_________________________
∗ Transgenic mice are genetically engineered to model Alzheimer’s disease.
† Aside from the more obvious reasons, medical researchers use mice in their research because rodents’ “genetic, biological and behavior characteristics closely resemble those of humans, and many symptoms of human conditions can be replicated in mice and rats.” (LifeSciences) Inferences made about humans based on mice studies are more accurate than you might expect. But the correlation is by no means perfect.
A New Understanding of Memory
Among other things, the experiments outlined here shine some light on the little understood process of memory. Memories, it seems, are not actually lost when forgotten. What is lost is access to the memory. Think of a secluded pool deep in the jungle, accessible by a single path cut through the forest. One morning you find the jungle has taken back the path; the trail is completely grown over and there is no indication that it was ever there. The pool still exists, but you can no longer get there.
You higher a guide who is familiar with this jungle and he hacks a new path through the jungle. It may be a new path, different from the original, but it get you to the pool.
This in itself prompts some interesting considerations concerning our understanding of memory disorders including certain dementia. If memories are in fact like the pool, then creating a new neural path to a lost memory can recover that memory. Flashing light therapy may do just that.
Now the Science Behind Flashing Light Therapy
In a post of 24 Mar 2016, We May Be Able to Find Memories Lost to Alzheimer’s, we touched on some research by Susumu Tonegawa, Tonegawa’s team at the Picower Institute at MIT, using a procedure called optogenetic stimulation, found that they could get mice to remember previously forgotten experiences.
To very briefly summarize, the experimental design used electric shock to create a fear response in transgenic mice. As expected, the lab-induced Alzheimer’s caused the mice to forget the experienced shock. They no longer exhibited a fear response when in the testing environment.
Now the scientists implemented an optogenetic procedure, aimed at cells in the hippocampus of these forgetful rodents. The hippocampus is the area in the brain responsible for memory, of turning experience into memories. With optogenetics the fear response returned! The mice remembered the training that Alzheimer’s had caused them to forget.
Like the guide hacking a new path through the jungle, it seems that the optogenetic procedure acted like a trailblazer in the brains of these mice, creating a new path to the memory of the electric shock. If optogenetics can create a new neural connection to memories, it stands to reason that it might play a role in Alzheimer’s treatment. Unfortunately, the treatment is very invasive. It involves drilling a hole through the skull to introduce a virus that makes targeted brain cells photo-sensitive. A fiber optic probe is then inserted into the brain to administer stimulation to those cells. As you might expect, the FDA frowns on using such procedures on human subjects.
This optogenetic procedure is not blinking light therapy, which is non-invasive.
With optogenetics scientists control brain activity with light
A detailed account of optogenetics is beyond the scope of this article. The procedure involves introducing light sensitive proteins into specific neurons, then stimulating those nerve cells with light. In this way individual groups of neurons can be studied in a Optogenetics is an exiting addition to science’s tools for exploring and understanding the brain. In fact, a team at MIT’s McGovern Institute for Brain Research were able to create false memories in mice using this technique.x If you are interested you can get more detailed accounts of optogenetics from Scientific American and on Wikileaks.
Aware of this research, a team headed by Li-Huei Tsai∗ also at MIT’s Picower Institute for Learning and Memory wondered if light stimulation could be administered in a less invasive manner. Professor Tsai’s group put transgenic mice into a dance club for one hour. Well, it wasn’t really a club but a box with a strobe-like light flashing at 40 times per second.
Light entering through the eyes will stimulate the visual cortex rather than the hippocampus, but these investigators were not attempting to influence memory producing neurons, but what we commonly call brain waves.
What are Brain Waves?
Brain waves are rhythms caused when neurons fire in groups. This synchronous firing is how different parts of the brain communicate. Different brain states (sleep, meditative, excited, contemplative, etc.) are each associated with a frequency range measured in Hertz (cycles per second). Lower frequencies correspond to more relaxed brain states. Gamma waves are at the highest frequency (38 to 42 HZ) and are present during normal waking activity. They are associated with thinking, memory, attention, spatial navigation, etc. The speed of the flickering lights used in the study (40 Hz) was selected to induce gamma waves in the brains of these mice.
After just an hour in the box the researchers found that the test mice had significantly reduced levels of Alzheimer’s plaques (amyloid-β) than a test group that didn’t get to party. “If humans behave similarly to mice in response to this treatment, I would say the potential is just enormous, because it’s so non-invasive, and it’s so accessible,” said Li-Huei Tsai. In other words, this study could result in the inexpensive, non-invasive, non-pharmacological treatment that we alluded to at the beginning of this article.
But how does a blinking light eliminate the hallmark plaques from the Alzheimer’s brain?
Normal neurons and neurons containing tangles and surrounded by Amyloid plaques. These plaques and tangles, the hallmarks of Alzheimer’s disease, are the proteins that, stimulated by flashing light therapy, the newly-voracious microglia clear out. ~Image credit Bright Focus Foundation
It appears there is a connection between gamma waves and a cellular structure called microglia. Microglia are immune cells that act as the garbage collectors of the nervous system, removing debris and dead cells and helping to control inflammation. AD somehow causes these cells to become inactive or ineffective, unable to keep the brain tidy and operating normally. Microglia in this impotent state might be considered to be another hallmark of Alzheimer’s disease.
