40 Hz, gamma and the brain
The 40 Hz idea comes from mouse experiments at MIT in which light flickering 40 times a second, and later 40 Hz sound, reduced Alzheimer's-type protein build-up. Two independent laboratories have since failed to reproduce the core findings, and human studies so far are small feasibility trials that did not change standard measures of cognition. There is no evidence that listening to 40 Hz audio protects or improves a healthy brain.
Where the idea came from
In 2016 a team led by Li-Huei Tsai reported in Nature that driving 40 Hz gamma rhythms in mice bred to develop Alzheimer's-type pathology reduced amyloid-β and changed the behaviour of the brain's immune cells [1]. A 2019 paper in Cell extended this to 40 Hz sound and to sound and light together, with improvements on mouse memory tasks [2]. The approach is called GENUS, for gamma entrainment using sensory stimuli. Read the summary.
What happened when others tried it
- A 2023 study in Nature Neuroscience found that 40 Hz flicker did not entrain native gamma rhythms in the mouse cortex or hippocampus, produced no significant change in amyloid or immune cells, and that the mice found the flicker aversive [3].
- A second group ran five weeks of flicker at 24, 40 and 80 Hz and found no reduction in amyloid [4].
- A human feasibility study in 15 people with mild probable Alzheimer's found some imaging signals, while standard cognitive scales did not move. It was not designed to test whether the treatment works [5].
- In people, flicker at 34–38 Hz drove stronger gamma responses than 40 Hz in one study, so 40 may not even be the best number [6].
Read the summary of the replication attempts.
What about 40 Hz binaural beats?
A 40 Hz binaural beat is a different thing from the stimulation used in those experiments, which was flickering light or a train of clicks. Above about 30 Hz most people stop hearing a binaural beat as a beat at all. One small study found that 40 Hz beats made attention more narrowly focused on a visual task [7]; that is the extent of the evidence.
A note on flicker
Flickering light can trigger seizures in people with photosensitive epilepsy, with the greatest risk at around 15 to 25 flashes a second. Anyone with a history of seizures should avoid flicker devices unless a clinician says otherwise.
Questions people ask
- Does 40 Hz sound help with Alzheimer's?
- It is unproven. Early mouse studies were promising, two independent labs failed to replicate them, and human trials so far are small and did not change standard cognitive measures.
- Do 40 Hz binaural beats increase gamma waves?
- There is no good evidence that they do. The research on 40 Hz used flickering light and pulsed sound, not binaural beats, and binaural beats are hard to perceive above about 30 Hz.
- What is GENUS?
- Gamma entrainment using sensory stimuli: a research approach from MIT that uses 40 Hz light flicker and sound to try to drive gamma rhythms in the brain.
- Is 40 Hz light safe?
- Flicker can provoke seizures in people with photosensitive epilepsy. In healthy people it is generally tolerated, but anyone with a seizure history should avoid it unless advised by a clinician.
Sources
- Iaccarino, H. F., Singer, A. C., Martorell, A. J., et al. (2016). Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature, 540(7632), 230–235. doi.org/10.1038/nature20587
- Martorell, A. J., et al. (2019). Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition. Cell, 177(2), 256–271. doi.org/10.1016/j.cell.2019.02.014
- Soula, M., et al. (2023). Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer's disease model mice. Nature Neuroscience, 26, 570–578.
- Yang, X., & Lai, H. C. (2023). Chronic LED flicker at 24/40/80 Hz failed to reduce amyloid-β in 5XFAD mice. eNeuro.
- Chan, D., Suk, H.-J., et al. (2022). Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: results of feasibility and pilot studies. PLOS ONE, 17(12), e0278412.
- Lee, K., et al. (2021). Optimal flickering light stimulation for entraining gamma waves in the human brain. Scientific Reports, 11, 16206.
- Colzato, L. S., Barone, H., Sellaro, R., & Hommel, B. (2015). More attentional focusing through binaural beats: evidence from the global–local task. Psychological Research, 81(1), 271–277.