Abstracts

Rationale: Electrical stimulation of the thalamus can reduce seizure frequency in temporal lobe epilepsy (TLE), indicating thalamic connectivity to regions in the epileptic network. Another treatment is resecting brain regions that generate/propagate seizures, such as sections of the amygdala, hippocampus, lesions, and encephalocele. The white matter tracts connecting the thalamus to the rest of the brain are estimated noninvasively with diffusion-weighted MRI (DWI). Previous TLE studies show large-scale brain network alterations before surgery. Here we aim to investigate changes in structural connectivity (SC) of thalamic subregions for TLE patients before and after selective amygdalohippocampectomy (SAH) surgery.


Methods: This study included 36 TLE patients (22 right, mean age 41 years, 23 males) and 85 healthy controls (mean age 38 years, 45 males). Patients underwent a T1-weighted scan (1x1x1 mm3) and DWI (2.5x2.5x2.5 mm3, 92 directions, b = 1600 s/mm2) on a 3T MRI scanner before and after (mean 33 months) undergoing SAH. Controls were scanned once. 115 cortical and subcortical regions of interest and 12 thalamic subregions (Fig 1a) were segmented from the scan.¹

Spherical deconvolution estimated fiber orientation distributions from DWI data. The thalamus was seeded for probabilistic tractography with a minimum streamline length of 20 mm and 2500 streamlines per voxel (Fig1b,c). SC was the number of streamlines between each thalamic subregion and all brain regions weighted by streamline length and inverse region size to obtain a 12 x 127 structural connectome for each participant. A linear fit with age across the controls transformed SC to units of standard deviations from age matched control. Left TLE patients were flipped using ipsilateral (I) and contralateral (C) to resection.

A paired t-test comparing the SC of pre to post and a two-sample t-test comparing the pre surgery to controls was performed at each connection not surgically removed. Significance was corrected for multiple comparisons.




Results: Our results show 22 of 1502 thalamic connections differed after surgery (p < 3.3 x 10-5; Fig 2a). All thalamic subregions had at least one connection altered. I Central Median Lateral (CML), bilateral pulvinar (Pul), I Temporal Pole (TP) and C Posterior Hippocampus (PH) were the most prevalent. I TP and C PH connections’ SC increased while the other connections’ SC decreased after surgery. Two of these connections, I Pul to I TP and I LDP to I TP, were less than controls before surgery but increased toward controls after surgery (Fig 2b,c).


Conclusions: Here we found changes in TLE thalamic structural connectivity after SAH. Notably, two thalamic connections normalized toward healthy controls after surgery, while other postsurgical changes were connections not affected by epilepsy prior to surgery. It is currently unclear how these relate to seizure outcome. These findings could enhance understanding of the role of the thalamus in TLE, potentially leading to more effective thalamic neurostimulation targets.



Reference:

1. Liu et al., Magn Res Imaging 2020; 65, 114-128.




Funding: Funded by NIH T32 EB021937, R01 NS075270, R01 NS108445, R01 NS110130, and R00 NS097618.