Post‐traumatic epilepsy (PTE) is a debilitating neurological disorder that develops after traumatic brain injury (TBI). Despite the high prevalence of PTE, current methods for predicting its occurrence remain limited. In this study, we aimed to identify imaging‐based markers for the prediction of PTE using machine learning. Specifically, we examined three imaging features: Lesion volumes, resting‐state fMRI‐based measures of functional connectivity, and amplitude of low‐frequency fluctuation (ALFF). We employed three machine‐learning methods, namely, kernel support vector machine (KSVM), random forest, and an artificial neural network (NN), to develop predictive models. Our results showed that the KSVM classifier, with all three feature types as input, achieved the best prediction accuracy of 0.78 AUC (area under the receiver operating characteristic (ROC) curve) using nested cross‐validation. Furthermore, we performed voxel‐wise and lobe‐wise group difference analyses to investigate the specific brain regions and features that the model found to be most helpful in distinguishing PTE from non‐PTE populations. Our statistical analysis uncovered significant differences in bilateral temporal lobes and cerebellum between PTE and non‐PTE groups. Overall, our findings demonstrate the complementary prognostic value of MR‐based markers in PTE prediction and provide new insights into the underlying structural and functional alterations associated with PTE.
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