Can stimulating your nervous system reverse Parkinson’s, reduce depressive episodes, and help you learn the piano?

In the past 100 years, we’ve made great advances of measuring and understanding the brain. Researchers and doctors have harnessed this knowledge to reverse the symptoms of Parkinson’s, decrease depressive episodes, help athletes run faster — and many other advancements we believed were only possible in science fiction. Now, many of these devices are making their way into our homes. Are we ready?

This is Part 2 in the series. In Part 1 of this series, we looked at monitoring brain activity. Now, we’ll dive into technologies to repair and improve brain function.

Walking out of the NYC Neuromodulation 2017 conference this past January, I realized that humanity is hitting an inflection point with our understanding of the human brain and how to improve or repair it.

Neuromodulation, alteration of nerve activity often achieved by delivering electric stimulation, has existed since the early 1960s, when Neurosurgeon C. Norman Shealy started experimenting with deep brain stimulation (DBS) to provide relief of intractable pain in a patient. In the past 60 years, science has greatly advanced these technologies and they are slowly making their way out of academia and the clinic into the home.

So, what can neuromodulation do?

Many patients and clinicians in the medical community are looking for non-pharmacologic treatments for common neuropsychiatric disorders like major depression, chronic pain, and epilepsy. DBS has been shown to treat symptoms of Parkinson’s disease. Transcranial Magnetic Stimulation (TMS) has been approved by the FDA to treat depression and migraines.

Neuromodulation techniques have become increasingly popular in both research and clinical facilities, and the FDA has approved techniques for a wide range of conditions including epilepsy, migraines, OCD, and Parkinson’s.

NPR’s Invisibilia podcast “Frame of Reference”

We are only at the beginning of understanding what this technology can do for us. NPR’s Invisibilia produced a haunting podcast this past summer called “Frame of Reference” on the story of Kim, a physician with Aspergers (worth listening to when you get an hour!). Kim participated in a research study using TMS to see if she could develop emotional and social cues in the same way that neurotypical people do. After the treatment, she felt that her “world was transformed, for better and worse, at age 54 by a brief encounter with a powerful magnet.”

John Elder Robison wrote a similar piece in the NYT how an experimental autism treatment using TMS changed his life — and “cost him his marriage” when he was able to process emotional connections that previously evaded him.

Not all the use-cases for neuromodulation are clinical. With neuromodulation, it seems that we have a chance to push human potential — but how far? DARPA has been using transcranial direct current stimulation (tDCS) on military personnel. Snipers using tDCS devices have cut their learning curves in half. Start-ups are also looking to bring human potential advancements to civilians. Halo Neuroscience is using tDCS to improve athletic performance in Olympians.

It’s early days and nearly all of these use-cases are unproven. But as more investment comes into this industry and as more controlled experiments are run, we will likely have more options to improve and repair the brain that do not require pharmaceuticals.

So, what exactly is neuromodulation?

No drugs. Just magnets and electric currents. Photo Cred: Boston Children’s Hospital Blog

Neuromodulation, as defined by The International Neuromodulation Society, is the “alteration — or modulation — of nerve activity by delivering electrical or pharmaceutical agents directly to a target area.” Neuromodulation is an evolving therapy that can include:

  • Using a range of electromagnetic stimuli (e.g., transcranial magnetic stimulation or TMS)
  • Delivering a low current to the targeted brain area (e.g., transcranial current stimulation or tCS)
  • Instilling a drug directly in subdural region (e.g., intrathecal drug delivery)
  • Introducing genes or gene regulators and light (e.g., optogenetics)

Often neuromodulation methodologies are categorized across two axes:

  1. How focused is the treatment?
  2. How invasive is it?
Categorization developed by Dr. Zhi-De Deng at the Duke University School of Medicine

Of the methodologies, TMS is the most well-known and has a series of FDA and CE (European Union) approvals for a range of use-cases. Because TMS requires strong and large magnets to produce the pulse, TMS devices are large, expensive and generally only found in research or clinical settings.

Transcranial electrical stimulation (TES) is a form of neurostimulation which uses low current delivered to the brain area of interest via electrodes on the scalp. Because TES uses electrical current rather than magnets, TES devices are smaller and cheaper and are more likely to end up in a consumer’s home.

