Big reversal: 40Hz light therapy may not work for Alzheimer’s disease

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Big reversal: 40Hz light therapy may not work for Alzheimer’s disease

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“Nature Neuroscience”: Big reversal: 40Hz light therapy may not work for Alzheimer’s disease.

Scientists found that 40Hz could not activate brain gamma waves, and the activity of Aβ plaques and microglial cells did not change.

At the moment when new drugs for Alzheimer’s disease (AD) have been repeatedly defeated, it is not an exaggeration to say that this non-invasive, safe and seemingly super-effective new  40Hz black technologytherapy is hot (simply put, the number of readings can be increased by 100,000!)

However, on March 07, 2023, a new paper published  in “Nature Neuroscience” undoubtedly casts a cold water on this technology. it turns out! The results of this paper show that 40Hz light does not induce gamma waves in the brains of mice with two AD models, nor does it clear amyloid beta (Aβ) in the brains of mice!

Researchers from New York University pointed out in the paper that 40Hz light stimulation may not be an effective mechanism for regulating the activity of deep brain structures , at least as far as the diverse pathological manifestations of AD individuals are concerned, it may not be a method that can work universally.

Paper screenshot

In short, judging from the information disclosed so far, 40Hz sound and light stimulation is really a promising new therapy!

However, if we study light stimulation and brain activity in depth, we will find that how many frequencies of light can actually cause what kind of brain activity is not uniform in past papers.

So what is the actual situation?

The researchers chose APP/PS1 and 5xFAD, two commonly used mouse models of AD, and tested the effect of 1-hour 40Hz light stimulation in a total of 6 groups of mice at different pathological stages . Mice in the control group were not given light or received continuous light.

The results of measuring Aβ deposition in neocortical brain regions such as visual cortex (V1) and hippocampus showed that although the average value of the data of mice in the experimental group was smaller, it did not achieve statistically significant differences from the control group .

40Hz photostimulation failed to affect Aβ deposition

Plaque deposition in the brains of experimental and control mice

The researchers analyzed the activity of microglia in several of these groups of mice and found no significant changes, either. Comparing various physiological parameters of microglia before and after light stimulation, no effect of light stimulation was found.

But it is worth noting that analyzing each group separately reveals that one group of 40Hz light stimulation did show a very significant therapeutic effect, which is comparable to the data provided in the paper published by Cai Lihui’s team in 2016.

The researchers believe that this may be affected by the high variability of Aβ plaques. It can be observed in different cohorts, ages, sexes, and transgenic animal models that there is a huge variability in Aβ plaque burden, and even within the same tissue structure, there are differences over time.

It can be seen that the effect of 40Hz light stimulation in the second group is significant

The researchers also tested the effects of long-term 40Hz light stimulation in 7-month-old 5xFAD mice and failed to observe significant changes after 1-hour daily exposure for 7 days.

Previously, the mechanism given by Cai Lihui’s team believed that 40Hz light stimulation works by stimulating gamma waves in key brain areas such as the visual cortex and hippocampus.

Unfortunately, in this study, the researchers did not observe that 40Hz can activate the neurons of both to produce gamma waves .

In fact, only a few cells can produce certain changes in response to 40Hz light stimulation.

Only a few neurons in the visual cortex (V1), hippocampus CA1, and entorhinal cortex (EC) responded to 40 Hz photostimulation

Brain Imaging Before and After 40Hz Light Stimulation

Aβ (green), microglia (red)

In addition, mice apparently do not love 40Hz light stimulation. The researchers found that the mice had obvious avoidance and aversion to the 40Hz light stimulation environment, which may be related to the increase in the activity of cholinergic receptors in the hippocampus caused by light stimulation.

The results of the experiment, which were completely opposite to those of Cai Lihui’s team, made things a little unclear. However, Qidian Cake thought about it optimistically.

It seems that 40Hz is not a universally effective treatment method, but at least it is not harmful at present, and the cost is not too expensive.

If you have the opportunity to try it, just in case It is effective, and it can be regarded as profitable…

I really want to see how you neuroscience experts comment on the results of this study, especially what Teacher Cai has to say (and why there is no news about your third issue) , if there are any wonderful comments recently, let’s talk about it later!

References:

[1]Soula, M., Martín-Ávila, A., Zhang, Y. et al. Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer’s disease model mice. Nat Neurosci (2023). https://doi .org/10.1038/s41593-023-01270-2

Big reversal: 40Hz light therapy may not work for Alzheimer’s disease

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