# Intraoperative 40 Hz Visual Light Flicker Attenuates Anesthesia/Surgery‐Induced Cognitive Impairments in Elderly Mice With Enhanced Cortical‐Hippocampal Coherence

**Authors:** Jingyao Jiang, Xin Huang, Jin Liu, Juan Xin, Lanyu Zhang, Zhicheng Yue, Qian Li, Tao Zhu, Peng Liang, Zhiyu Huang, Bhushan Sandeep, Jing Yang, Cheng Zhou

PMC · DOI: 10.1002/cns.70809 · CNS Neuroscience & Therapeutics · 2026-03-07

## TL;DR

Exposing elderly mice to 40 Hz light flicker during surgery helps prevent cognitive decline by improving brain connectivity between the visual cortex and hippocampus.

## Contribution

The study reveals that 40 Hz visual stimulation preserves cognitive function in elderly mice by enhancing cortical-hippocampal gamma coherence during surgery.

## Key findings

- 40 Hz flicker improved cognitive function impaired by anesthesia or surgery.
- 40 Hz stimulation enhanced gamma coherence between the visual cortex and hippocampus.
- Gamma frequency power increased in the hippocampus following 40 Hz stimulation.

## Abstract

Forty Hz light flicker has shown promise in mitigating cognitive impairments, though its mechanisms remain unclear.

This study aimed to use perioperative neurocognitive dysfunction (PND) as a unique model of neural damage to provide a broader understanding of the neural mechanisms underlying the cognitive improvements associated with 40 Hz visual stimulation and offer new insights into the clinical application of PND treatment.

Postoperative cognitive function was assessed through behavioral tests. Male and female mice received various visual light flicker stimuli, including 40 Hz, random, continuous, or no light. Local field potentials were recorded from the hippocampal dentate gyrus (DG) and primary visual cortex.

Our results show that among the stimuli, only the 40 Hz flicker improved cognitive function, impaired by anesthesia or surgery. Intraoperative 40 Hz stimulation activated the primary visual cortex and was correlated with enhanced gamma coherence between this region and the hippocampal DG, a coherence that surgery itself notably reduced. This preserved functional connectivity. Additionally, hippocampal DG activity was enhanced, particularly in the gamma frequency range.

Our results suggest that 40 Hz flicker mitigates anesthesia/surgery‐induced cognitive deficits, potentially through modulating gamma coherence between the visual cortex and hippocampus. These findings provide insights into PND prevention and the neural mechanisms underlying 40 Hz‐induced cognitive benefits.

Light flicker activated the visual cortex intraoperatively, including: a reduction in electrical activity suppression, and enhancement of high‐frequency gamma wave power. Moreover, its effects extended beyond the visual cortex, reversing the decline in gamma frequency coherence between the visual cortex and hippocampus and maintaining functional connectivity between the hippocampus and cortex. A significant increase in gamma frequency power was observed in the hippocampus.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}
- **Diseases:** neurodegenerative (MESH:D019636), trauma (MESH:D014947), inflammation (MESH:D007249), neuroinflammation (MESH:D000090862), surgical (MESH:D007431), AD (MESH:D000544), PND (MESH:D019965), dementia (MESH:D003704), amyloid (MESH:C000718787), executive dysfunction (MESH:D006331), retinal damage (MESH:D012164), Impairs Learning and Memory (MESH:D007859), neuronal degeneration (MESH:D009410), Cognitive Dysfunction (MESH:D003072), amyloid plaques (MESH:D058225), neuronal dysfunction (MESH:D009461)
- **Chemicals:** O2 (-), 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (MESH:C024286), paraformaldehyde (MESH:C003043), sucrose (MESH:D013395), isoflurane (MESH:D007530), bupivacaine (MESH:D002045), silver (MESH:D012834)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** C-25 C, C for 48-72

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12967628/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12967628/full.md

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Source: https://tomesphere.com/paper/PMC12967628