There are multiple types of TES, including:

  • Transcranial direct current stimulation (tDCS), the most popular type, is the application of weak electrical currents (1–2 milliAmp) and to modulate the activity of neurons in the brain. Because the electrodes are placed on the scalp, much of the current is shunted through the skin and within the brain, having a relatively small and diffused impact on the neurons. tDCS has been used for a range of conditions including Parkinson’s, cerebral palsy, MS, consciousness disorders, addition and craving, autism, attention disorders among others. For more details, skim recently published comprehensive database of published tDCS clinical trials (2005–2016). No tDCS devices have been approved by the FDA.
  • Transcranial alternating current stimulation (tACS) is a new and relatively unstudied approach to noninvasive electrical stimulation. tACS seeks to interfere with the brain’s cordial rhythms, which are “the apparently inherent rhythmic electrical oscillations taking place in the brain in the absence of evident external stimulation” (Source: M&W). Currently tACS studies focus on mood-related disorders, including depression and anxiety. Researchers are also looking into using the technology for addicts in rehabilitation and for stroke and brain trauma
  • Transcranial random noise stimulation (tRNS) is the newest and least-studied technique in non-invasive brain stimulation. tRNS is a special form of tACS, and applies various forms of noise during the session (e.g., often 100–640 Hz zero-mean Gaussian white noise). It’s designed to have the benefits of tDCS (e.g., neuronal excitation) without as many of the downsides (e.g., burning and possible seizures).

Deep drain stimulation (DBS) is most famously used for Parkinson's. It has also been applied in cases of essential tremor, primary dystonia, severe OCD, treatment resistant depression, epilepsy, traumatic brain injury and Alzheimer’s. Kernel, a start-up in California, is building advanced neural interfaces to treat disease. They are using DBS technologies to test their initial products. Long-term, Kernel seeks to develop the world’s first neuroprosthesis for cognition.

Other types of neuromodulation include spinal cord stimulation (SCS), most often used for chronic and neuropathic pain and spinal cord injury, vagus nerve stimulation (VNS), used for epilepsy, tinnitus, treatment-resistant depression, heart failure syndrome, migraine and obesity, and peripheral stimulation, which has been used for assisted breathing and wide range of other conditions.

Lessons from Neuromod 2017

Yannick Roy and I both attended the NYC Neuromodulation 2017 conference this past January. Check out Yannick’s NeuroTechX blog post on the conference, presenters, demos and themes.

Two major themes struck me at the conference that will impact the development of neuromodulation technologies:

Clinicians vs. Researchers

Clinicians and researchers at the conference often disagreed when it was time to take the lessons out of the lab and apply the technologies more broadly with a greater number of people.

Both TMS and TES apply relatively “non-focal” stimulation — when compared to focused treatments like deep brain stimulation. Both stimulate large sections of the brain and the subject-to-subject variations are large. Although most (but not all) researchers believe that non-invasive brain stimulation has a neurophysiological effect on the brain, the effects are at a group-level and it’s difficult to ascertain and predict what the stimulation is doing to individual neurons.

Because there is a lot of variability across non-invasive brain simulation research, many researchers at the conference wanted to do more work to understand how and why these techniques worked. Researchers were also worried that proven technology would be labeled as “snake oil” if it was not used properly.

On the flip side, many clinicians were eager to get them into their patient population, particularly for those who treated treatment-resistant depression. The clinician argument was focused more on the positive outcomes even if we don’t yet know why they occur. This tension between when the technology is ready for broader consumption will define much of the neuromodulation innovation over the next decades.

“At-home” vs “Do-It-Yourself”

There was a great deal of debate at the conference around using tDCS outside of the lab:

  • “At-home” tDCS, defined as clinical trials conducted by professional researchers often on participants (generally) with brain disease versus
  • “DIY” tDCS, defined by non-professionals using the technology at home often for enhancing function.

