The thalamus plays an important role in key clinical conditions of focal temporal lobe epilepsy (TLE), but no investigation has examined whether the same thalamic local and connectome properties shape a patient’s status across these different conditions. This retrospective longitudinal MRI study used resting-state fMRI and structural imaging to identify whole-brain focal/regional and connectome-level features associated with six binary clinical conditions of TLE (pre/post-surgery, seizure and neurocognitive outcomes, pathology, seizure subtype, and SOZ lateralization) in 91 patients across two centers (age range: 15–65 years) and 85 matched healthy participants (age range: 18-60 years). Across conditions, relative to all other brain regions, thalamic features exert the strongest influence. Specifically, thalamic focal and connectome intrinsic activity and gray matter volume are robustly associated with post-surgical reorganization. Pre-surgical thalamic hyperconnectivity predicts poorer seizure control, whereas post-surgical reorganization is not associated with either seizure outcome. Neuropsychological outcomes are subsequently examined and show associations with local ipsilateral thalamic properties. Namely, pre-surgical organization of the ipsilateral thalamus is associated with better preservation of cognitive performance, whereas post-surgical organization is associated with greater cognitive decline. Our results expand and refine our understanding of the thalamus as a region showing robust and recurrent associations across multiple clinical conditions of TLE. Importantly, we distinguish its role in pre- versus post-surgical brain organization with respect to seizure and neuropsychological outcomes, highlighting its importance for planning and prognosis in epilepsy surgery. This study examined how the thalamus, a deep brain structure important for communication between brain regions, relates to several major clinical features of temporal lobe epilepsy. Using MRI scans collected before and after surgery, we analyzed both local brain activity and broader network connections to understand how different brain characteristics shape seizure control and cognitive changes. We found that the thalamus plays a central role across many clinical conditions, influencing both surgical outcomes and cognition after surgery. Importantly, thalamic features measured before surgery helped predict which patients would continue to have seizures, while changes after surgery were linked to declines in memory and language. These findings may improve pre-surgical evaluations and help guide individualized treatment planning for patients with epilepsy. Zhang et al. examine local and connectome brain features across six clinical conditions in temporal lobe epilepsy using a whole-brain analytic framework. They find that thalamic organization shows the strongest cross-condition influence and that pre- versus post-surgical thalamic profiles relate differently to seizure and cognitive outcomes.
Zhang et al. (2026) studied this question.