Abstracts

Rationale: Drug-resistant temporal lobe epilepsy (TLE) in adults commonly includes a pathology of hippocampal sclerosis (HS), neuronal loss and gliosis that can also extend into the amygdala. However, TLE involves impairment of brain regions and networks beyond the seizure focus. The purpose of this study was to investigate the impact of pathology on network-wide brain dynamics in presurgical TLE patients, using networks derived from diffusion-weighted imaging (DWI) and average regional controllability (ARC) which is a measure to determine a region’s influence on brain state dynamics.

Methods: Presurgical 3T DWI, 2.5x2.5x2.5 mm³, 92 directions, and b-value = 1600 s/mm² was acquired in 52 TLE (16 left TLE, 42 HS, clinically confirmed unilateral) patients and 95 healthy controls. A T1W3D scan, 1x1x1 mm³ resolution, was used to perform an automated brain parcellation of 117 cortical and subcortical regions of interest. TLE patients were separated into two groups: (1) Pathology confirmed HS, and (2) either partial gliosis or normal pathology. A structural connectome (SC) was generated using whole-brain tractography with strength defined as the weighted number of streamlines between each region pair (Figure 1). ARC, a measure of the ability for each brain region to steer the network into different states with little effort [1], was computed for each region in every subject. Unpaired t-tests were performed with ARC for each region and a total z-score of absolute distance from controls was computed in each hemisphere for the two cohorts.

Results: TLE patients with HS showed reduced ARC in the ipsilateral posterior hippocampus and the parahippocampal gyrus compared to healthy controls (p < 0.05, adjusted α = 0.05/117), Figure 2A. No regional differences survived multiple comparisons for the TLE cohort without HS. Total ARC deviations from controls were higher ipsilateral compared to contralateral in TLE-HS (p = 0.002), Figure 2B.

Conclusions: Local ipsilateral reductions in ARC were found around the seizure focus within the posterior hippocampus and the parahippocampal gyrus. TLE-HS also showed global increased total ARC deviations from controls across the ipsilateral hemisphere. Patients without HS did not show local deviations around the seizure focus nor total ARC deviation between hemispheres. This study suggests that hippocampal pathology in the seizure focus has both local and global effects on how brain regions coordinate brain state dynamics.

References
[1] Gu, S., Pasqualetti, F., Cieslak, M., Telesford, Q. K., Yu, A. B., Kahn, A. E., Medaglia, J. D., Vettel, J. M., Miller, M. B., Grafton, S. T., & Bassett, D. S. Controllability of structural brain networks. 2015. Nat. Commun, 6.

Funding: Please list any funding that was received in support of this abstract.: Funded by NIH NS075270, NS110130, NS108445, R00 NS097618, and T32 EB001628.