HIPPOCAMPAL TAU RELATED SIGNAL INDEXES HYPEREXCITABILITY AND NREM SLEEP MEMORY DYSFUNCTION IN TEMPORAL LOBE EPILEPSY

Arafat, T.; Schiller, K.; Lam, J.; Von Ellenrieder, N.; Cai, Z.; DeKraker, J.; Fadaie, F.; Sziklas, V.; Crane, J.; Cruces, R. R.; Hopewell, R.; Hsiao, C.; Massarweh, G.; Soucy, J.-P.; Erlandsson, K.; Hosseini, S. A.; Chan, T.; Kobayashi, E.; Rosa-Neto, P.; Bernasconi, A.; Bernasconi, N.; Koepp, M.; Gotman, J.; Bernhardt, B.

doi:10.64898/2026.09.07.748279

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bioRxiv · 10.64898/2026.09.07.748279

HIPPOCAMPAL TAU RELATED SIGNAL INDEXES HYPEREXCITABILITY AND NREM SLEEP MEMORY DYSFUNCTION IN TEMPORAL LOBE EPILEPSY

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Abstract

Background Sleep and memory disturbances are common in temporal lobe epilepsy (TLE), yet their relationship with tau-targeted neuroimaging measures remains unclear. We investigated whether in-vivo temporal 18F-MK6240 tracer retention relates to seizure burden, non-rapid eye movement (NREM) sleep microstructure, and memory performance in TLE. Methods This cross-sectional study was conducted from 2019 to 2024 at the Montreal Neurological Institute-Hospital. Eligible patients had unilateral TLE diagnosed according to International League Against Epilepsy criteria and underwent overnight electroencephalography (EEG) recordings, research-protocol 3T magnetic resonance imaging, and 18F-MK6240 positron emission tomography. Regional 18F-MK6240 standardized uptake value ratios (SUVRs), using the cerebellum as the reference region, were quantified in the ipsilateral hippocampus (defined a priori as the primary region of interest), as well as in peri-hippocampal and lateral temporal regions. Electroclinical and neuropsychological measures, including seizure burden (high vs low), N2 interictal epileptiform discharge frequency (frequent vs non-frequent), and memory performance (impaired vs intact), were classified according to predefined clinical criteria. N2 spindle rate and N3 slow-wave rate were quantified from overnight EEG recordings. Findings Of 70 eligible patients, 25 were included (eight [32%] females; mean age 35.2 years [SD 12.1]). Higher ipsilateral hippocampal 18F-MK6240 uptake was observed in participants with greater focal seizure burden (median [IQR] 0.70 [0.67-0.78] vs 0.64 [0.58-0.65], rank-biserial correlation=-0.58, 95% CI -0.82 to -0.19; p=0.02), was associated with lower N2 spindle rate (r=-0.42, 95% CI -0.70 to -0.03; p=0.04) and higher N3 slow-wave rate (r=0.47; 95% CI 0.09 to 0.73; p=0.02), and was also higher in participants with impaired than intact memory performance (n=21; mean [SD] 0.80 [0.12] vs 0.68 [0.10], Cohen's d=1.15, 95% CI 0.07 to 2.21; p=0.04). Associations outside the hippocampus were generally less consistent and less precise, with the largest non-hippocampal estimate observed in peri-hippocampal regions. Interpretation Higher hippocampal 18F-MK6240 uptake was associated with greater focal seizure burden, altered NREM sleep microstructure, and impaired memory performance in TLE. These findings suggest that hippocampal 18F-MK6240 uptake may represent a candidate marker of circuit vulnerability associated with NREM sleep-memory dysfunction in TLE, warranting validation in larger longitudinal studies.

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Arafat, T., Schiller, K., Lam, J., Von Ellenrieder, N., Cai, Z., DeKraker, J., Fadaie, F., Sziklas, V., Crane, J., Cruces, R. R., Hopewell, R., Hsiao, C., Massarweh, G., Soucy, J.-P., Erlandsson, K., Hosseini, S. A., Chan, T., Kobayashi, E., Rosa-Neto, P., Bernasconi, A., Bernasconi, N., Koepp, M., Gotman, J., Bernhardt, B.. 2026-09-13. HIPPOCAMPAL TAU RELATED SIGNAL INDEXES HYPEREXCITABILITY AND NREM SLEEP MEMORY DYSFUNCTION IN TEMPORAL LOBE EPILEPSY. https://doi.org/10.64898/2026.09.07.748279

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