Director’s Innovation Speaker Series: Beyond the Lab: Navigating Ethical Challenges of Emerging Neurotechnology

Transcript

SHELLI AVENEVOLI: Good afternoon, everyone. Welcome to the NIMH Innovation Speaker Series. We're gonna wait just a minute as people join the webinar.

Good afternoon, everyone. We're just watching the numbers, waiting just a few more seconds for people to join the meeting. We're excited to have you here today. It looks like numbers are slowing down. So, I just want to welcome everyone to the NIMH Directors Innovation Speaker Series, and we're welcoming Dr. Anna Wexler today. She'll present on Beyond the Lab: Navigating Ethical Challenges of Emerging Neurotechnology. I think we have some initial points to make.

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Back to you, Dr. Avenevoli.

SHELLI AVENEVOLI: Thanks so much. So again, welcome to those just joining. We're really excited today to have Dr. Anna Wexler with us to present our Innovation Speaker Series. Again, the title of her talk is Beyond the Lab: Navigating Ethical Challenges of Emerging Neurotechnology.

Dr. Anna Wexler is an Assistant Professor of Medical Ethics at the University of Pennsylvania Perelman School of Medicine, where she studies the ethical, legal and social issues surrounding emerging health technology, with a particular focus on neuroscience applications. Dr. Wexler is the recipient of a 2018 NIH Director's Early Independence Award and a senior fellow at the Leonard Davis Institute for Health Economics. She received her Ph.D. from MIT in the history, anthropology, science, technology, and society program, where her dissertation was on the do‑it‑yourself brain stimulation movement.

Her essays have been published in outlets such as the New York Times, the Washington Post, Boston Globe, Slate, and STAT. And prior to her Ph.D., Dr. Wexler worked as a documentary filmmaker and science writer. She co‑directed and co‑produced the featured documentary film called Unorthodox.

So today we're actually going to hear a pre‑recorded preparation from Dr. Wexler. She is recovering from some health issues; so, she wanted to pre‑record that for us. However, we're very fortunate that she's also here today. So, she will be here to answer your questions. So don't forget to put those in the Q&A function below during the talk.

Thank you, and welcome.

(Video presentation)

ANNA WEXLER: Good afternoon, everyone. I'm very pleased to be here today. I'm gonna be recording this talk in advance, but I will be present for the live Q&A. So, I'm going to go ahead and share my screen.

Okay. So, my talk today is called Beyond the Lab: Navigating Ethical Challenges of Emerging Neurotechnology. So, what do I mean when I say, "beyond the lab"? Well, when most people think about science and medicine, they conceive of them as being conducted inside the laboratory or activities that stay within the boundaries of a hospital or clinic, and I think a lot of people have this sort of idealized conception of when and how advances in basic science in the laboratory should move beyond the laboratory and translate to treatments and therapeutics.

So, you're probably familiar with some version of this flow chart. This one is specifically about the pathway for medical devices, but in principle there's a similar pathway for drugs and biologics, where you have discovery and ideation, invention and prototyping, pre‑clinical and clinical testing, regulatory decision, like FDA approval, product launch, and post‑market monitoring.

In this version of this flow chart, it's only at this stage, at the product launch, that scientific advances funded by institutes like the NIMH, for example, move outside the lab and reach the general public. But that's not always how it works in the real world. So, science and translational medicine do not always proceed in a sort of neat linear fashion. So much of my research actually has focused on better understanding the places where information and technologies move beyond the lab really in unexpected ways; so where this idealized pathway of translation is disrupted in some fashion and specifically where the public has access to either information, products or technologies in ways that the researchers doing this work and the funders funding this work really did not intend and maybe even had not foreseen. And let me give you some examples.

So basic science and clinical research results are traditionally published in academic journals, which are really geared towards other scientists, scientists writing to an audience of their peers, but because of the internet, the public now has much easier and much earlier access to the results of research.

So, information about science flows a bit more freely than it used to. And so, this has led to the rise of do‑it‑yourself medicine and citizen science, where lay individuals are reading about experimental treatments and therapies, and in some cases‑‑ in some cases where it's possible to do so, they are self‑administering treatments before those treatments have been properly vetted and approved. And in other cases, companies are taking the products and technologies of science, even those that are really just still in development, and they're marketing them directly to consumers for wellness purposes in ways that circumvent FDA authority.

So, essentially, they're not proceeding with medical device approval, but they're taking the same technologies, not making any medical claims, and making them available directly to consumers without the need for physician direction or physician prescription. And finally, in other cases, even once a product or therapy does obtain FDA approval and the product is out there in the world, has been launched, it can be co‑opted in ways not intended by scientists or original developers of the technology, such as in alternative medical uses of biotechnology.

