Drug-resistant epilepsy affects tens of millions of people worldwide and is associated with considerable morbidity and mortality. Thalamic deep brain stimulation and cortical responsive neurostimulation are proven treatments for focal epilepsy. Both have been used to target a range of thalamic nuclei, yet the roles of these thalamic nuclei in focal seizure generation remain incompletely understood. Thirteen patients with drug-resistant focal epilepsy undergoing intracranial EEG were consented to undergo investigation of thalamocortical networks. Sampled regions included cortical, mesial temporal, and thalamic brain regions. Visual and spectral analyses were performed to identify seizure onset patterns and correlate thalamic and cortical seizure activity. Thalamic ictal discharges were observed in all patients, including synchronous thalamocortical seizure onset discharges with distinct onset patterns. These onset patterns ranged from hypersynchronous spiking, low-voltage fast activity, ictal baseline shifts, to broadband suppression. Multiple thalamic nuclei were involved in ictal organization and propagation, with the specific nuclei depending on the cortical seizure network. The thalamus plays a crucial role in focal onset seizure generation and propagation, with distinct seizure onset patterns and nuclei involved. These findings support exploring a broader range of thalamic nuclei in epilepsy neurostimulation and have implications for seizure detection settings in intracranial sensing devices.

Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague Prague Czech Republic

Department of Neurology Alfred Health 55 Commercial Rd Melbourne VIC 3004 Australia

Department of Neurology Mayo Clinic 200 1 St SW Rochester MN 55905 USA

Department of Neuroscience Monash University 99 Commercial Rd Melbourne VIC 3004 Australia

Department of Neurosurgery Mayo Clinic 200 1 St SW Rochester MN 55905 USA

Faculty of Biomedical Engineering Czech Technical University Prague Kladno Czech Republic

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