Atypical intrinsic neural timescales in temporal lobe epilepsy

Objective: Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting-state functional magnetic resonance imaging (rs-fMRI), we mapped the whole-brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE-related structural compromise. Finally, we evaluated the clinical utility of INT.Methods: We studied 46 patients with TLE 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 the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left- vs right-sided seizure onset.Results: Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT-derived classifiers discriminated 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 accuracy and cross-site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds.Significance: Our findings 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 emphasizes promising clinical utility.11Nsciescopu

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment