Gamma Waves Enhance the Brain’s Immune System to Treat Mice with Alzheimer’s disease.

Foc.us v2 40hz tACS

[Update 3/18/19] Exciting news in the fight against Alzheimer’s!
Dr. Tsai has a new lab. Tsai Laboratory

In the new study, researchers added acoustic stimulation that pulsed at the same frequency as the visual stimulation. And when mice — which were bred to develop Alzheimer’s-like symptoms — were exposed to both, researchers saw that the neurons in several of their brains’ key memory circuits chimed in and began humming along at exactly the same frequency.
What came next was remarkable and unexpected, even to the authors of the study.
In the wake of the sound and light sessions, an army of newly energized immune cells descended on several areas of the treated brains, including those most affected by dementia. Then they set to work with a vengeance on some neglected housecleaning.

LA Times https://www.latimes.com/science/sciencenow/la-sci-sn-alzheimers-brain-waves-20190315-story.html
Auditory stimulation combined with light-induced gamma oscillations in the hippocampus CA1 and auditory cortex regions of the brain reduces amyloid levels and improves memory in animal models of Alzheimer’s disease.
What does 40 Hz sound like? via NYT

A Possible Alzheimer’s Treatment With Clicks and Flashes? It Worked on Mice (NYT)
Light and sound stimulus therapy generates a buzz in Alzheimer’s research world (LAT)

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[Update 2/3/18] Nature reports on updates since the information about the research first emerged. How flashing lights and pink noise might banish Alzheimer’s, improve memory and more
——— Original article
I was first alerted to the story from a December 7 article in the Guardian, “Strobe lighting provides a flicker of hope in the fight against Alzheimer’s“. Researchers from the Picower Institute for Learning and Memory at MIT, working with (let’s call them) ‘Alzehiemer’s mice’, had discovered that flashing a light at 40hz (on-off at 40 times per second) increased gamma wave oscillations in the brain which led to the reduction of Amyloid beta (think, plaque) through the activation of microglia ‘clean-up’ immune cells. Here, let them explain it!


The paper, Gamma frequency entrainment attenuates amyloid load and modifies microglia makes clear that the light-flickering affected the visual cortex, which makes sense, as the light reaches the brain through the eyes. But wait, thinks I, what about tACS (transcranial Alternating Current Stimulation)… haven’t I seen numerous papers implying the ability to ‘entrain’ brain waves with tACS? What if you could increase 40hz Gamma in other parts of the brain? (Google Scholar Search: transcranial alternating, entrain, gamma)
But then I discovered that Radiolab just covered this exact story and it’s totally amazing! Really a must listen. So fun to hear the researcher’s amazement at this accidental (sort of) discovery!
So what’s with the photo of the Foc.us v2 device set up for a 40hz tACS session? Just that…

More about The Picower Institute for Learning and Memory at MIT

tDCS Boosts Synaptic Plasticity and Memory In Mice via Epigenetic Regulation of Bdnf Expression

Wait! There’s a Science Daily version.
Brain boost: Research to improve memory through electricity?

More important, the researchers identified the actual molecular trigger behind the bolstered memory and plasticity–increased production of BDNF, a protein essential to brain growth. BDNF, which stands for “brain-derived neurotrophic factor,” is synthesized naturally by neurons and is crucial to neuronal development and specialization.

“While the technique and behavioral effects of tDCS are not new,” said ONR Global Associate Director Dr. Monique Beaudoin, “Dr. Grassi’s work is the first to describe BDNF as a mechanism for the behavioral changes that occur after tDCS treatment. This is an exciting and growing research area of great interest to ONR.”

The research is sponsored by the Office of Naval Research!
What he said!

Podda, M. V. et al. Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression. Sci. Rep. 6, 22180; doi: 10.1038/srep22180 (2016).

I won’t even pretend to understand this paper at this point, but it’s unique enough that I want to encourage people to have a look. That said… what I think it’s saying is that (in mice) hippocampal tDCS creates a chain reaction that results in increased brain plasticity, i.e. increased neuronal connection which in this case is responsible for increased performance in a memory task. (Not more neurotransmitters.)

But this paper suggests the actual mechanism for how this is happening.

We hypothesized that anodal tDCS induced membrane depolarization mimicking neuronal activation and triggered epigenetic changes at Bdnf, thus favoring its transcription.

All together these results indicate that Bdnf expression in the hippocampus is induced by anodal tDCS and that enhanced acetylation at Bdnf promoter I is likely responsible for such effect.

Collectively, these data suggest that anodal tDCS induced epigenetic changes at Bdnf promoters likely relying on a mechanism involving CREB activation, CBP recruitment and H3K9 acetylation.

These results strongly support our hypothesis that increased histone acetylation promoting Bdnf transcription plays a major role in anodal tDCS-induced enhancement of synaptic plasticity.

tDCS-Model of anodal tDCS-induced chromatin remodeling

Scientists retrieve lost memories using optogenetics

I’m exposing my bias here, which is the hope that tDCS will be found to facilitate memory retrieval. This study, in mice, retrieved dormant memories using light (optogenetics) to activate cells used in memory formation. Recent studies suggest that memories are formed within a synaptic network, parts of which extend to areas of the brain more frequently targeted by tDCS. Probably closest to the research I’d like to see done (that I’m aware of) was reported in 2009, “Where Are Old Memories Stored in the Brain?“. I imagine a study where early memory, triggered by photos and recollections, are imaged using fMRI and that later, those same areas are targeted using tDCS. In the study reported on above, Medial Temporal Lobe Activity during Retrieval of Semantic Memory Is Related to the Age of the Memory, researchers concluded that older memories associated with regions in the frontal lobe, temporal lobe, and parietal lobe. (Though seems inconclusive as to whether memories are ‘stored’ there… “An additional way to understand the increasing involvement of some cortical areas, especially frontal cortex, as time passes is that older memories require more strategic, effortful search.”) Now, back to the post title article…

The researchers then attempted to discover what happens to memories without this consolidation process. By administering a compound called anisomycin, which blocks protein synthesis within neurons, immediately after mice had formed a new memory, the researchers were able to prevent the synapses from strengthening.

When they returned one day later and attempted to reactivate the memory using an emotional trigger, they could find no trace of it. “So even though the engram cells are there, without protein synthesis those cell synapses are not strengthened, and the memory is lost,” Tonegawa says.

But startlingly, when the researchers then reactivated the protein synthesis-blocked engram cells using optogenetic tools, they found that the mice exhibited all the signs of recalling the memory in full.

“If you test memory recall with natural recall triggers in an anisomycin-treated animal, it will be amnesiac, you cannot induce memory recall,” Tonegawa says. “But if you go directly to the putative engram-bearing cells and activate them with light, you can restore the memory, despite the fact that there has been no LTP.”

Source: Scientists retrieve lost memories using optogenetics
See Also: Neuroanatomy of memory
Gone But Not Forgotten? The Mystery Behind Infant Memories
The Hippocampus and episodic memory
(video)
Neuron Basics (video)

Magnets Can Improve Your Memory | TIME


Though TMS not tDCS, it would be interesting to see the original paper (Targeted enhancement of cortical-hippocampal brain networks and associative memory – paywall). My understanding is that the hippocampus is a difficult target for tDCS. But perhaps insights from this study could lead to ideas for a ‘memory enhancing’ tDCS montage.

To test this, Voss and his team of researchers had 16 healthy adults between the ages of 21 and 40 undergo MRIs so the researchers could learn the participants’ brain structures. Then, the participants took a memory test which consisted of random associations between words and images that they were asked to remember. Then, the participants underwent brain stimulation with TMS for 20 minutes a day for five days in a row. TMS uses magnetic pulses to stimulate areas of the brain. It doesn’t typically hurt, and has been described by some as a light knocking sensation. The researchers stimulated the regions of the brain involved in the memory network.

Throughout the five days, the participants were tested on recall after the stimulation and underwent more MRIs. The participants also underwent a faked placebo procedure. The results showed that after about three days, the stimulation resulted in improved memory, and they got about 30% more associations right with stimulation than without. Not only that, but the MRIs showed that the brain regions became more synchronized by the TMS.

via Magnets Can Improve Your Memory | TIME.