# Deciphering the genomic mechanisms underlying the physiology of human brain stimulation

> **NIH NIH RF1** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $211,227

## Abstract

PROJECT SUMMARY
The underlying mechanisms of brain stimulation in humans are poorly understood, especially at the level of gene
expression. To address this gap in knowledge, in the parent award, we proposed a series of three experiments
that take advantage of the opportunity to obtain high-quality human neural tissue from neurosurgical patients in
order to measure the impact of brain stimulation on gene expression. Our experiments will generate data from
human subjects that underwent neurostimulation and unstimulated control subjects to measure the impact of
stimulation on brain circuit changes and their underlying gene expression signature. Our study team has seven
years of experience analyzing gene expression using an established pipeline for studying human cortical tissue
from neurosurgical patients, including application of cutting-edge methods for measuring gene expression.
These methods include single nuclei RNA-sequencing (snRNA-seq) and the exciting addition of single nuclei
ATAC-sequencing (snATAC-seq) to understand stimulation-related changes in transcription factors and
chromatin remodeling. Our hypotheses regarding specific gene classes were developed from our published data
correlating gene expression changes with neurophysiological signatures (brain oscillations) linked with
successful memory formation. In this administrative supplement, we will integrate the multiomic datasets being
generated in the parent award with available human brain genomic datasets from BRAIN Initiative mechanisms.
We will determine how our stimulation paradigms both in vivo and in organotypic slice culture (OSC) mimic
genomic features of other human brain datasets both over development and/or with underlying disease
pathology. We will test if stimulation reverses gene expression programs relevant to disease. In Aim 1, we will
integrate our datasets with those derived across development. In Aim 2, we will integrate our datasets with those
derived from individuals with a number of brain disorders, and we will use the integrated data from Aim 1 as
comparison. In Aim 3, we will directly examine whether stimulation mimics control or disease genomic states
more closely. The experience of our research team and proven record in publishing data using neurosurgical
tissue specimens, especially within the context of genomic analyses, supports our expectations of success.

## Key facts

- **NIH application ID:** 10834634
- **Project number:** 3RF1NS126143-01A1S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Genevieve Konopka
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $211,227
- **Award type:** 3
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834634

## Citation

> US National Institutes of Health, RePORTER application 10834634, Deciphering the genomic mechanisms underlying the physiology of human brain stimulation (3RF1NS126143-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834634. Licensed CC0.

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