Abstracts

Rationale: Studies investigating responsive neurostimulation therapy for epilepsy in rat models have been labor intensive and thus limited by low sample sizes and short experiment durations. Additionally, findings from acute studies may not translate to clinical chronic conditions. To overcome the limitations of acute studies, a rat epilepsy monitoring system must be capable of long-term electrographic and behavioral data acquisition, and delivering customized stimulation patterns in a closed-loop fashion. No suitable commercial systems are available. We developed a 24 hour, 7 days a week continuous video/EEG system capable of closed-loop stimulus delivery and scalable for higher subject counts.Methods: Rats implanted with two bipolar stimulating/recording electrodes and screw EEG electrodes were affixed with a custom two-piece headmount (Fig 1-1) consisting of a disposable cranial frame and a reusable printed circuit board (PCB). Electrodes were soldered to the PCB to provide external electrical connections via an onboard connector. EEG signals were acquired via a stimulation-capable cable pre-amplifier (Fig 1-2). Amplified EEG signals were transmitted via an electrical swivel (Fig 1-3) to an EEG Data Acquisition System (DAS, Fig 1-4), recording three channels of continuous differential EEG. The real time EEG signals were passed from the DAS to an interface box (Fig 1-5) where the signals were sent to the NeuroPace, Inc. RNS System neurostimulator (NS). The NS was programmed to detect specified patterns of epileptiform activity on two of the EEG channels. Upon detection, the NS sent a digital trigger to an isolated stimulus generator (Fig 1-6). The stimulus generator then delivered customized analog electrical stimulation and a digital control signal via the electrical swivel (Fig 1-3) through the pre-amp (Fig 1-2), thus delivering the stimulation current to the animal via the recording electrode. The system also includes a unique clear acrylic cage (Fig 1-7) designed to house the animal and provide backlighting for continuous video recording with a CCD video camera (Fig 1-8). The video was processed in real-time using Seizure Scan software from Clever Sys, Inc. (Fig 1-9) to detect behavioral seizures. Stored video was later edited to create video clips corresponding to behavioral seizures and electrographic events as detected by post-hoc analysis.Results: This system has been successfully implemented in an ongoing study of the Tetanus Toxin and Pilocarpine models of chronic epilepsy in rodents. Continuous video/EEG data for periods of up to 30 days have been collected in over 100 animals with delivery of closed-loop stimulation therapy.Conclusions: This research system overcomes many limitations of acute studies in rodent models of epilepsy by allowing continuous EEG and video behavioral monitoring of treated animals with the ability to deliver closed loop stimulation in real time in response to detected electrographic activity, allowing for a greater degree of clinical relevance than previously possible. (Supported by NINDS 1U01NS064049-01A1)