ArticleNature protocols2018
Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load.
Article in Nature protocols, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review.Neuropsychology review · 2024Pooled it
- Home-Based Gamma Transcranial Alternating Current Stimulation in Patients With Alzheimer Disease: A Randomized Clinical Trial.JAMA network open · 2025Trial
- SSVEP phase synchronies and propagation during repetitive visual stimulation at high frequencies.Scientific reports · 2021Trial
- Photobiomodulation with 808 nm Laser Light Repairs Mitochondrial Integrity and Normalizes ROS, ATP, and Membrane Depolarization in Aβ-Exposed Primary Neurons in Alzheimer's Disease Model.International journal of molecular sciences · 2026Article
- Photobiomodulation for Photoreceptor Rescue in Retinal Disease: Mitochondrial, Redox, Vascular, and Translational Perspectives-A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- High intensity 40 Hz flicker improves amyloid pathology and cognition with autophagy in 3xTg mice.iScience · 2026Article
- Maintaining and regaining episodic memory in Alzheimer disease: a circuit-based perspective.Nature reviews. Neurology · 2026Review
- Audiovisual gamma stimulation restores hippocampal neurogenesis and neural circuit plasticity in aging mice.Molecular psychiatry · 2026Article
- Retinal Amyloid Clearance Enhanced by 40-Hz Light Flicker via MHC-II+ Microglia Regulation in Mice.Investigative ophthalmology & visual science · 2026Article
- Targeting glymphatic-associated pathways for Alzheimer's disease: a review of non-invasive modulation strategies, mechanisms, and emerging evidence.Frontiers in immunology · 2026Review
- Frequency-Specific Transcranial Photobiomodulation Elicits Complementary Glial Mechanisms for Neurovascular Protection and Amyloid Clearance in Alzheimer Disease.Cyborg and bionic systems (Washington, D.C.) · 2026Article
- [Effects of 40 Hz light flicker stimulation on hippocampal-prefrontal neural activity characteristics during working memory tasks in Alzheimer's disease model rats].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2025Article
- Review
- Brain-Wide Spatiotemporally Distinct Traveling Waves Drive Anxiety-Like Behaviors in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Non-invasive light flickering reinstates visual plasticity in adult mice via lipocalin 2.BMC biology · 2025Article
- Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia.Annual review of biomedical engineering · 2025Review
- Photobiomodulation modulates mitochondrial energy metabolism and ameliorates neurological damage in an APP/PS1 mousmodel of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Monitoring photobiomodulation of amyloid-β aggregation in 3D cultured cells using label-free nonlinear optical imaging.Biomedical optics express · 2025Article
- Innovations in noninvasive sensory stimulation treatments to combat Alzheimer's disease.PLoS biology · 2025Review
- Improvement of neuropsychological and cognitive functions in older adults through transcranial vibroacoustic stimulation: a double blind, randomized, comparative trial.Frontiers in aging neuroscience · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglia, the primary immune cells of the brain, play a key role in pathological and normal brain function. Growing efforts aim to reveal how these cells may be harnessed to treat both neurodegenerative diseases such as Alzheimer's and developmental disorders such as schizophrenia and autism. We recently showed that using noninvasive exposure to 40-Hz white-light (4,000 K) flicker to drive 40-Hz neural activity transforms microglia into an engulfing state and reduces amyloid beta, a peptide thought to initiate neurotoxic events in Alzheimer's disease (AD). This article describes how to construct an LED-based light-flicker apparatus, expose animals to 40-Hz flicker and control conditions, and perform downstream assays to study the effects of these stimuli. Light flicker is simple, faster to implement, and noninvasive, as compared with driving 40-Hz activity using optogenetics; however, it does not target specific cell types, as is achievable with optogenetics. This noninvasive approach to driving 40-Hz neural activity should enable further research into the interactions between neural activity, molecular pathology, and the brain's immune system. Construction of the light-flicker system requires ~1 d and some electronics experience or available guidance. The flicker manipulation and assessment can be completed in a few days, depending on the experimental design.
Indexed as
Identifiers
30072722What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.