Noninvasive Seizure Screening in Preclinical Models of Epilepsy

Noninvasive Seizure Screening in Preclinical Models of Epilepsy
There is an urgent need for research into treatment options for epilepsy and other seizure disordersAnimal
models are increasingly used to understand disease mechanisms and to screen promising therapeutic
approachesAnimal epilepsy model use typically requires expensive and labor intensive experimentationwith
invasive EEG measurements being the preferred method of validationThis severely limits the pace and scale of
investigationIn models of acquired epilepsyanimals usually undergo treatment to induce status epilepticusa period of unremitting seizure followed by a latent period during which the brain rewires itself to generate
spontaneously recurring seizuresevidence of chronic epilepsyThe duration of the latent period and the
likelihood that an animal will develop epilepsy are both uncertainAnimals must be observed for weeks to
confirm epilepsy before they are ready for experimentationDuring this latent periodseizures are commonly
documented by visual observation or video reviewwhich are tedious and prone to errorA commercial system
for automated noninvasive seizure detection would therefore be attractive to epilepsy researchersSignal SolutionsLLChas developed technology based on piezoelectric sensors for noninvasivehighthroughput behavioral monitoring of rodents that is currently used by research groups around the world to
identify genes related to sleep and circadian rhythmsThe system discriminates sleep from wakefulness with
overaccuracyThe Sunderam Lab at the University of Kentucky has further demonstrated using EEG
analysis that these piezo sensors can be used to label REM and NREM stages of sleep in miceIn this STTR proposalPI Sunderam and co investigator Bauer will work with Signal Solutions to develop
methods based on the piezo technology for accurate noninvasive seizure screening in rodent models of
epilepsyThe result will be a validated system that minimizes the need for invasive and resource intensive EEG
analysis or tedious video monitoringThe objectives of the project are the followingTest the feasibility of
coarse detection of epilepsy onset in rodents using a noninvasive piezo sensorTrain a piezo classifier to
accurately detect and quantify seizures in rodents with confirmed epilepsyandTest the utility of a miniature
piezo sensor for seizure screening and an infrared imager for seizure verification and severity assessmentThe envisioned product is a turnkey system for convenient and noninvasive seizure screening in small animal
models of epilepsy in custom or commercial cagesPotential customers include academic research labs as well
as labs in the pharmaceutical sector engaged in high volume screening of antiepileptic drugs The development of treatments for epilepsy depends heavily on laboratory animal studies in which the effect of
treatment on seizures is measuredSeizures are rare and unpredictableand monitoring animals for seizures
requires tedious observation or review of video recordingsthe alternative is to record brain signalswhich
requires invasive surgery to implant electrodesA new technology is proposed here that would enable
completely noninvasive detection of seizures in animalsThe accuracy of this method will be compared with
EEG analysis in an animal model of epilepsy