Precentral gyrus and insula responses to stress vary with duration to diagnosis in functional seizures

Objective This study was undertaken to determine whether undiagnosed illness duration (time between functional seizures [FS] onset and diagnosis) is linked to differences in neural response and functional connectivity during processing of stressful experiences. Methods Forty-nine participants with traumatic brain injury preceding the onset of FS confirmed by video-electroencephalography were recruited prospectively. Participants completed psychiatric symptom assessments before undergoing functional magnetic resonance imaging (fMRI) with an acute psychosocial stress task. Linear mixed effects (LME) analyses identified significant interactions between the factors of group (early vs. delayed diagnosis) and time lag to diagnosis on neural responses to stressful math performance and auditory feedback (corrected alpha = .05). Functional connectivity analysis utilized clusters from initial LME analyses as seed regions to determine significant interactions between these factors on network functional connectivity. Results Demographic and psychiatric symptom measures were similar between early (n = 25) and delayed (n = 24) groups. Responses to stressful math performance within the left anterior insula and functional connectivity between the anterior insula seed region and a precentral gyrus cluster were significantly negatively correlated with time lag to diagnosis for the early but not the delayed FS diagnosis group. There was no correlation between fMRI findings and psychiatric symptoms. Significance This study indicates that aberrant left anterior insula activation and its functional connectivity to the precentral gyrus underlie differences in processing of stressful experiences in patients with delayed FS diagnosis. Follow-up comparisons suggest changes are associated with undiagnosed illness duration rather than psychiatric comorbidities and indicate a potential mechanistic association between neuropathophysiology, response to stressful experiences, and functional neuroanatomy in FS.

Automated summary

This study found that patients with delayed diagnosis of functional seizures had differences in neural activation and functional connectivity during processing of stressful experiences compared to those with early diagnosis. These differences were correlated with the duration of undiagnosed illness and not with psychiatric comorbidities. The findings suggest a potential mechanistic association between neuropathophysiology, response to stressful experiences, and functional neuroanatomy in functional seizures.