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

Foc.us v2 40hz tACS

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

Halo Neuroscience in the News

There’s been a lot of attention to the Halo Neuroscience device, much of it around use by olympic-level athletes. Halo Sport is a VC-backed tDCS device that targets the Motor Cortex. We’ve covered it previously elsewhere on the blog.

US Olympic track star out to prove Halo Sport headphones make him faster, stronger
The Brain-Zapping Olympians
Olympic Athletes Try Zapping Their Brains to Boost Performance

Sleep Spindles tACS and Memory Consolidation | Frohlich Lab

For the first time, UNC School of Medicine scientists report using transcranial alternating current stimulation, or tACS, to target a specific kind of brain activity during sleep and strengthen memory in healthy people.


Flavio Frohlich, PhD

Full Story: No dream: electric brain stimulation during sleep can boost memory
Paper: Feedback-Controlled Transcranial Alternating Current Stimulation Reveals a Functional Role of Sleep Spindles in Motor Memory Consolidation

Mind machines – the promise and problems of cognitive enhancement devices

In this video Roi Cohen Kadosh (Professor of Cognitive Neuroscience at the University of Oxford) likens the use tDCS without a task and purpose, to an athlete taking steroids and not exercising. He discusses recent papers coming out of his lab and describes the research that resulted in this paper: Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement. Kadosh points out that while tDCS did enhance performance in a math challenge, it simultaneously had a negative impact on another. Following Kadosh, Dr Hannah Maslen discusses DIY and DTC tDCS in the context of regulation in the EU.

Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

Understanding The Mechanism Underlying The Effects of tDCS

The paper, Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain, is being lauded as a major discovery among tDCS researchers. It is however, extremely hard to follow. Fortunately RIKEN also issued a press release describing the study in a way most tDCS-curious will understand. Read the full press release here.

Researchers at the RIKEN Brain Science Institute in Japan have discovered that the benefits of stimulating the brain with direct current come from its effects on astrocytes — not neurons — in the mouse brain. Published in Nature Communications, the work shows that applying direct current to the head releases synchronized waves of calcium from astrocytes that can reduce depressive symptoms and lead to a general increase in neural plasticity — the ability of neuronal connections to change when we try to learn or form memories.


(top) Low spontaneous calcium activity in a normal mouse followed by tDCS-induced calcium surges. (bottom) tDCS-induced calcium surges are absent in IP3 Receptor 2 knockout mice, indicating that the calcium surges originate in astrocytes, not neurons.
Note: The upper. ‘normal’ mouse brain vs. modified mouse brain, bottom. Watch near ticking clock when ‘spontaneous’ switches to ‘tDCS’.

Let’s put this in some context by having a quick look at astrocytes and glial cells. From 2-Minute Neuroscience

Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

In two sham-controlled experiments, we found that repeated daily prefrontal tDCS sessions over 5 several days could effectively modulate how non-depressed individuals self-assess their mood states. Results show that participants experienced less psychological distress from daily stressors, a well established cause in the establishment of a negative emotional state. We replicated this finding in an independent, randomized, double-blind experiment applying similar protocol and stimulation on 3 consecutive days.

anode over the left F3 10–20 position, cathode over the contralateral F4 position

anode over the left F3 10–20 position, cathode over the contralateral F4 position

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

Thync Announces Sleep Vibe

This is could be a game changer. Announced today on the Thync mailing list. New vibe available for download.

Today, after a full year of clinical sleep studies, we are thrilled to announce a sneak peek of our latest research.20160223thyncSleepAnnounced

After 1 week of using our new Good Night Vibe, our participants reported:

  • Improved sleep quality similar to 4 weeks of meditation or 8 weeks of melatonin
  • Reduced mid-night awakenings
  • Improved morning mood & alertness
  • Reduced anxiety & stress

…And the cherry on top?

The same Good Night Vibe that we used in our clinical testing is now available in the Thync app for you to use!

So go ahead – run your own sleep study: Try out the Good Night Vibe for a week, and let us know what you think!

 

Enhanced Training Through Neurostimulation | HRL Laboratories

What if becoming an expert pilot were as simple as putting on a cap?

