Thalamo-cortical Synchrony Shapes Seizure Expression in Human Temporal Lobe Epilepsy

Abstract In drug-resistant temporal lobe epilepsy (DR-TLE), electrographic seizures with clinical symptoms (CS) largely determine quality of life, yet some remain silent (NCS) despite arising from the same seizure-onset zone (SOZ). While surgical resection can be curative in select cases, many patients particularly those with bilateral TLE or unresectable networks are not surgical candidates. For these individuals, clarifying why some seizures produce symptoms while others do not is essential for advancing therapy. We hypothesized that thalamo-cortical network engagement may explain this divergence. 286 seizures from 62 DR-TLE patients, included coverage of the pulvinar and/or anterior thalamic group, were analyzed. Thalamo-cortical synchrony, quantified as the correlation between time–frequency patterns in thalamic nuclei and the cortical SOZ, was investigated in relation to seizure type, epilepsy subtype, thalamic region, and one-year post-resection surgical outcome. Thalamo-cortical synchrony was stronger during CS than NCS (p < 0.0001, δ > 0.6), regardless of epilepsy subtype, thalamic region, seizure subtype, or outcome, and confirmed within patients. Multivariate analysis identified seizure type as the only independent predictor (p < 0.001). These findings establish thalamo-cortical synchrony as a network-level marker of clinical seizure expression and highlight the potential of neuromodulation to modulate seizure expression when resection is not feasible.