Although “DIY” tDCS was overwhelmingly cautioned against at the conference, “at-home” tDCS is becoming more popular with researchers — with good reason. It’s difficult to recruit participants to come into a lab, multiple times per week over many weeks to administer tDCS. The drop-out rates in studies were very high. At-home promises higher retention in studies, and a more natural environment for tDCS.

The question then became: how do we set up these trials? What’s the correct electrical dose to give the participant? How do we regulate the dose? How will the participant set up their electrodes?

Researchers are developing new protocols, devices, and software platforms the assist in the administration. At-home trials will not only lead to greater participation, but also allows researchers to scale their work to more people and we’ll have better results over time as we understand what works and what doesn’t. These advancements will likely bleed over into the DIY movement, too.

I’m interested in learning more about DIY: what’s the at-home landscape?

Although DIY non-invasive brain stimulation and “brain hacking” been covered in publications like Scientific American, The Economist, and Nature, and has risen in popularity, brain stimulation has its share of legitimate controversy.

This past summer, 39 researchers signed an editorial in the Annals of Neurology addressed to the DIY community listing out effects, concerns and unknowns when self-administering tDCS. It’s worth a read if you’re looking to experiment with this (unregulated) technology — and provides some food for thought to determine f you’re comfortable with these risks. For those curious from a personal perspective, I have limited my use of the technology given its current state.

When diving into DIY tDCS, it’s helpful to have a high BS meter. Companies can skirt around FDA regulations by making vague marketing statements while avoiding health claims. As outlined in the editorial, the downsides from tDCS can go beyond burning your scalp.

Here’s a few companies who have created consumer-oriented devices:

  • Foc.us has multiple devices stimulators and headsets starting at $99. While the company does not make claims about its devices it states that “tDCS has been proven to enhance alertness, boost focus and increase capacity to learn.” Foc.us sells a “closed loop system,” meaning that the tDCS devices is paired with an EEG that can detect brain-wave band changes and the stimulation can adapt based on the readings from the EEG.
Foc.us Headset
  • Halo Neuroscience focused on athletes. It doesn’t use the term tDCS anywhere on it’s marketing materials, instead focusing on “neuropriming.” Halo sells “first-ever headset that stimulates the part of your brain responsible for muscle movement. This accelerates training improvements in strength, endurance, explosiveness, and muscle memory.” Halo has partnered with Olympic athletes and the US military.
Halo Sport.
  • Thync promotes itself as “the first technology that actively changes the way you feel” and it works by “by gently stimulating nerves on the head and neck with safe, low level electrical pulses.” The original Thync Kit is “sold out” and the “Thync Relax Pro” focused on “sleep” and “relaxation” Spring 2017.

All of the above companies use “dry” electrodes, meaning the electrodes do not use gel or a saline-based contact to the scalp. Hackers looking for more customized set-ups buy their own brain stimulators and will pair them with DIY electrodes. Reddit’s r/tdcs channel has nearly 10k subscribers who are testing out do-it-yourself (DIY) tDCS.

Notably, one brain-stimulating device, the Fisher Wallace Stimulator has been approved the FDA for treatment of depression, anxiety, insomnia and chronic pain. The stimulator uses tACS and works by “generating gentle electrical pulses at patented frequencies that stimulate the brain to produce serotonin and other neurochemicals required for healthy mood and sleep.” In contrast, as of today, no tDCS device has been cleared yet by the FDA.

What about the ethical implications of this technology?

We may be able to repair and improve the brain with this technology — but should we? In a future blog post, we’ll share a few ways to think about this human-led evolution and the questions we should ask as we shape a future that we want — and not an accidental one.

If you’d like to stay up-to-date on this technology, there’s a few people in the industry worth following on Twitter. Melanie Segado (@sciencelaer), PhD candidate at McGill University, is a guru of all things neuromodulation. Check out more in-depth reviews of in Neurogadget. Anna Wexler (@anna_wexler), a PhD at MIT also writes about the growing DIY movement. Rachel Wurzman (@neuromemetic), a post-doctoral research fellow in the LCNS at the University of Pennsylvania, focuses on non-invasive brain stimulation techniques.

Do you have a favorite neuromodulation device? Share it here in our Google survey and we’ll share the results back once we have a collection of responses.

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