Distinct Spectral and Directional Thalamocortical Network Dynamics Define Focal Seizure Evolution

Neuromodulation targeting thalamic nuclei is increasingly used to treat drug-resistant focal epilepsy, yet human intracranial EEG studies describing how thalamocortical interactions evolve across seizures remain limited. We aimed to define frequency-specific thalamocortical network dynamics from seizure onset to termination, compare thalamocortical and cortico-cortical network activation, and test whether thalamic EEG features can classify seizure state to inform closed-loop or adaptive thalamic stimulation strategies. We retrospectively analyzed chronic stereo-EEG recordings from 19 patients with pediatric-onset, drug-resistant focal epilepsy (6 females; age at thalamic recording 1.0-28.1 years, median 16.9) with cortical and thalamic sampling. Sixty-six focal seizures were included. Spectral power, imaginary coherence, and spectral Granger causality were computed in non-overlapping two-second windows across slow (1-12 Hz), beta (13-30 Hz), and gamma (30-70 Hz) bands and compared with an interictal baseline. Random forest classifiers were trained using thalamic spectral power and thalamocortical connectivity features to distinguish ictal from non-ictal states using leave-one-patient-out cross-validation, with Shapley additive explanations used for feature attribution. Visual analysis identified thalamic ictal involvement at seizure onset in 82/101 thalamic contacts (81.2%), increasing to near-universal involvement by seizure termination, with onset-to-termination patterns dominated by low-voltage fast activity at onset and rhythmic spike or rhythmic slow-wave patterns at termination. The thalamus and cortical seizure onset zone exhibited broadband power increases at seizure onset that attenuated toward termination, while slow- and beta-band thalamocortical connectivity increased throughout seizures and peaked around the end-of-seizure epoch. Directed connectivity demonstrated bidirectional thalamocortical coupling, with slow-frequency thalamus-to-seizure onset zone outflow exceeding propagation-zone-to-seizure onset zone cortico-cortical outflow during both ictal and end-of-seizure epochs (anterior nucleus: p = 9.06 × 10 ³ and p = 8.80 × 10 ³; centromedian nucleus: p = 3.30 × 10 ³ and p = 5.70 × 10 ³). Seizure state was classifiable from thalamic spectral power and thalamocortical network features, achieving an area under the receiver operating characteristic curve of 0.825 ± 0.163 (anterior nucleus model) and 0.839 ± 0.149 (centromedian nucleus model), with thalamic broadband power plus slow-frequency thalamus-to-cortex outflow and beta-frequency cortex-to-thalamus inflow among the most informative features. Leveraging human intracranial EEG data, we define coordinated, frequency- and direction-specific thalamocortical and cortico-cortical network dynamics that evolve from seizure onset to termination. These findings establish a mechanistic basis and identify actionable thalamocortical EEG targets-particularly slow- and beta-band interactions-to inform individualized, adaptive, closed-loop neuromodulation aimed at optimizing seizure outcomes.