Abstracts

Rationale: A growing body of literature suggests that patients with seizure disorders are able to predict subsequent seizure occurrence shortly after an acute stress experience. However, few neuroimaging studies have investigated changes in neural function underlying stress reactivity in patients with seizure disorders. The objective of the current study was to compare the neural response to acute psychosocial stress in patients with left temporal lobe epilepsy (LTLE) and healthy controls (HC). Methods: 36 LTLE patients and 36 HCs completed a variant of control math task (CMT) and stress math task (SMT) conditions based on the Montreal imaging stress task (MIST). HCs did not differ significantly from LTLE patients in age, gender, years of education, perceived stress (PSS10; Cole, 1999), or depression (BDI, Beck et al., 1996). 27 LTLE patients reported that prior (acute) stress affected their seizures (LTLE S+); 9 did not (LTLE S-). LTLE S+ and LTLE S- groups did differ in seizure frequency within 3 months prior to data collection. Measures of stress reactivity included differential fMRI response to MIST conditions (SMT-CMT) and change in heart rate (HR; beats per minute, BPM) during MIST conditions (SMT-CMT). Results: Mean change in HR demonstrated that, regardless of group, the MIST elicited a significant increase between CMT and SMT conditions [M diff= 6.97 BPM, t(68)=4.997, p<0.001]. A linear mixed effects analysis [3dLME in AFNI (Cox, 1999)] compared the the neural response to stress (SMT-CMT) to perceived stress as a function of LTLE and HC groups. The results of this analysis revealed that the relationship between the neural response to stress and perceived stress varied between LTLE patients and HCs within the hippocampal complex (parahippocampal gyrus and hippocampus). Specifically, the analysis revealed two clusters within the anterior (108 mm³) and posterior (135 mm³) right hippocampal complex (p<0.001 uncorrected, p<0.05 corrected). As a follow up analysis, a signal extraction was performed on the two right hippocampal clusters to assess whether the linear relationship between the neural response to stress and perceived stress differed as a function of LTLE S+, LTLE S- and HC groups. The results of this follow-up analysis revealed that as perceived stress increased, negative differential activation in in right posterior hippocampal complex increased for the LTLE S+ group (r=-0.628, p<0.005), but not for the LTLE S- or HC groups (both ps>0.20).  Conclusions: Negative differential activation in the hippocampal regions serves as a disinhibitory neural mechanism, triggering HPA axis activation and the release of cortisol in response to stress (Dedovic et al., 2009; Goodman et al., 2016; Pruessner et al., 2008; Khalili-Mahani et al., 2010). The result of the current study provides a potential neural mechanism underlying differences in the response to stress between HCs and LTLE, as well as LTLE patients that report stress as a precipitant of seizures. Funding: Study support was provided by the Charles Shor Foundation for Epilepsy Research (to JPS and JBA).