So, my research, I would say over the last several years, has examined different kinds of do‑it‑yourself medicine, direct‑to‑consumer products, and alternative therapies and the ethical issues that they raise, but I really spent most of my time thinking about these developments in the context of neurotechnology and mental health. So today I'm gonna be talking to you not just about do‑it‑yourself medicine and science as a whole, but specifically about do‑it‑yourself brain stimulation. And while I've done work in direct‑to‑consumer products writ large, today I'm gonna be talking specifically about direct‑to‑consumer neurotechnology. And while I've written about other kinds of alternative medicine and the ethics of alternative medicine, today I'm gonna be talking specifically about alternative neurotherapy.

Before I go forward, I just wanted to say a really quick word about why I think it's important to attend to uses beyond the lab, beyond this traditional pathway, especially as the work that NIMH funds and the work that mainstream or traditional investigators do is very much focused on this pathway. And that's because, as we saw with the COVID vaccine, just focusing on the development of the vaccine or any kind of therapeutic or any kind of treatment without attending to these larger social issues at play regarding public acceptance, public understanding of science, how the public interacts with these technologies, that can be detrimental, I think, in the end.

I think that means that we're missing a piece of the puzzle here, right? So even when we get to the stage of product launch, as we saw with the COVID vaccine, that doesn't mean that the public will accept it or in the future accept a given treatment or therapeutic. So, the public is getting information in all kinds of ways and interacting with different technologies and the healthcare system in certain ways, and I think it's really important for us to attend now, right, and not later to all the ways that the public might be utilizing devices and interacting with devices and techniques for mental health.

So, I'm gonna be covering these three areas today that you saw in that flow chart, the do‑it‑yourself brain stimulation, direct‑to‑consumer neurotechnology and alternative neurotherapies. My research has approached these phenomena from a sociological perspective. So, I use interviews, case studies and content analyses to better map and understand these phenomena, as well as the ethical and policy issues that they raise.

And so, my talk today, rather than diving into one specific study, I'm gonna stay fairly high‑level. So I'm gonna draw on some of the research that I've conducted, some of the research that my colleagues have conducted to give you a quick picture, first of what's actually happening in each of these areas, what these phenomena consist of, what they are, and then I'm gonna talk about some of the ethical issues that they raise and what initial steps, if any, have been taken to address some of these issues.

So, starting with do‑it‑yourself brain stimulation, what is this, what is this phenomenon, what is this movement? Well, it all started about 15 years ago when scientists began to experiment with this technique called transcranial direct current stimulation, or tDCS, and this is a basic schematic here of a tDCS device. You can see there's a stimulator which is basically inside there. It's just a battery, sometimes even a nine‑volt battery, with wires or leads, and at the end of each lead is an electrode; and when those electrodes are attached to the scalp and the stimulator's turned on, current is thought to flow through the brain.

So tDCS is an experimental technology, an experimental technique. It has not yet been FDA‑approved for any indication, and it differs from some more well‑known neuromodulation or brain stimulation techniques. So, for example, many people are familiar with DBS, deep brain stimulation, which is invasive, it's implanted. You know, it requires surgery to plant it deep in the brain. By contrast, tDCS is non‑invasive; so, it sits outside the skull. And tDCS is different from another more famous non‑invasive technique called ECT, electroconvulsive therapy, an approved treatment for treatment‑resistant depression. Obviously, DBS also is FDA‑approved, has been FDA‑approved for a while for neurodegenerative diseases. DBS and ECT are approved therapies, but ECT sends a very large amount ‑‑ provides a very large amount of current. So, it's effectively causing a seizure, where the amount of current provided in tDCS is very low. It may not even be enough to make a single neuron fire.

So tDCS has been researched for many years now, and I'll show you a graph in a minute of its popularity, but it really divides into two kinds of research. So, research on clinical populations to see if it has any effect for improving these clinical indications, as you can see here, but researchers also use it in healthy populations to see if it can have a cognitive enhancement effect, to see if it can improve things like motor skills, memory, creativity, problem‑solving, and a number of other cognitive functions. And so early research and I'd say ongoing research has indicated promise for both of these indications, both for clinical effects and for its use for cognitive enhancement in healthy populations.

I will say that research has been ‑‑ you know, a lot of these studies have been criticized for their small sample sizes. So, there is a debate about the efficacy of tDCS in the literature, but for the purposes of the home use of tDCS, it's a bit less relevant, but I think it's important to mention.

So tDCS really took off in the literature, if you look at this ‑‑ so this is a graph of the number of academic journal publications about tDCS by year, roughly in the last 20 years, and you can see it really started to take off around 2010, 2011. That's when the curve really ‑‑ 2012, that's when the curve really starts to go up. It is interesting to note the slight potential decline in the last few years from its peak in 2021. So, this is actually ‑‑ I should say this is from a title search of PubMed, a title search for either the term tDCS or transcranial direct current stimulation. So tDCS, this technique, this technology starts to take off around this time, and that also is exactly when we see the rise of do‑it‑yourself tDCS.

