# Deconstructing antiseizure mechanisms of anterior thalamic nucleus electrical stimulation

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $546,626

## Abstract

PROJECT SUMMARY/ABSTRACT
Epilepsy is one of the most prevalent neurological disorders. Patients with epilepsy experience abnormal brain
activity causing seizures or periods of unusual behavior, sensations, and often loss of awareness or
consciousness. Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an approved
therapy that effectively reduces seizures in many patients with drug resistant epilepsy, but very rarely leads to
all-important complete freedom from disabling seizures. This gap in treatment effectiveness may stem from
limited understanding of the mechanism underlying ANT-DBS, as it remains unknown not only which areas of a
complex neuronal network ANT-DBS must modulate, but also how those structures are modulated, to achieve
its therapeutic effect. We hypothesize that ANT-DBS results in direct, local inhibition of ANT neurons, and its
downstream pathway. We propose a set of experiments to identify and modulate the neuronal network
components that mediate ANT-DBS effectiveness, using the intrahippocampal kainic acid mouse model of
temporal lobe epilepsy. We will first determine whether ANT neurons contribute to the seizure suppressive effect
of ANT-DBS by ablating or modulating subpopulations of intrinsic neurons (Aim1). We then will examine whether
the ANT-retrosplenial cortex (RSCx) pathway is a necessary conduit for ANT- DBS to be effective, by
manipulating RSCx neurons that receive direct input from the ANT (Aim 2). Finally, we will test the hypothesis
that ANT-DBS might suppress seizure by inhibiting afferent axons from areas projecting to the ANT, such as the
mammillary bodies (Aim 3). Identifying the circuit mechanism of ANT-DBS would improve patient outcomes by
leading to more precise guidelines for improved device targeting, prediction of patients that respond to ANT-
DBS, and pave the way for novel therapies that can target this seizure-resistant network or use similar
mechanisms.

## Key facts

- **NIH application ID:** 10812858
- **Project number:** 1R01NS129984-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** ROBERT E GROSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $546,626
- **Award type:** 1
- **Project period:** 2024-08-20 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812858

## Citation

> US National Institutes of Health, RePORTER application 10812858, Deconstructing antiseizure mechanisms of anterior thalamic nucleus electrical stimulation (1R01NS129984-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10812858. Licensed CC0.

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