# Non-Invasive Methods to Drive Neural Activity with Millisecond Precision and to Recruit the Brain’s Immune Cells

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $110,753

## Abstract

The parent grant has shown that non-invasive flickering sensory stimulation entrains multiple specific frequencies
of neural activity and gamma frequency sensory stimulation recruits immune signals and cells microglia to engulf
pathogenic proteins in mouse models for AD. In addition, the parent grant is actively investigating the effects of
sensory stimulation on neural codes and synapses. The goal of this proposal is to determine which, if any,
patterns of sensory flicker restore healthy synaptic and microglia functions following chronic stress. Individuals
that have suffered from chronic or severe stress have a 2-fold or greater increased risk of developing AD. Loss
of synaptic integrity is one of the best predictors of neuropsychiatric and cognitive decline in AD. Stress increases
the risk of AD and associated neuropsychiatric symptoms by promoting synapses loss in corticolimbic brain
regions due to enhanced synaptic pruning by dysfunctional microglia, the primary immune cells of the brain.
Furthermore, mounting evidence suggests that chronic stress accelerates the progression of AD-associated
pathology including the accumulation of aggregated amyloid-β (Aβ) peptide and amyloid plaques. Accordingly,
we will determine if chronic sensory flicker exposure prevents stress-induced synaptic loss, accelerated amyloid
accumulation, and microglia-mediated synapse remodeling in corticolimbic brain regions following chronic stress
in WT and 5XFAD mice. This research will be the first to identify how stress-induced synaptic loss, accelerated
pathology accumulation, and immune dysfunction is halted by flicker stimulation. Identifying the effects of flicker
on stress-induced pathology will reveal a role for specific frequencies of neural activity on stress neurobiology
and provide the foundation for using this non-invasive stimulation as a novel therapeutic approach to prevent
stress-induced decline in AD. Because individuals are twice as likely to develop AD following chronic or severe
stress, prevention of the neurobiological effects of stress would severely reduce the prevalence of AD.

## Key facts

- **NIH application ID:** 10301791
- **Project number:** 3R01NS109226-04S2
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Annabelle Catherine Singer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $110,753
- **Award type:** 3
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301791

## Citation

> US National Institutes of Health, RePORTER application 10301791, Non-Invasive Methods to Drive Neural Activity with Millisecond Precision and to Recruit the Brain’s Immune Cells (3R01NS109226-04S2). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10301791. Licensed CC0.

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