So essentially what's happening is that individuals are reading what scientists are writing about tDCS, seeing its potential effects for cognitive enhancement and for treating certain clinical indications, and because the device is relatively easy to make or build ‑‑ as I showed you before from that schematic, it's essentially just a device with two wires ‑‑ they're actually building the device at home. And so, we start to see people on YouTube posting about themselves using tDCS; there's a Reddit form that comes up dedicated just to the home use of tDCS and blogs and websites, all dedicated to this home use of do‑it‑yourself brain stimulation.

And so, in the early days of this movement, individuals created their own devices. So, they would share these circuit diagrams, share with each other which parts to buy. As you can see here, this is back when Radio Shack existed. They would tell each other which parts to buy, and people would go out and make these devices, and they would share the instructions on how to do this on these online forums. And the movement grew, and it evolved. If you didn't want to make your own device anymore, people began selling out of their home garages and basements devices and these device kits.

So, you can sort of buy an off‑the‑shelf device kit that just has the very basic batteries, wires and electrodes, and these range in price from about $40 to maybe $90. So, it is not hugely expensive to purchase one. And in the next wave, what we saw was people began to market these sort of slicker ‑‑ more well‑funded companies coming in and marketing these much slicker wearable tDCS devices. So, you can see these look a little bit different. You put them on; you don't have to have any knowledge of where to put the electrodes. You just put them on your head, and they connect right to your iPhone and deliver a little level of current to your brain. And these are early versions of the wearable tDCS devices.

The rise of this movement really caused a lot of controversy, particularly amongst scientists who were not too pleased about individuals using these devices at home. So, this is an editorial from Nature where several scientists wrote here, "Unorthodox technologies and applications must not be allowed to distort the long‑term validation of tDCS." And in the media, they issued many warnings over electrical brain stimulation.

So, researchers cautioned the public about the human risks of self‑administered brain stimulation, warnings over experimental brain foods, and there wasn't a huge amount of data on the safety. And I'll get to that in a minute, but, essentially, scientists were afraid of two things. One was that this home‑use community, these do‑it‑yourselfers would effectively ruin it. They were trying to see tDCS as this very scientific technique, trying to ‑‑ ultimately, the hope was that it would obtain FDA approval in some fashion. They didn't want these DIY‑ers to ruin it for the community. And with regard to safety in the laboratory, maybe occasionally it would cause a skin burn or some skin irritation, a very light burn, but they were warning individuals about these adverse events that could arise but also about the unknowns. There's a lot of unknowns about stimulating one's brain.

So, this was a media warning, and then we also saw international societies ‑‑ this was from the International Federation of Clinical Neurophysiology warning against the use of do‑it‑yourself devices and methods unless they have shown both efficacy and safety. So professional societies were taking official stances, issuing position papers against the home use of tDCS. And ethicists also really got into this conversation, and they issued a lot of calls to regulate these devices, you know, essentially that we need more regulation about these home‑use devices. And some people argued that existing regulations do not encompass these devices, these home‑use electrical stimulation devices, and that effectively we need to create new laws just to regulate these devices.

And so, this was ‑‑ I would say this conversation was happening maybe eight years ago, around then, and at the time, nobody had actually studied who these people were who were using them, what they were using it for, what sorts of devices they were using, what their practices were, where they were learning about how to use do‑it‑yourself tDCS. So, at the time, I did a number of studies from a sociological perspective that tried to answer those questions ‑‑ who these people are and what are we doing and how could that inform how we think about ethics, how we think about policies. And so, I conducted a number of studies. One was an interview study, another a digital ethnography where I spent a lot of time looking at the online forums, and I also did a survey of users of seven different consumer tDCS devices. So, I'll just share with you very quickly ‑‑ again, this is just a quick overview of my work, not in‑depth on any specific study. I'll share with you a bit about what I found.

So, the typical user was a wealthy, highly educated, politically liberal, 40‑something male, living in North America ‑‑ mostly the phenomenon within North America ‑‑ who reported being an early adopter of technology and frequently reading articles about science. Individuals reported using tDCS either for treatment ‑‑ the most common indications were depression and anxiety ‑‑ or for enhancement. Focus and concentration were the two main indications there. And I would say even these findings were very interesting, because early work ‑‑ or at least there was an assumption that these individuals were these 20‑year‑old males on Reddit trying to hack their brains, which was not untrue.

There was that population using these devices, but actually this larger study that I conducted found that a lot of people ‑‑ even though these devices are mostly marketed for focus and concentration and for enhancement, not for medical indications ‑‑ and I'll get into that in a moment ‑‑ my work found that actually a good portion of these people ‑‑ I think it was something like 40% of the individuals surveyed were actually using these devices for clinical indications, despite that not being their marketed use case, and there was an older population as well than people had expected.