That’s the lead-in line on the following video entitled: Enhanced Training Through Neurostimulation presented by HRL Laboratories.  (@HRLLaboratories)

The video is based on the Feb. 9, 2016 study, Transcranial Direct Current Stimulation Modulates Neuronal Activity and Learning in Pilot Training

The researchers featured in the video, post-docs Jaehoon Choe and Matthew Phillips work for HRL Laboratories. Did they know the PR dept. was going to take their interviews and inject them with awesome graphics and all sorts of hyperbole? Is it marketing capitalizing on research, or research capitalizing on marketing?

I plan to dig deeper into this story and update as more info emerges and I get a better understanding of the study.

Unlocking the Brain with New Stimulation Technologies | Medium

Excerpt from an interview with clinical neuroscientist, Kate Hoy. The paper referenced is Testing the limits: Investigating the effect of tDCS dose on working memory enhancement in healthy controls

What is the most surprising or interesting research case you have worked on?

The findings where the data doesn’t show what you expected are always the ones that mean the most. In one study we were looking at the effect of gentle electrical stimulation (tDCS) on memory in healthy people; we compared sham (‘fake’) stimulation with a low and a high dose of tDCS. My hypothesis was that the higher the dose the better would be the performance and I couldn’t have been more wrong. The findings showed that the sham stimulation did nothing (as predicted), the low dose improved performance significantly, and the high dose behaved most similar to the sham stimulation.

This puzzled us so we brainstormed the findings and came back to the idea of homeostasis, where you can push the healthy brain a little but if you push it too much it will ‘push back’. Essentially, there are only limited gains in brain function that can be achieved in the healthy brain. That finding, which was from an Honours project, that I had initially worried was uninterpretable, resulted in a publication, two current PhD projects, and set me off on a different path with this aspect of my research.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning

Great example of exactly what we’re up against. The study in the previous post found no effect on Working Memory in older adults targeting dorsolateral prefrontal cortex (dlPFC). This study did find a positive effect on Episodic Memory in older adults targeting left lateral prefrontal cortex (PFC).

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions like amnestic Mild Cognitive Impairment (aMCI) and Alzheimer’s Disease (AD). Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal tDCS over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen’s d effect size=1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as MCI.

No Significant Effect of Prefrontal tDCS on Working Memory Performance in Older Adults

Improved working memory is why many of us are interested in tDCS. Here’s another study showing no effect. Looks like a good study, though it’s a single-session of tDCS. Of late I’ve noticed more studies targeting working memory using the N-back test to measure. I’m hopeful a protocol will be discovered (i.e. a different montage, dosage, or perhaps tACS) that does improve working memory.

Transcranial direct current stimulation (tDCS) has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC) on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1mA and 2mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

Source: No Significant Effect of Prefrontal tDCS on Working Memory Performance in Older Adults

A technical guide to tDCS, and related non-invasive brain stimulation tools | Clinical Neurophysiology

Many of the leading tDCS researchers contribute to this Open Access article on clinical application of transcranial electrical stimulation (tES) techniques. Read it online, or download the pdf. (HatTip to Reddit user gi67)

  1. 1. Introduction
  2. 2. Transcranial direct current stimulation
    1. 2.1. Selecting and preparing electrodes and contact medium
    2. 2.2. Selecting and preparing electrode placement
    3. 2.3. Selecting a stimulation protocol
    4. 2.4. Use of blinding and sham
    5. 2.5. Safety versus tolerability
    6. 2.6. Considerations for transcutaneous spinal DC stimulation (tsDCS)
    7. 2.7. Considerations for cerebellar tDCS
      1. 2.7.1. Targeting the whole cerebellum
      2. 2.7.2. Targeting the cerebellar hemispheres
    8. 2.8. Selecting a stimulator
  3. 3. Transcranial alternating current stimulation (tACS)
    1. 3.1. Selecting tACS electrode placement
    2. 3.2. Selecting experimental design
    3. 3.3. Selecting stimulation parameters
    4. 3.4. Transcranial random noise stimulation (tRNS)
  4. 4. Monitoring physiological effects of tES
    1. 4.1. Monitoring physiological effects of tES with TMS
      1. 4.1.1. Monitoring of tES-induced motor cortex plasticity
    2. 4.2. Monitoring physiological effects of tES with electroencephalography (EEG) and event-related potentials (ERPs)
      1. 4.2.1. Selecting an approach
      2. 4.2.2. Integrating tES and EEG electrodes
      3. 4.2.3. Recording EEG during tES
    3. 4.3. Monitoring physiological effects of tES with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
      1. 4.3.1. Integration of tDCS with MR
      2. 4.3.2. Considerations for concurrent MR acquisition
      3. 4.3.3. Other considerations for tDCS integrated with MR
  5. 5. Monitoring functional effects of tES
    1. 5.1. Monitoring functional effects of tES in healthy subjects
    2. 5.2. Monitoring functional effects of tES in patients
  6. 6. tDCS/tACS/tRNS in animal preparations
    1. 6.1. DC-, AC-, RN-induced membrane polarization
    2. 6.2. What can we learn from in vitro experiments?
  7. 7. tDCS and models of electric current through the brain
  8. 8. tES ethics
    1. 8.1. Education and training
    2. 8.2. Settings and procedures
    3. 8.3. Patient/subject selection
    4. 8.4. Patient/subject education and informed consent
  9. 9. Concluding remarks
  10. References

