White matter resection and verbal memory deficits after temporal lobe epilepsy surgery

Temporal lobe resection for focal, drug-resistant temporal lobe epilepsy (TLE) causes verbal memory deficits in 30% of left hemisphere-operated patients. Structural, functional and computational modelling have shown a widespread structural and functional memory network with hubs in critical brain regions including the hippocampus, subcortical and neocortical regions. We hypothesized that damage to white matter pathways forming a network involving cortical and subcortical regions may be responsible for postoperative memory problems. In this study, we measured verbal memory encoding (immediate recall) and retrieval (delayed recall) outcome at three timepoints (preoperative, 3- and 12-month postoperatively) in 146 left TLE patients who underwent temporal lobe surgery and evaluated the impact of white matter tract section on verbal memory. Outcome was measured by the change in scores from preoperative to 3- and 12-month postoperatively and via the reliable change index. Utilizing resection masks from pre- and postoperative T1 scans, an atlas-based analysis utilizing reconstructions of the ventral cingulum and fornix confirmed these tracts involvement in verbal encoding but not retrieval. Using preoperative diffusion MRI (dMRI) reconstructions with resection masks to estimate the percentage of fibre bundle transection, we found that the ventral cingulum was significantly related to verbal encoding change and the fornix was related to verbal retrieval across both 3- and 12-month timepoints. Investigating volumes of ventral cingulum and fornix from postoperative dMRI reconstruction revealed that greater volume remaining of the ventral cingulum and fornix was related to less decline in verbal encoding but not retrieval. Our results suggest that verbal encoding may be supported by direct and indirect connections between the medial temporal lobe and subcortical regions with memory deficits arising from their transection. Verbal retrieval may rely on a greater neocortical network. These findings may inform a revised surgical approach to minimize damage to the fornix and ventral cingulum to optimize memory outcome, but recognizing the potential for worse seizure outcome with less ventral cingulum resections.