The light blinking at a rate of 40 times per second stimulates gamma waves in the visual cortex, which in turn somehow modifies or transforms the microglia into what Professor Tsai calls “an engulfing state”. Responding to the flashing light therapy the microglia do their job and clear the brain of the debris that is at least partly responsible for damaging neurons and causing the symptoms we associate with Alzheimer’s disease.
And the surprises surrounding flashing light therapy just keep on coming. Another major hallmark of AD, the fibrillary tangles caused by misfolded tau protein disappeared as well, cleaned out by the now voracious microglia. Blood vessels in the brain enlarged to almost twice their previous size. Eight weeks of this treatment protected brain cells from dying and the team found that synaptic connections were being restored.
Perhaps the biggest surprise was the discovery that the effects of this seemingly simple treatment spread to other parts of the brain, including the hippocampus and the prefrontal cortex.
_________________________
∗ We have met Professor Tsai before; she is the researcher who helped Alzheimer mice remember a maze by putting them in a stimulating environment. Read more at Can We Remember Lost Memories?
Is Flashing Light Therapy Too Good to be True?
Now that I have laid it out it seems too simple to be a real solution. But Tsai’s team continues to get some remarkable results in the lab with her mice, and we are seeing some equally remarkable results with flashing light therapy and human subjects.
What does this mean? In the short term, it looks like we can slow, maybe even stop the progression of Alzheimer’s disease. For how long we don’t know. But we are also witnessing a marked improvement in memory and cognitive ability in as little as a week in our human subjects with Alzheimer’s.
A preliminary study assessed 24 individuals with AD diagnoses using two standardized cognitive scales, the MoCA Cognitive Assessment Test, the Mini-Cog™ Cognitive Impairment Exam; and a Subject Specific Life History (SSLH) exam, before and after administration of flashing light therapy. Following just seven days of treatment, the conclusion of this study was that:
All subjects exhibited improvement of cognitive function as expressed by testing with an average improvement of 73.6% across all exams. 92% of subjects were described as “improved” by their family and or caregivers, inclusive of “mood, disposition, and engagement” as defined in administration of a post therapy interview.
You can read the abstract of this study below in Related Research.
In the mice studies the affects of AD, the buildup of amyloid plaques and the ensuing memory and cognitive issues, return quickly if the treatment is stopped. We need more data to know if this is true of human subjects as well, but it will likely be. I, for one, would prefer have this non-invasive treatment for one hour everyday than to live with a diminishing cognitive ability.
Li-Huei Tsai explains flashing light therapy
Watch Li-Huei Tsai explain what she and her team at MIT have learned about the effects of flashing light and sound pulsing at 40Hz..
Related Research
Flashing Light Therapy for Alzheimer’s
- Susumu Tonegawa, et.al., Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature volume 484, pages 381–385 (19 April 2012).
- Susumu Tonegawa, et. al., (2015). Engram Cells Retain Memory under
Retrograde Amnesia. Science 348.6238 (2015): 1007–1013. - Li-Huei Tsai1, et.al., (2016). Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7; 540(7632): 230–235.
- Alexander I. Erofeev, et.al., (2015). The new method for studying neuronal activity: Optogenetics. St. Petersburg Polytechnical University Journal: Physics and Mathematics Volume 1, Issue 3, October 2015, Pages 256-263.
- Massachusetts Institute of Technology. (2015, May 28). Scientists retrieve lost memories using optogenetics. ScienceDaily. Retrieved July 25, 2018 from
- Anne Trafton, Unique visual stimulation may be new treatment for Alzheimer’s: Noninvasive technique reduces beta amyloid plaques in mouse models of Alzheimer’s disease. MIT News, December 7, 2016.
- Anne West, (20)Manipulating Memory through Optogenetics: A Conversation with Neuroscientists Xu Liu and Steve Ramirez. The Psych Report, June 28, 2014.
- Ashley Taylor, Toward Treating Alzheimer’s Disease with Brain Waves: In a mouse model, researchers mitigated three Alzheimer’s disease–associated symptoms by stimulating gamma waves with light. The Scientist, Dec 7, 2016
- B. Beshaw (2018). Effects of Specific Light Therapy for the Treatment of Cognitive Impairment Associated with Alzheimer’s Disease. Department of Memory Research, © 2018 Airgo LLC . Unpublished study reprinted at right.
Effects of Specific Flashing Light Therapy for the Treatment of Cognitive Impairment Associated with Alzheimer’s Disease
B. Beshaw 2018
ABSTRACT
OBJECTIVE:
The objective of this study was to compare the effect of specific flashing light therapy on the cognitive function expressed by individuals diagnosed with Alzheimer’s Disease-related cognitive impairment. Diagnoses were given according to the 9th and 10th version of the International Classification of Diseases (ICD-9 331.0, ICD-10 G30.9) as well as the 3rd revised and 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R, DSM-IV). The researchers were to additionally observe the influence of the different diagnostic components (memory impairment, personality changes, definition of other intellectual functions) on the prevalence of impairment and to record any expressions of confusion, discomfort, or possible interactions with existing individual subject therapies.