Canadian study tests electrical stimulation to treat depression in pregnancy | CTV News

Update 12/16/2015: Bouncing this story up to the top again today because of news of a new study that links Autism to SSRI (anti-depressant) use in pregnant women.

The analysis also found that women who were prescribed more than one class of antidepressants during the last six months of pregnancy were more than four times more likely to have a child with autism, compared with women who did not take antidepressants while pregnant.

Update 10/16/2015: Today I learned that this study is ongoing and recruiting participants. If you or someone you know is pregnant and dealing with severe depression, consider contacting study author Simone Vigod at Women’s College Hospital in Toronto. Study Protocol. You can also follow Simone on Twitter.

Watch the video at CTV.
tdcsPregnantCTV

Tatania Samburova, a Russia-born economist who immigrated to Canada two years ago, developed depression before becoming pregnant. Her depression left her feeling hollow, even suicidal.

“You do not feel yourself living. You do not want anything, you do not want to go somewhere, to do something,” she said.

Her doctor offered her antidepressants, but, while she knew they would offer her relief, she decided against using them over fears they may harm her child.

“Even if it will bring me, right now, some kind of relief, it can also affect the life of a little child,” she said.

Instead, she travelled to Mount Sinai (hospital) every day for three weeks to be treated as part of the study. She doesn’t know for sure if she received a sham treatment or the actual tDCT stimulation but suspects she had the actual therapy because within days her appetite returned and she felt her mood lifting.

“This treatment brought happiness back to me; it brought life back to me,” she said.

She remains well today, with her baby due mid-March.

Vigod notes that some women are so desperate for treatment that they are not waiting for the study results.

“I can tell you anecdotally that women are buying devices like this in the U.S. and using them at home, but they haven’t really been tested to see if it works to make the depression better.”

via Canadian study tests electrical stimulation to treat depression in pregnancy | CTV News. HDCstim (device shown)

tdcsPregnantDepressionStudy

From the study protocol: The active tDCS intervention is active 2 mA tDCS. Direct current is transferred continuously for 30 minutes with a pair of saline-soaked sponge electrodes (contact area of 5 × 7 cm), and delivered by a specially developed, battery-driven constant current stimulator. The electrodes are placed over F3 and F4 according to the 10–20 international system for electroencephalogram placement.

Yes But What Do The Researchers Think About tDCS? | Nature

From a study published earlier this year that collected responses from 265 career scientists whose work involves tDCS.
Researchers’ perspectives on scientific and ethical issues with transcranial direct current stimulation: An international survey

Researchers’ assessment of the efficacy of tDCS in clinical and enhancement contexts. Data represents distribution of responses (%) for each category, see legend.

The cautious approach to use of tDCS is also reflected in the low ratings for efficacy of its use to enhance normal functions. The tDCS research community appears well aware of current limitations and the need for future research to address those. The appearance of enthusiastic articles in the media and online suggest that these cautious views are frequently not being communicated clearly to the public. Researchers must make their views about the limited evidence of safety and efficacy clearly when speaking with the media or communicating with the public.