Abstracts

Rationale: Personality and psychiatric disorders are often experienced by individuals with Temporal Lobe Epilepsy (TLE). Neuroticism, a tendency towards experiencing negative feelings, is higher in TLE than healthy individuals. Previous research has shown an association between neuroticism and altered brain volume in both healthy individuals (Gray et al. 2010; Lu et al. 2014), and TLE patients (Rivera-Bonet et al., under review). However, functional brain connectivity in TLE in relation to neuroticism remains unknown. In this study, we used resting state functional Magnetic Resonance Imaging (rs-fMRI) to identify differences in resting functional connectivity patterns between controls and TLE patients.Neuroticism is a known predictor of depression (Dunkley et al. 2009), which TLE patients also experience in higher rates (Saha et al. 2017). To further understand this relationship, we did the same analysis using depression scores. Methods: All data were from the Epilepsy Connectome Project. Rs-fMRI images (TR=0.8s, 2.0mm isotropic) were acquired for 20 minutes with 3T GE scanners using simultaneous multi-slice imaging, and processed using the Human Connectome Project pipelines (Glasser et al., 2013). Images were bandpass filtered (0.01-0.1Hz) and white matter, cerebrospinal fluid, global signal, and motion vectors were regressed out. Glasser Parcellation (Glasser et al., 2016) and FreeSurfer subcortical regions (Fischl et al., 2002) were extracted. Pearson correlation was used to generate connectivity matrices.Neuroticism scores were obtained using the NEO-Five Factor Inventory. Images of 45 TLE patients with high neuroticism scores (38.3±12.1years, scores=31.5±5.1), 44 with low (38.4±11.0years, scores=14.1±5.2), and 28 healthy controls (34.8±11.6years, scores=16.1±8.2) were compared. Adult Self-Report Achenbach was used to measure depression. Standardized T scores were calculated. Images of 43 TLE patients with high depression scores (37.2±10.8years, scores=67.4±7.3), 43 with low (37.0±10.4years, scores=51.3±1.7), and 40 healthy controls (33.9±10.2years, scores=54.5±6.5) were compared. Benjamini-Hochberg was used for multiple comparison corrections with p=0.05.Analyses of variance (ANOVA) were performed to screen out insignificant features, then two-group t-tests to confirm differences between the two median-split TLE groups. Results: TLE patients showed higher neuroticism (p<0.001) and depression (p=0.001) scores compared to controls. Neuroticism and depression scores were significantly correlated, both in TLE patients (r=0.71, N=114) and controls (r=0.63, N=35).In neuroticism, 11 connections showed significant changes (p<0.05), of which 9 were weaker in TLE patients with high neuroticism. 4 of these 9 were right hippocampal connections . In depression, 8 connections showed significant changes (p<0.05), of which 7 were weaker in TLE patients with high depression. 4 of these 7 were right hippocampal connections. Hypo-connectivity between right hippocampus to right area 47m (inferior frontal gyrus) was common to both. Conclusions: Past theory suggested that changes in personality and behavior in TLE were associated with hyper-connectivity between limbic and diverse cortical areas (Bear, 1979), a theory that has never been empirically tested. The present findings support a pattern of altered connectivity, but hypo- as opposed to hyperconnectivity, between mesial temporal and cortical regions with prominence of hypoconnectivity between hippocampus and frontal lobe regions with increased neuroticism and depression. Funding: U01NS093650T32MH018931