and SCL-90-R (somatization, obsessive compulsive, depression, phobic anxiety, global severity) values, all rs< -0.28 (p< 0.05; FDR). Connectivity between the left insula seed and dmPFC cluster was positively correlated with SCL-90-R somatization values, rs= 0.31 (p< 0.05; FDR). Conclusions: TBI+PNES demonstrated decreased connectivity between control (dmPFC) and motor (precentral gyrus) regions that was correlated with widespread mood, anxiety, and somatization symptom severity, while increased connectivity between emotion (insula) and control (dmPFC) regions was correlated only with somatization. These findings identify motor and emotion control network disruptions that may reflect mood, anxiety and somatic symptoms expression in PNES. 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)
