Abstracts

Rationale: Psychogenic nonepileptic (functional) seizures (FS), a type of functional neurological symptom disorder (FNSD), are associated with psychological stressors. Further, traumatic brain injury (TBI) is a significant risk factor for FS outcomes. The amygdala, hippocampus, and medial prefrontal cortex are connected by a white matter pathway, known as the uncinate fasciculus (UF), and form a limbic brain network implicated in emotion regulation and psychopathology. Prior evidence suggests rightward asymmetry of UF connectivity in FS may play a role in psychiatric comorbidities and aberrant emotion processing. In the current study, we assess UF connectivity and relationships with psychiatric symptom severity in FS using diffusion MRI (dMRI) and TBI as a model.

Methods: Participants with a history of TBI and video-EEG confirmed FS (FS+TBI; n=36) and no history of seizures (TBI-only; n=34) were recruited from the University of Alabama at Birmingham (UAB) and Rhode Island Hospital. Participants completed a series of questionnaires and a dMRI scan (99-direction sequence) in Siemens 3T Prisma scanners using a 64-channel head coil. DMRI data were analyzed in DSI studio with q-space diffeomorphic reconstruction (QSDR) followed by streamline production and manual segmentation of the uncinate fasciculi bilaterally. Normalized quantitative anisotropy (nqa) measures (range: 0-1), which are more robust to crossing fibers compared to traditional fractional anisotropy measures, served as an estimate of white matter integrity (WMI).

Results: Measures of nqa and number of streamlines calculated for each hemisphere were compared between the FS+TBI and TBI-only groups using independent samples t-tests. The results revealed significantly increased nqa in the right UF for the FS+TBI group compared to the TBI-only group (p=0.035) with no significant between-group differences for the left UF (p=0.07). The FS+TBI and TBI-only groups did not differ significantly in the number of UF streamlines for the right (p=0.18) or the left (p=0.73). Planned follow-up analyses examined associations between the right UF nqa measures and psychiatric symptoms of depression (BDI-II), anxiety (BAI), and PCL-S (PTSD) separately for each group using Spearman rank bivariate correlation tests, to reduce any potential influence of outliers. For the FS+TBI group, correlation tests revealed that as right UF nqa values decreased, measures on the BDI-II (p=0.005) and PCL-S (p=0.003) increased. Remaining tests comparing BAI to right UF nqa failed to reach the criteria for significance. For the TBI-only group, right UF nqa was not significantly correlated with BDI-II, BAI, or PCL-S measures.

Conclusions: Consistent with prior work, patients with FS+TBI compared to TBI-only demonstrated increased WMI in the right, but not left UF. Right UF WMI diffusion indices correlated negatively with mood and PTSD symptom severity only in the FS+TBI group. These findings lend support that FS are linked to increased right UF WMI, while providing novel evidence that these changes may be related to comorbid psychiatric symptoms.

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) to WCL and JPS.