Few individuals reported physical harm; so, we weren't seeing a lot of adverse events, but what I did find was that some individuals ‑‑ a very small user population stimulated more frequently and for a longer length of time than scientists did, which could potentially ‑‑ the effects of that were unknown, right? So, if scientists were stimulating for two 20‑minute sessions a week, these individuals were stimulating ‑‑ some had stimulated over a hundred sessions and were just going much longer and more frequently. Again, a small portion of users, but that raised some very specific safety concerns. And then finally, what I found was that users are using scientific papers to inform their stimulation practices. So, they were really turning to scientific research and looking at scientific papers to understand where to put the electrodes, how to use them. So really engaging with scientific literature.

And so, what are some of the ethical and regulatory implications of this work? What's the sociological study of these users? Well, I think first ‑‑ and this is what I argued in some of my work on these papers ‑‑ it's important to recognize that home users are utilizing tDCS both for treatment and enhancement. As I mentioned, this is not just these 20‑year‑olds on Reddit trying to hack their brains, but also there's a significant group of people using this who are frustrated with the lack of efficacy of existing treatments for their mental health conditions and they're turning to these devices at home and self‑treating themselves. I think it's important for scientists to be aware that this unintended second audience is utilizing published scientific research.

So scientists ‑‑ again, when you're publishing an article ‑‑ and as an ethicist, when I'm publishing an article in ethics journals, I have this imagined audience of people whose reading my work, but for scientists in this case, there was this whole other group of people who was really poring over their publications, and I think that merited extra care and attention to language. I argued that regulation ‑‑ or at least the regulation that was being proposed at the time would not be effective, as it would only encompass a small subset of devices. Many of these devices were making enhancement claims. Many were not even making any claims at all, and people were still using them and finding them. And I should say that to make new regulation may not be effective, not existing regulation.

As I mentioned, home users look to scientists for guidance. So, it's worthwhile to consider engaging with users. And this was a really interesting finding. So, these were people who have an affinity towards science. So, these were not your anti‑vaxxers, not your tinfoil hat alternative folks who don't trust science, don't trust the scientific enterprise. This was the opposite. These were people who were really into science but just frustrated at the pace that these therapies and treatments were trickling down to them. So, if they saw something happening in scientific literature, something they could do at home, they did it. They were very interested in doing it and administering it themselves.

So, I think the implication of that is very interesting, right, because it points to the fact that these individuals might be open to some engagement from scientists. And so, in part due to the work that I did, in part due to suggestions that others had made, there was this very interesting letter published in Annals of Neurology. It was authored by four neuroscientists and signed by several dozen others, and it was an open letter to users of tDCS, of transcranial direct current stimulation. And the letter took a very interesting approach, which I really liked. So rather than saying "Hey, users, stop doing this. What you're doing is stupid and you should just stop," this letter realized that that wouldn't work, because these individuals were actually quite smart and relatively well‑informed.

And so, this letter said, "Look, here's what we know about the effects of tDCS, here's what we don't know, and these are the things that you should consider when you're thinking about stimulating at home." So, it was more of this open engagement approach, which I think is actually the approach that's needed for something like do‑it‑yourself brain stimulation. My study of this had actually ‑‑ looking back, I wish I'd studied the impact of the letter. So, I can't speak to the sort of impact that it had, because my studies, as I'll show you in a moment, moved on to direct‑to‑consumer neurotechnology, but I think this was just a very interesting move and a very interesting approach. I should say also it's been several years since there was a lot of attention to this movement. It hasn't gone away, but it hasn't expanded. It's really remained a subculture that's still very much in existence.

Okay. So, moving on to the next ‑‑ so that's a little bit about brain stimulation, and moving on to the next topic I wanted to talk to you about today, which is direct‑to‑consumer neurotechnology. And I think you can see, based on my initial interest in do‑it‑yourself brain stimulation and how that movement went from home‑grown devices to devices marketed directly to consumers, it's very easy to see my interest in direct‑to‑consumer ‑‑ how my interest in direct‑to‑consumer neurotechnology came about.

But what is direct‑to‑consumer neurotechnology? This is how my colleague, Peter Reiner, and I defined it in a recent paper. So, it's the set of products, devices and software that are marketed to modulate or manipulate brain function that are sold directly to consumers. So, bypassing the physician, no physician prescription is needed, and they appeal to the fruits of the brain and cognitive sciences. And this piece is really key, because you could go into a new age store and find some crystals or special bracelets that might be marketed to improve your focus, but these products really are drawing from scientific advances, from the scientific literature, from advances in science.

