Hidden behavioral fingerprints in epilepsy

Epilepsy is a major disorder affecting millions of people. Although modern electrophysiological and imaging approaches provide high-resolution access to the multi-scale brain circuit malfunctions in epilepsy, our un-derstanding of how behavior changes with epilepsy has remained rudimentary. As a result, screening for new therapies for children and adults with devastating epilepsies still relies on the inherently subjective, semi -quantitative assessment of a handful of pre-selected behavioral signs of epilepsy in animal models. Here, we use machine learning-assisted 3D video analysis to reveal hidden behavioral phenotypes in mice with ac-quired and genetic epilepsies and track their alterations during post-insult epileptogenesis and in response to anti-epileptic drugs. These results show the persistent reconfiguration of behavioral fingerprints in epi-lepsy and indicate that they can be employed for rapid, automated anti-epileptic drug testing at scale.