Early and widespread engagement of the cerebellum during hippocampal epileptiform activity Format: Brief Communication.

Despite research illustrating the cerebellum may be a critical circuit element in the epilepsies, remarkably little is known about cerebellar engagement during seizures. We therefore implemented a novel method for repeated imaging of the cerebellum in awake, chronically epileptic animals. We found widespread changes in cerebellar calcium signals during behavioral seizures and during hippocampal seizures that remained electrographic only, arguing against cerebellar modulation simply reflecting motor components. Moreover, even brief interictal spikes produced widespread alterations in cerebellar activity. Changes were noted in the anterior and posterior cerebellum, along the midline, and both ipsilaterally and contralaterally to the seizure focus. Remarkably, changes in the cerebellum also occurred prior to any noticeable change in the hippocampal electrographic recordings, suggesting a special relationship between the cerebellum and hippocampal epileptiform activity. Together these results underscore the importance of the cerebellum in epilepsy, warranting a more consistent consideration of the cerebellum when evaluating epilepsy patients.

The bidirectional relationship between the cerebellum and seizure networks: a double-edged sword.

Epilepsy is highly prevalent and notoriously pharmacoresistant. New therapeutic interventions are urgently needed, both for preventing the seizures themselves as well as negative outcomes and comorbidities associated with chronic epilepsy. While the cerebellum is not traditionally associated with epilepsy or seizures, research over the past decade has outlined the cerebellum as a brain region that is uniquely suited for both therapeutic needs. This review discusses our current understanding of the cerebellum as a key node within seizure networks, capable of both attenuating seizures in several animal models, and conversely, prone to altered structure and function in chronic epilepsy. Critical next steps are to advance therapeutic modulation of the cerebellum more towards translation, and to provide a more comprehensive characterization of how the cerebellum is impacted by chronic epilepsy, in order to subvert negative outcomes.