And so, we talk about three different classes of technology that we see being in this realm of direct‑to‑consumer neurotechnology. Neurostimulation devices, which I've just told you about; neuro‑recording devices, so these are devices that use technology like electroencephalography, EEG, to record activity from the brain; and we also did include brain training software in our definition, because they do meet the definition that we set out for direct‑to‑consumer neurotechnology. So, I'll just go through really briefly each of these categories, really focusing more attention on the EEG and just talk about some of the ethical issues that these devices raise. I've already told you about the history ‑‑ the emergence of direct‑to‑consumer brain stimulation devices, but I'll just say they're still on the market. I'll talk about the regulation of them in a minute, but we have this sort of next generation of these devices today and you can see some of the ways that they're marketed. This is the Fielding energy patch, marketed for energy and focus, and this is a device that apparently appeared on Shark Tank somewhat recently for improving focus, attention, memory, and productivity.

So, I've already talked about the stimulation devices; so, I'll probably spend most of most time here just on the recording devices. Many of these devices use EEG, electroencephalography, which is a very old technology, about a hundred years old. It's used widely in brain science research. It's also part of standard medical care, used to monitor sleep and also used in epilepsy. But in the early 2000s we saw the first consumer EEG devices come to market. They only had one or two electrodes, compared to the many more electrodes you saw in the earlier diagram, and it was really unclear if they were actually reliably measuring brain signals. And we had early applications of consumer EEG devices that focused on object control. So, you could, in theory, use the device to wiggle cat ears, do basic control of a video game, control a toy helicopter, but these never really took hold in the mainstream. They really remained novelty items, probably because the signal wasn't all that reliable.

So, in the mid‑2010s we see a shift and consumer EEG devices begin to be marketed for wellness. As you can see here, this company is marketing their headset for mental fitness. Others marketed their device or are still marketing their devices for relaxation and focus, and the marketing images indicated that these devices could be used equally both for older adults and for children. This is all despite the fact, as I'll get to in a moment, that there's actually been little evidence that these devices actually do improve wellness. And so today we have the next generation of EEG devices that are being developed for applications such as control, wellness and focus, and you can see these have a bit of a sleeker look.

It's worth noting that other kinds of brain recording devices using technology other than EEG are being developed. This one here is the Cardinal Flow. It's being developed ‑‑ it's actually being used in research settings now, but the company has stated that it wants the device to be used for consumers. It uses a technology called EFNEER, which at the moment involves a big helmet and it's actually tethered; so, there's wire at the end. We have Meta, who are developing a wrist‑worn wearable that uses EMG, electromyography, to measure signals from motor neurons to enable different kinds of control. Just by using finger movements, it'll pick up on your intended ‑‑ or your actual finger movements that you'll be making. And we have companies like Apple, who hasn't been very public about what their plans are for neurotechnology, but they did file a patent back in July that indicated that they might be trying to incorporate EEG into their Air pods.

And of course, the man who has brought the idea of direct‑to‑consumer neurotechnology to the general public, we have Elon Musk, who cofounded a brain‑computer interface company called Neuralink. And Neuralink is starting out by working on medical applications of its brain‑computer interface product, but Elon Musk has been very clear that he wants to see the Neuralink product be used in the wider population, after it goes ‑‑ starting with medical and then moving to the wider population.

So those are different kinds of recording devices that have been on the market, and sort of looking to the future, may be on the market in the future. And I'm not gonna spend much time on apps for mental health and brain training, other than to say that there's been a massive, massive proliferation of these apps that really bypass the physician. Some are marketed for wellness purposes, some are marketed for medical indications, probably illegally, and there's many, many brain training apps out there. The market is flooded with hundreds, probably thousands of these applications.

So, what are some of the ethical issues related to direct‑to‑consumer neurotechnology? Well, in the U.S. consumer neurotechnology falls into a gray zone. So, in short, the FDA exercises enforcement discretion. So basically, it looks the other way for all low‑risk devices marketed for general wellness. FTC could potentially take action and they have taken action against several companies in the brain training software space, most notably Lumosity several years back. And the Consumer Product Safety Commission can take action to prevent consumers from unreasonable risk of injury from a consumer product, but they have not taken action either. So, it's a bit of a gray zone here, and at the moment, neither the FDA, FTC or Consumer Product Safety Commission has actually taken ‑‑ at least publicly, has taken regulatory action against any of the neurostimulation or neuro‑recording devices. Another major ethical issue that I've written about quite a bit is misleading claims in this space. So, companies' claims have largely outpaced science. So, my colleague, Robert Thiebald, and I wrote a paper a few years ago called "Mind‑Reading or Misleading," where we looked at claims made by consumer EEG companies and found that the scientific evidence to support their claims of wellness was fake.

And then we have an issue that's garnered a lot of attention, I'd say in the last year or two, which is related to privacy of brain data collected from consumer devices. So, one view on this topic ‑‑ and there's different views ‑‑ is this one. With advances in neural engineering, brain imaging, and pervasive neurotechnology, the mind might no longer be such an unassailable portrait. So, this view, which is also represented in my colleague Nita Farahany's book, "The Battle for Your Brain," is that these technologies, these consumer neurotechnologies ‑‑ and again, I spent a bit of extra time on the recording technologies ‑‑ may reveal very personal information about the brain. And because these devices may not be considered medical devices, that information might not be protected by HIPAA, and therefore, we might need another source of laws or legislation to protect our brain privacy or our mental privacy.

