# Deficient inhibition underlies salience network hyperactivity in stress and anxiety

> **NIH NIH R21** · FLORIDA STATE UNIVERSITY · 2022 · $238,293

## Abstract

ABSTRACT
 Decades of research notwithstanding, there remains an urgent need to uncover the neurobiology
of stress and anxiety and develop effective biomarkers for these conditions. The salience network (SN),
a major intrinsic neural network anchored in the frontal lobe, consistently exhibits hyperactive functioning
in stress and anxiety. This SN hyperactivity has been recognized as a novel brain network pathology, but
its underlying mechanism remains elusive.
 EEG alpha (8-12 Hz) oscillations, dominating intrinsic neural rhythmic activity, play a critical role in
cortical inhibition. Particularly, prevalent posterior-to-frontal (P→F) alpha projection (i.e., alpha directional
connectivity) transmits alpha inhibitory influence from the occipitoparietal cortex (a primary alpha source)
to the frontal lobe. By driving bottom-up cortical inhibition and gating sensory propagation that triggers
the SN, alpha P→F connectivity can serve to downregulate the SN. Prominently featured in
“thalamocortical dysrhythmia” or “oscillopathy” models of neuropsychiatric disorders, alpha dysrhythmia
(particularly, deficient alpha P→F connectivity) has been increasingly observed in stress and anxiety,
motivating our hypothesis that deficient alpha P→F connectivity underlies SN hyperactivity in stress and
anxiety.
 Leveraging an integrative methodology of simultaneous EEG-fMRI combined with experimental
anxiety induction via stress exposure, this project (N = 140) will establish a mechanistic role of alpha
P→F hypoconnectivity in the genesis and maintenance of SN hyperactivity in stress and anxiety. This
discovery will further identify an accessible, low-cost EEG biomarker for SN hyperactivity and for stress
and anxiety in general. Finally, this discovery will isolate a new treatment target that is highly responsive
to non-invasive brain stimulation (NIBS), motivating an R01 to normalize alpha P→F connectivity as a
novel intervention for stress and anxiety.

## Key facts

- **NIH application ID:** 10377665
- **Project number:** 1R21MH126479-01A1
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Wen Li
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,293
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377665

## Citation

> US National Institutes of Health, RePORTER application 10377665, Deficient inhibition underlies salience network hyperactivity in stress and anxiety (1R21MH126479-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10377665. Licensed CC0.

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