Atypical intrinsic neural timescales in temporal lobe epilepsy

Abstract Objective Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Here, we aimed to profile local neural function in TLE in vivo , building on prior evidence that has identified widespread structural alterations. Using multimodal MRI, we mapped intrinsic neural timescales (INT) at rest, examined associations to TLE-related structural compromise, and evaluated the clinical utility of INT. Methods We studied 46 TLE patients and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored effects of age and epilepsy duration. A supervised machine learning paradigm assessed utility of INT for classifying patients- vs -controls and seizure focus lateralization. Results Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in ipsilateral medial and lateral temporal regions, and sensorimotor cortices. Findings were consistent in each site and robust, albeit with reduced effect sizes, when correcting for structural alterations. TLE-related INT reductions increased with advancing disease duration, yet findings differed from aging effects seen in controls. Classifiers based on INT distinguished patients- vs -controls (balanced accuracy, 5-fold: 76±2.65%; cross-site, 72-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96±2.10%; cross-site, 95-97%) with high accuracies and generalization. Conclusions Our findings robustly demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which suggests clinical utility.