And there's been a lot of move towards ‑‑ a lot of activity really even just in recent months. This is an article from the New York Times back in April, reporting on the Colorado law that extends privacy rights to neural data collected by technology companies. A similar law just passed in California, and this was really on the heels of advocacy efforts led by the Neural Rights Foundation, cofounded by neuroscientist Rafael Yuste at Columbia University, who also ‑‑ Rafael and the foundation actually got an amendment passed in Chile just to protect the privacy of brain data. But I should say that there's some debate within the world of neuro‑ethics, those of us who study ethical issues in neuroscience, about whether this is the right approach, about whether new rights are needed to protect brain data.

And so, in my view and in the views of some of my neuro‑ethicist colleagues, we see protection of neural data as part of a larger data privacy challenge. Personally, it's not that I'm not concerned about data being collected from these devices, but that I'm much more concerned about all the data that's being collected about me now, from my email, from my browser history, from my Apple watch, from my phone. Taken together, all of that can reveal very, very personal information about me, and I'm not sure that EEG will ever ‑‑ data collected from EEG will ever be as revealing as all the information that's being collected about me. So, again, not that I'm unconcerned; it's just that I'm more concerned at the moment about what can be revealed and the lack of protections, I should say, for all this other kind of data. So those are not all the ethical issues with direct‑to‑consumer neurotechnology, but just some of the ones that have ‑‑ again, this is sort of a high‑level overview talk, just some of the ones that have gotten more attention recently.

Now, coming to the last phenomena that I wanted to cover, alternative neurotherapies. So, I just thought I'd share with you very quickly how I became interested in alternative therapies. This area has gotten, I would say, less attention, but I think it's actually probably one of the most important areas. So, when I was studying home users of tDCS, transcranial direct current stimulation, what I found so fascinating was how you could have multiple uses and users of the same technology, people interpreting and using the same exact technology in different ways.

So, you have researchers using tDCS in the laboratory, applying tDCS to subjects for the primary purpose of research, and they exist in this very controlled and regulated environment. So, every time a researcher wants to do a study, they have to submit a very detailed protocol in advance to the IRB; there's institutional oversight, but you have at‑home users using tDCS at home and sometimes they actually use the same exact technology applying tDCS to themselves. The primary purpose, whether they're using it for enhancement or for treatment, they're trying to improve themselves in some way, and they're in their basements or their bedrooms. So, it's a very uncontrolled environment.

So, I was really fascinated by this, by these sorts of different uses. And then sort of as time went on, there was a third party that was in the mix that drew my attention, that I found completely fascinating, and this was alternative medicine providers. So, they're actually using tDCS in the clinic. Again, this is not an approved treatment, but they're still using it in the clinic, applying tDCS to patients or clients. The primary purpose is clinical treatment. Actually, as I'll show you in a moment, they're using it both for treatment and enhancement, but they're treating patients, and they exist in a semi‑controlled environment. So, there's some state regulations, but they’re not as strict. They're not typically in institutional settings, there's not this strict kind of oversight. And so, this sparked my interest. I began to see people using this in the clinic and this sparked my interest in looking at how these alternative medicine providers were using all kinds of neuroscience therapies and devices. So, I just wanted to share with you just a few of them.

So, what are alternative neurotherapies? What are we calling alternative therapies? And this is taken from a paper that my lab wrote a few years ago. So, some of the key characteristics. The use is not considered to be standard of care by mainstream medicine. Treatment is not typically reimbursed via health insurance. The scientific evidence supporting use is not typically robust, rigorous, or conflict‑free. The provider training typically varies quite a bit, and they're often self‑described by the providers as an alternative to mainstream medicine. This is how the providers describe them. And we consider a number of different technologies to be within this realm of alternative therapies, and I'm gonna share with you a few of them.

So, the first is SPECT diagnostics. So, in traditional healthcare settings, SPECT imaging is used to evaluate neurological disease, but there are over a dozen clinics in the U.S. Some of you may have heard about them, Thaymen Clinics offering SPECT scans for neuropsychiatric diagnostic and evaluation purposes, even though it's not recommended for any of these purposes, but we have clinics out there marketing the sort of diagnostics that's not supported by mainstream medicine. We have brain stimulation techniques. I mentioned that many different clinics had individuals administering tDCS to different users. Here's just some screenshots of some of them. In addition, there's also other alternative uses of brain stimulation techniques.

