Seizure network characterization by functional connectivity mapping and manipulation.

Significance: Despite the availability of various anti-seizure medications, nearly 1/3 of epilepsy patients experience drug-resistant seizures. These patients are left with invasive surgical options that do not guarantee seizure remission. The development of novel treatment options depends on elucidating the complex biology of seizures and brain networks.

Aim: We aimed to develop an experimental paradigm that uses anatomical network information, functional connectivity, and seizure models to determine how brain networks, and their manipulation, affect seizure propagation.

Approach: Guided by a known anatomical network, we applied widefield calcium imaging to determine how neural activity and seizures spread through the network regions, focusing on the primary somatosensory cortex and secondary motor cortex. We used microstimulation to induce suprathreshold excitatory activation and compared this reproducible stimulus with acute pharmacologically induced spontaneous seizure propagation. In a proof-of-concept experiment, we ablated a single node within this bilateral network and measured the effect on propagation and recruitment. Similar preliminary experiments were repeated in a chronic seizure model.

Results: The microstimulation of the somatosensory cortex propagated in a distinct pattern throughout the bilateral network with sequential reproducible node recruitment. Seizures recapitulated this same pattern, indicating a hijacking of existing pathways. Ablation of a key node in the network in the secondary motor cortex changed contralateral spread. Early chronic cobalt seizure data are presented.

Conclusion: Here, we demonstrate a paradigm for combining widefield calcium imaging with microstimulation, cortical ablation, and seizure mapping to determine how anatomical networks inform the propagation patterns of cortical seizures. These experiments can be extended to long-term tracking of epilepsy to study epileptogenesis in other cortical networks. Our proof-of-concept findings suggest that this paradigm may be useful in the development of novel therapies for drug-resistant epilepsy patients and can be extended to the study of other disorders involving brain networks.