# Impact of seizure onset pattern on temporal lobe seizure propagation through the basal ganglia

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $674,409

## Abstract

SUMMARY
The objective of this proposal is to investigate how temporal lobe (TL) seizures with different onset patterns
propagate through the basal ganglia (BG) and to evaluate the implication of this circuit in the control of TL
seizures. TL epilepsy is the most common form of focal epilepsy and a third of the patients do not respond to
drug therapy.
Resective surgery and deep brain stimulation can be effective, however, only some patients are
eligible and very few become seizure free.
There is then a clear need for better and more individualized epilepsy
treatments based on a rigorous understanding of the networks and brain structures implicated in TL seizures.
Studies on TL seizures have mainly focused on the interconnected structures of the limbic circuit, but there is
also strong evidence suggesting that the BG could be a key contributor to the propagation and control of TL
seizures. Several studies using neuropharmacological inhibition, electrophysiological recordings, metabolic
alterations, and advanced imaging have suggested an inhibitory role of the BG in TL epilepsy. However, findings
have been inconsistent, and the exact mechanisms and BG pathways implicated in TL seizures are still under
debate. These heterogeneous results may be explained by seizure onset patterns. Recent studies focusing on
the seizure pattern have proposed that the ictal activity originating from the same ictogenic area might propagate
through different pathways depending on the seizure pattern, which could potentially explain the heterogeneity
of previous findings. To better understand the implication of the BG and its dopaminergic system, we propose to
use a non-human primate model, as it captures characteristics of the BG specific to primates, including humans.
Our preliminary data support the hypothesis that seizures with a low amplitude, fast activity pattern will propagate
primarily through the putamen-substantia nigra (Put-SNr) pathway, while seizures with a high amplitude, slow
oscillation onset pattern are more likely to involve the nucleus accumbens-pallidum (NAcc-GPi) pathway. To
further investigate the role of these pathways, we propose to investigate how TL seizures with different onset
patterns propagate through the basal ganglia as well as the implication of these circuits in the control of TL
seizures. In Aim 1, we will record the unit and local field potential activity of the NAcc-GPi and the Put-SNr
pathway during TL seizures induced with intracerebral injection of penicillin. Based on the recordings performed
in Aim 1, we will identify the area of the NAcc and Put that is most affected by TL seizures. In Aim 2, we will
target these areas to evaluate the effect of dopaminergic modulation on TL seizures. Finally, in Aim 3, we will
simultaneously record the activity of the SNr and GPi during TL seizures, identify the area with the strongest
response, and evaluate the effect of pharmacological inhibition of the BG output structures on TL seizure
frequ...

## Key facts

- **NIH application ID:** 10859473
- **Project number:** 1R01NS136529-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Annaelle Devergnas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $674,409
- **Award type:** 1
- **Project period:** 2024-09-11 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859473

## Citation

> US National Institutes of Health, RePORTER application 10859473, Impact of seizure onset pattern on temporal lobe seizure propagation through the basal ganglia (1R01NS136529-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10859473. Licensed CC0.

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