So TMS, transcranial magnetic stimulation, is FDA‑approved for a number of indications, a number of mental health disorders, but there are individuals marketing it for all kinds of off‑label indications. This is one screenshot from a provider's website. So, you can see, "Not only can we treat depression, migraines and OCD, but we also treat autism, Asperger's, TBI, bipolar, mild cerebral palsy." These are not indications that are supported by a good amount of evidence.

And so, we actually did a study in my lab where we actually looked at the off‑label indications that providers were marketing TMS for. This is the off‑label indications from about a hundred different clinics, and we found that while some of the off‑label indications did have supporting evidence ‑‑ and I believe that actually some of these may have garnered FDA approval since we did the study, but some of the indications did have evidence supporting their use, but some of them, such as the use of TMS for autism or MCI, had less evidence supporting their use. So, brain stimulation is another area that we see alternative neurotherapies.

And finally, the last one, which I've really been endlessly fascinated by, is neurofeedback. The idea with neurofeedback is that if you have access to your brainwave activity, if you could see the real‑time output of your brainwave activity that's being recorded through EEG, maybe you can detect some abnormal rhythms and maybe you could then modulate or adjust your rhythms in real‑time and then improve some aspect of your behavior. It's a very ‑‑ it's really widely provided, but it's very controversial. So, it's marketed for the treatment of both clinical indications and non‑clinical indications, and I'll show you what I mean by that in a moment. There's probably about ‑‑ I think we calculated this based on membership in professional societies, but there's over 15,000 providers offering neurofeedback globally, and there haven’t been that many great studies of neurofeedback.

The best studies that have been done are in the realm of EEG neurofeedback for ADHD, and the results have indicated that it's not any better than a placebo. It is a controversial technique that's not recommended by any physician or society. This is sort of what the marketing applications ‑‑ this is what some of the websites of these providers look like: "Train your brain to heal itself; pain‑free natural alternative to medications and other therapies; think of it as exercise for your brain; taste the freedom of a thriving mind."

I see I'm getting closer to time here, so I'm just gonna run through these last bits. So, what are some of the ethical issues in this space? Truthful representation of evidence‑based; again, we saw that with direct‑to‑consumer neurotechnology. We did a study looking at all the claims, all the advertising claims made by neurofeedback providers on several hundred different websites. We found anxiety, ADD, depression. They're marketing neurofeedback for all these indications and there's really not robust evidence supporting their claims. They are also marketing neurofeedback for enhancement, and we found that almost all websites advertise neurofeedback for at least one non‑clinical indication; non‑clinical indication being mostly cognitive enhancement, mood and wellness, or even improve your general performance or athleticism. So misleading claims are a major issue in this space.

Provider competency and scope of practice, another major issue both in the neurofeedback space and in the off‑label TMS space. So, in the neurofeedback space, we found that very few providers had the training, had the relevant degrees or training. Very few had psychology degrees or M.D.s, and many of them have these short certificate courses, as you can see here, in neurofeedback, but they don't really provide much training in dealing with the clinical indications. With off‑label TMS, it's actually usually M.D.s who are administering the TMS, but there was one M.D. who was on the website that I just showed you who's trained as a pediatric oncologist but is administering off‑label TMS for things like PTSD. So, scope of practice, I would say, and competency is certainly a concern in this space.

Other potential harms ‑‑ the risk of physical harm is relatively low from all the different therapies I just mentioned. They're not completely absent, but relatively low. Considerable out‑of‑pocket financial costs for these treatments. These are not typically covered by insurance, and as ethicists we talk about something called opportunity cost, which is the cost of choosing a non‑empirically supported treatment instead of a validated one. And I should say that many of the technologies of these alternative neurotherapies are marketed to individuals who are fairly vulnerable, and a good proportion of them, as we saw in the studies that we did, are actually being marketed to parents to treat their kids with ADD or autism.

Okay. Getting closer to time, so I want to wrap up, but this is sort of ‑‑ I've taken you on a journey through three different ways, three different social phenomena related to this idea of moving beyond the lab. And so do‑it‑yourself brain stimulation, another way of conceiving this or conceptualizing this is, I think of it as primarily an issue related to information.

So, each of these phenomena raises slightly different ethical issues, require slightly different regulatory or policy approaches. So, it's very hard to regulate information, right? So, I think the approach here, as I mentioned earlier, is really related to better engagement with users. With direct‑to‑consumer neurotechnology, when we think about policy or we think about regulation, this is really related to the sale of products. So, this is where regulation ‑‑ depending on what it's regulating, but this is where it potentially could be effective. These services, the alternative neurotherapies are much trickier to regulate. Regulation would have to come at a state level, but probably also engaging with these communities would be beneficial.

