# Ventral pallidum deep brain stimulation for epilepsy

> **NIH NIH R56** · ALBANY MEDICAL COLLEGE · 2020 · $448,292

## Abstract

PROJECT SUMMARY
 Antiepileptic drugs are the primary treatment option for individuals with epilepsy. However, many are
refractory to this approach and require other therapeutics such as resective surgery. Unfortunately, few
undergo this procedure due to low candidacy or referral rates and ~35% still have seizures even after surgery.
Therefore, there’s an urgent unmet need to provide seizure freedom for refractory individuals using alternative
approaches. Neuromodulation, and in particular deep brain stimulation (DBS), may accomplish this goal, but
current options such as vagus nerve stimulation (VNS), responsive neurostimulation (RNS) and anterior
thalamus deep brain stimulation (ANT-DBS) provide limited seizure-freedom. Therefore, current
neuromodulatory options fall short of potently treating refractory epilepsy.
 Recently, our data revealed that DBS of the ventral pallidum (VP), a basal ganglia structure, prevented
partial and secondarily generalized forebrain seizures and brainstem seizures in the pilocarpine rat model of
temporal lobe epilepsy (TLE). Conversely, VNS, RNS and ANT-DBS reduce or delay seizures in comparable
preclinical studies. While compelling, our findings are from animals with acute seizures and not spontaneous
recurrent seizures (SRSs). Therefore, it remains to be determined whether VP-DBS possess similar efficacy in
rats with seizures that more closely resemble human epilepsy. In light of this and keeping in mind VP-DBS
potent efficacy in preventing brainstem seizures, we formulate an overarching hypothesis that ventral pallidum
deep brain stimulation prevents spontaneous recurrent seizures and mitigate cardio-respiratory dysfunction by
inhibiting electrographic seizures in specific epileptic foci and preserving functional fidelity in autonomic
brainstem areas, respectively. To test this, we employ video-electroencephalogram (EEG) monitoring, in vivo
and in vitro electrophysiology, electrocardiogram (ECG)-telemetry and whole-body plethysmography
technology and immunocycto-histochemistry to accomplish the following specific aims: 1) determine if VP-DBS
prevents spontaneous recurrent seizures; 2) identify specific epileptic foci inhibited by VP-DBS responsible for
preventing spontaneous recurrent seizures; and lastly, 3) determine if VP-DBS mitigate cardio-respiratory
dysfunction by preserving functional fidelity of neurons in brainstem autonomic centers controlling their activity;
specifically in the nucleus of solitary tract (NTS) and pre-botzinger complex (PBC).
 Altogether, findings from our study will underscore VP-DBS as a potent neuromodulatory approach for
controlling seizures in epilepsy and reveal potential underlying neural substrates contributing to this efficacy.
Lastly, it will show that VP-DBS has provocative utility in mitigating cardio-respiratory dysfunction during
generalized seizures by preserving functional fidelity of brainstem areas that control these functions.

## Key facts

- **NIH application ID:** 10129451
- **Project number:** 1R56NS101224-01A1
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Damian Seung-Ho Shin
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,292
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129451

## Citation

> US National Institutes of Health, RePORTER application 10129451, Ventral pallidum deep brain stimulation for epilepsy (1R56NS101224-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129451. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*