Abstracts

Rationale: Psychosocial stress is thought to be a major factor in the development and persistence of psychogenic non-epileptic seizures (PNES). Our objective was to assess the relationships between the functional magnetic resonance (fMRI) response to psychosocial stress and functional connectivity of stress-related brain regions with quality of life (QOL) in patients with PNES.Methods: 17 subjects (9 PNES) were enrolled. 8 female patients with PNES and 7 age-/sex-matched healthy control subjects (HCs) performed a stress induction paradigm during fMRI, which consisted of control (CMT) and stress math (SMT) tasks in which they received auditory positive (non-stressful) and negative (stressful) feedback, respectively. 9 patients with PNES (1 male) and 8 HCs (2 male) underwent resting state fMRI (RS-fMRI). All subjects were administered the Beck Depression Inventory II (BDI-II) to assess severity of recent depressive symptoms, and the SF-36 to assess quality of life. Group difference in psychosocial stress reactivity was measured using the fMRI response to SMT negative feedback, while controlling for BDI-II scores. Regression analysis examined the relationship between fMRI response to negative feedback and QOL in patients with PNES, while also controlling for BDI-II scores; regions that showed significant associations were used as seed regions in RS-fMRI analysis.Results: BDI-II and SF-36 scores were significantly worse for patients with PNES compared to HCs (both p<0.01). Patients with PNES exhibited increased fMRI stress reactivity compared to HCs in a number of regions including the middle frontal gyrus bilaterally, left caudate extending into the anterior cingulate cortex, bilateral medial and superior frontal gyrus, and left inferior frontal gyrus (Fig. 1). We observed decreased activation in the right fusiform gyrus in patients with PNES compared to HCs (Fig. 1). Regression analysis showed a positive association between QOL in patients with PNES and fMRI stress reactivity in the bilateral angular gyrus and paracentral lobule, as well as a negative association with activation in the bilateral insula and left inferior frontal gyrus (Fig. 2). Compared to HCs, patients with PNES showed increased RS-fMRI connectivity from the left and right insula, left inferior frontal gyrus, paracentral lobule, and left angular gyrus to other brain regions. Decreased RS-fMRI connectivity from the left and right angular gyrus to other brain regions was also found for patients with PNES compared to HCs.Conclusions: Increased fMRI reactivity to psychosocial stress in frontal/prefrontal brain regions may be a factor in the poor QOL of patients with PNES given the observed negative associations between frontal/prefrontal activations and QOL. This is further supported by the increased RS-fMRI connectivity for patients with PNES compared to HCs in these frontal/prefrontal regions.