So, I wanted to bring you back, just to close with this diagram that I started with. So this talk today was about specific instances of all these different phenomena in the realm of neurotechnology, but I just wanted to say that these phenomena are ‑‑ they're not just neurotechnology, not just brain stimulation, do‑it‑yourself brain stimulation, but these phenomena are ‑‑ we're seeing do‑it‑yourself medicine and science in other areas, like thecal transplants, hormone replacement therapy, do‑it‑yourself diabetes. With direct‑to‑consumer products, it's not just neurotechnology that we're seeing, but we're seeing all sorts of different prescription products and laboratory tests offered directly to consumers.

So, the same with alternative medical uses. These alternative medical uses really thrive in areas where there's non‑invasive medical devices, because there's less restrictions on who can prescribe. There's much stricter restrictions about prescribing pharmaceuticals; there's virtually no analogous restrictions on using medical devices in a clinical setting. So, this is just all to say that we delved into very specific examples in the realm of neurotechnology, but these are phenomena that we see in other areas. These are specific instances that I talked about today of a much larger social phenomenon.

And so just to conclude, I think there's really been this fundamental shift in the way that the public is accessing and using medical and scientific information and products, especially in the realm of neurotechnology. Funders, researchers, clinicians, policymakers, and professional medical societies, I think, should have a much greater awareness of these developing social phenomena. And I think these phenomena have traditionally been dismissed as not worthy of scholarly attention, things we don't need to study because they're outside the pathway. I personally think that's the wrong approach. I think we really need to better attend to how the public is interacting with these technologies and devices beyond the lab.

And with that, I will conclude. Okay, and I wanted to thank NIH for funding. So, with that, I'm happy to take any questions. And thank you very much.

SHELLI AVENEVOLI: Thank you so much, Anna. That was a really great talk, very interesting and provoking. I see you've been answering some questions in the chat. So let me ask you if there are any of them you might want to answer out loud that you thought might have general appeal. Otherwise, we can go to a couple more that are in the chat, although you're typing answers and speaking too.

ANNA WEXLER: Yeah, this is actually kind of ‑‑ this is the first time I've done a recorded talk and I've been able to respond in the chat. So, it was pretty fun. I will just say there were several questions about demographic information with regard to tDCS, and so I put the link to the papers in there. Because I was trying to cover a number of different topics in this talk, I wasn't able to dive in‑depth into any one study or especially any of the methods in these studies. So, I would just encourage you ‑‑ if you're interested in diving further, the research is there and some of the links to the papers are in the chat.

SHELLI AVENEVOLI: Great, thanks.

I'm noting a question that just came in about whether there are side effects of the do‑it‑yourself neurotechnology use.

ANNA WEXLER: Yeah. So, there are side effects, and there were a few questions about that. So, I just responded to a different one in the chat about side effects of neurotechnology. So, in short, there were side effects. I think we would probably characterize them as minor. I mean, there were things like headache, tingling. One of the things that I remembered we had some difficulty characterizing, because this was an open‑ended question, was when people reported something like burning. Is it a burning sensation? Do you actually have a severe skin burn? Is it just redness that you're interpreting as burning? Obviously if it's burning, it's concerning, but we had a hard time ‑‑ it was very interesting just from a data collection perspective trying to understand the severity.

So, we did, I believe, code ‑‑ when participants mentioned a very serious burn, we did code those, but that was maybe only a handful of cases. I mean, overall, this was not a technology that's sending people ‑‑ that's causing very serious adverse events. That's not to be dismissive of the lesser potential side effects that were there, but when you're thinking about it in contrast to things like supplements that people are taking and are ending up ‑‑ that are sort of marketed widely and that they are ending up in the emergency room, there's a lot of data on this. This is not technology that rises to that level of risk, in my opinion.

SHELLI AVENEVOLI: Thank you. Noting only two minutes left, I was just curious about your perspective of ‑‑ basically the thesis running through is that we should be mindful of what we're doing as it's interpreted and used by the public. What could NIMH be doing differently to address that?

ANNA WEXLER: I think one is attending to this. So, I know there is ethics funding from NIMH, but making that more explicit to investigators to sort of encourage them to think about the downstream implications of their work, especially since we have seen a lot of unexpected and unintended uses especially in the area of mental health. So, encouraging investigators to consider things, potentially even explicitly, in their applications, and I know that ethics components are now required for a subset of grant applications.

So, one could think about requiring them for additional applications, right? Even just having investigators start to anticipate and think, "What could be happening with this technology that I'm developing down the line?" Because it's often hard to think about those things. I mean, I know. I write grants. You are focused on getting your grant out, and science has to be good, and the methods have to be strong. So, you're often not thinking or anticipating what's going to happen down the line, but any mechanism to get people to spark awareness of that and spark thinking, I think, would be tremendously beneficial.

SHELLI AVENEVOLI: Fantastic. So, I think we should end here, just because of time. And thank you again for sharing your perspective and your time with us today, and we really appreciate it.

ANNA WEXLER: Thank you. Thank you for having me.

SHELLI AVENEVOLI: Thanks, everyone, for joining. See you at the next one.