Damage in thalamic projection to perilesional cortex as a prognostic biomarker for experimental post‐traumatic epilepsy

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OBJECTIVE: To test a hypothesis that a lesion in the optic tract, a thalamocortical pathway projecting from the thalamus to the perilesional cortex, is a prognostic biomarker for the development of post-traumatic epilepsy (PTE). METHODS: A lateral fluid-percussion injury (FPI)-induced traumatic brain injury (TBI) was induced in adult male Sprague-Dawley rats. The development of PTE was assessed from 1-month-long video-electroencephalography (EEG) data acquired during the seventh post-injury month. Diffusion magnetic resonance imaging (MRI) tractography of the optic radiation was performed using data acquired at 9 days and at 5 months post-injury. The optic tract in each hemisphere was divided into segments, and tract and diffusion tensor-based metrics were obtained for use as predictor variables (a total of 451 predictors). In the training cohort, including 17 TBI rats with (TBI+) and 66 without epilepsy (TBI-) at 9 days and 18 TBI+ and 69 TBI- rats at 5 months, 20 predictor variables with the highest effect sizes (Cohen's delta) were selected. These variables were used with elastic net-regularized logistic regression to model the development of PTE. The predictor variables chosen in the training cohort were also used for model fitting in a separate validation cohort (8 TBI+ and 23 TBI- at 9 days; 9 TBI+ and 23 TBI- at 5 months). RESULTS: In the training cohort, the fitted models explained the development of PTE with (cross-validated) areas under the receiver-operating characteristic (ROC) curve (AUC) of 0.74 (p = .003) at 9 days and 0.76 (p < .001) at 5 months post-TBI. Models fitted in the validation cohort achieved AUC values of 0.50 (p = 1) at 9 days and 0.77 (p = .03) at 5 months post-TBI. SIGNIFICANCE: Our data show that white matter pathology is involved in post-traumatic epileptogenesis after lateral FPI. Moreover, imaging of thalamocortical pathway(s) to perilesional cortex could identify translational prognostic biomarkers for post-traumatic epileptogenesis.