Abstracts

Rationale: Closed-loop neuromodulation is being actively investigated as a treatment for a number of neurological conditions. The NeuroPace® RNS® System for epilepsy is the first closed-loop responsive neurostimulation system approved by the FDA for the treatment of intractable partial onset seizures in adults. The technological capabilities of the RNS® System and of custom-designed accessories for external computer control may lend themselves to research applications.Methods: The RNS® System includes a cranially implanted neurostimulator connected to 1‑2 quadripolar depth or cortical strip leads. Electrocorticographic (ECoG) signals are continuously monitored through four differential amplifiers with a 250 Hz sampling rate and four separately configurable amplitude- and frequency-based pattern detectors. The neurostimulator is programmed by the physician to detect specific electrographic patterns (biomarkers) that may be associated with neurological states or symptoms. Up to 30 channel-minutes of scheduled or event-triggered ECoG recordings can be stored in the neurostimulator along with time-stamped event records and 28 days of hourly detection and therapy counts. These data can be wirelessly downloaded from the neurostimulator by the patient and uploaded to the NeuroPace® Patient Data Management System for physician review. Electrical stimulation can be administered in response to biomarker detection or commanded manually using a physician programmer and wireless telemetry. Current-controlled symmetric biphasic square wave pulses (0-12 mA, 1-333 Hz, 40-1000 µs pulse width) are configured by the physician and delivered in 1-2 bursts for up to 5 sec (responsive) or 30 sec (manual). In the clinic, investigational studies can be performed using an external computer and research accessories designed by NeuroPace to acquire over an hour of continuous ECoG data, to insert ECoG markers, and to deliver stimulation. ECoG data may be transferred to IEEG.org for cloud-based analysis and direct access from MATLAB.Results: Given its capabilities, a potential research use of the RNS® System might be in a memory encoding and recall investigation. NeuroPace successfully simulated a possible experimental protocol that included visual stimulus presentation, open- and closed-loop theta-frequency stimulation during encoding and recall, concurrent sensing and stimulation, acquisition of real-time and stored ECoGs, and ECoG markers for alignment of experimental data with ECoG recordings.Conclusions: The NeuroPace® RNS® System is well suited for clinical research because of its flexible detection and closed-loop stimulation capabilities. In the clinic, ECoGs can be recorded continuously for up to an hour and then synchronized with behavioral data. An investigational external computer can control the RNS® System through research accessories customized for the experiment. During these investigations, open-loop computer-controlled stimulation and/or closed-loop responsive stimulation can be used to modulate neural activity. Thus, the RNS® System may be used to explore mechanisms of cognitive brain function and neurological disease. (Supported by DARPA RAM)