METHODS:
The study group comprised of 24 subjects fulfilling the defined diagnoses were interviewed and assessed for cognitive impairment via the MoCA Cognitive Assessment Test, the Mini-Cog™ Cognitive Impairment Exam, and a Subject Specific Life History (SSLH) exam, compiled with assistance of the subject’s family, caregivers and other available research for administration. After the application of a specific light therapy for equivalent duration the study group was again tested by administration of the three defined exams.
RESULTS:
Subjects average MoCA results improved from 15 out of 30, to 25.5 out of 30, for a 70% change.
Subjects average Mini-Cog™ results improved from 2 out of 5, to 4 out of 5, for a 100% change.
Subjects average SSLH results improved from 8 out of 15, to 12 out of 15, for a 50.9% change.
Notable observations were that the memory impairment component of the subjects was the most dramatically improved, followed by executive functioning.
CONCLUSION:
All subjects exhibited improvement of cognitive function as expressed by testing with an average improvement of 73.6% across all exams. 92% of subjects were described as “improved” by their family and or caregivers, inclusive of “mood, disposition, and engagement” as defined in administration of a post therapy interview.
Prevalence of dementia varied widely dependent on the diagnostic classification system used prior to our interview. Subjects
comprised those with evidence of both Primary Degenerative Dementia and Multi-Infarct Dementia inclusive of Posterior
Cortical Atrophy.
ICD-9 Protocol sourced at icd9data.com DSM-III-R Codes sourced at nimhgenetics.org
ICD-10 Protocol sourced at icd10data.com DSM-IV Codes sourced at behavenet.com
MoCA Montreal Cognitive Assessment at mocatest.org Mini-Cog™ Screening for Cognitive Impairment at mini-cog.com
Leave a Reply
Want to join the discussion?Feel free to contribute!
Leave a Reply
Organizations & Affiliations
Purple Angel Ambassador
Dementia Friendly America
This light therapy is so very exciting.
So very interesting. This could really help with this massive problem.
This iPhone app, Strobe Therapy, performs similarly to a Lucia Light.
https://apps.apple.com/ca/app/strobe-therapy/id1479351910
If you have a recent iPhone (I have an iPhone 11) try it and let me know if it is safe.
It produces amazing kaleidoscopic visual hallucinations when the flash is situations a few inches from the closed eyes.
Hi John. In a your August 24, 2018 response to Vicki’s question about flashing lights and seizures you said “Every precaution has been taken to ensure that the light used in our device is safe”. This makes it sound like you have a flashing light therapy product available. However, the only lighting product I can find on your site is the full spectrum light.
Do you have any flashing light therapy products available for purchase?
Thanks very much.
Just found this online. Is this company legitimate, do you Know?https://gammalighttherapy.com/?gclid=Cj0KCQiAtf_tBRDtARIsAIbAKe1S4FhLbdBPIYO4HRsg7s-i5pWSGYpzGbGm1MC-1Aef9yBaDbOo2zwaAtgpEALw_wcB
Hi Andrea – I can’t speak to the legitimacy of the company, but the research on which the therapy is based is sound. See https://best-alzheimers-products.com/alternative-therapy-for-alzheimers/flashing-light-therapy-for-alzheimers. The researchers who originated the studies have had success with both flashing light and pink sound to improve cognitive function in human subjects with Alzheimer’s disease. They have founded their own company, Cognito Therapeutics, at https://www.cognitotx.com/. They used goggles to deliver flashing light and pink sound to the eyes of subjects – I have a similar device that I am testing, informally as yet, that also show promise.
On the other hand, Cognito Therapeutics, as yet, have not make their device commercially available, so I would watch the progress there before putting too much into it. Also, goggles that deliver the light directly into the eyes show promise. I am not sure the delivery system used by Gamma Light Therapy, at least for the light, would be nearly as effective. My recommendation is to get on Cognito’s mailing list to follow the progress of this fascinating line of study.
Even though it would be premature, are there products on the market now that use light and sound therapy?
Hi Brian – as far as I know there is nothing yet on the market that incorporates both. There is a product called GliaGoggles with flashing light therapy alone that has shown some promise in initial testing. However,I am no longer able to find it on line. Marketing a product like this is very difficult, however paradoxical that seems to be. Li-Huei Tsai at MIT who did the original studies that support the potential of flashing light therapy for Alzheimer’s developed a goggle/device that combines flashing light and pink noise at Hz. She, too, reported some amazing results in trials, but her device also in not available commercially. I find it hard to understand why, given the success of trials, nothing is yet available.
I would be concerned this will cause a seizure. It is already well known that the flashing light (strobe) causes seizures. It also causes nausea.
Hi Vickie – The type of flashing light that can potentially cause seizures is very different, both in color and flash rate. Every precaution has been taken to ensure that the light used in our device is safe. Color and blink-rate are not in the range that is worrisome.
No, Flashing and flickering lights don’t cause seizures. It’s only a problem in people who are prone to seizures. People who suffer from epilepsy should not use these products.