# Asynchronous distributed multielectrode neuromodulation for epilepsy

> **NIH NIH UG3** · EMORY UNIVERSITY · 2020 · $450,559

## Abstract

PROJECT SUMMARY
Epilepsy, occurring in 1 percent of the world’s population, is associated with disability, injury,
cognitive and neurological dysfunction, depression, loss of productivity, socioeconomic decline
and even death. Of this population, 30 percent of epilepsy cases are medically intractable, leaving
surgical interventions as the only option for treatment. Whereas open resection, the current
surgical standard of treatment, can yield seizure freedom rates as high as 60-80 percent, these
are often associated with cognitive dysfunction and focal neurological deficits. Particularly,
patients with dominant hemisphere mesial temporal lobe epilepsy (MTLE), the target population
for this proposal, are at risk for significant decline in memory and associated disability. The only
option for these patients at present is electrical neuromodulation which, although effective at
reducing seizures, only achieves seizure freedom in ~10% of patients. We have recently found
that delivering asynchronous pulses distributed across a multielectrode array of 16
microelectrodes, and stimulated at low (theta) frequency, is more effective than macrostimulation
in controlling seizures in a rodent model of MTLE. The objective of the proposed project is to
optimize asynchronous distributed multielectrode stimulation (ADMES) in a realistic large animal
model of epilepsy - non-human primates (NHP) that have been administered penicillin (PCN) in
the hippocampus to induced repeated spontaneous seizures. This research will capitalize on the
availability of a new commercial neurostimulation system (RC+S, Medtronic) that uniquely allows
our novel approach to be implemented. We will also exploit the novel bi-directional feature of this
unit to optimize our therapy with both open-loop and closed-loop approaches to ADMES. We will
first implement ADMES in our NHP model and quantify effects on seizure frequency and length,
and rule out adverse effects on recognition memory. In parallel, we will characterize the response
of physiological biomarkers such as synchrony to adjustment of ADMES stimulation in an
externalized system. This will allow us to develop both open-loop and closed-loop control policies
to optimize these biomarkers as a proxy for seizure control. The most effective stimulation
parameters will be implemented in 8 NHPs using the RC+S neurostimulator and benefit on seizure
frequency and effects on memory will be evaluated. If seizure reduction is ≥50% then we will
advance to an early clinical feasibility study. For this, we will first identify electrophysiological
biomarkers and characterize the effects of stimulation parameters informed from our NHP study
on those biomarkers during invasive monitoring of MTLE patients and then move to an early
feasibility trial of ADMES in 6 patients. The final stimulation parameters will be implemented in
RC+S and behavioral seizure reduction and memory testing for safety will be quantified over 12
months. At the completion of thi...

## Key facts

- **NIH application ID:** 9749270
- **Project number:** 5UG3NS100559-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Annaelle Devergnas
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,559
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9749270

## Citation

> US National Institutes of Health, RePORTER application 9749270, Asynchronous distributed multielectrode neuromodulation for epilepsy (5UG3NS100559-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9749270. Licensed CC0.

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