Exploring Frontiers in Neuroprosthetics and Ethics: An Interview with Dr. Xing Chen

Thanks for joining us, Dr. Chen! I want to start by saying it is an honor to talk to you today. Your inspiring career has taken you from Newcastle University via the Netherlands Institute for Neuroscience and Phosphoenix to a tenure-track position at the University of Pittsburgh School of Medicine. What has motivated you to pursue a career in bionic vision?

Xing Chen [XC]: I had initially pursued a biology major during my undergraduate years at the University of Southern California, with the intention of building on my high school interest in the subject. I had the chance to read John Ratey's book, "A User's Guide to the Brain," which explored various neurological disorders, like Capgras Syndrome. I found neuroscience fascinating and thought it was probably a subject in which I could be interested for many years. This fascination helped guide my decision to switch majors to neuroscience. I became inspired by captivating neuroscience courses and research articles, especially ones focused on electrophysiology recordings in monkeys engaged in complex cognitive tasks. I was just amazed that the researchers were able to record from individual cells in the brain and correlate the activity of the neurons with behavior, all while aiming to understand what happens mechanistically when the monkeys were moving their eyes or doing different tasks. That passion is how I ended up going to Newcastle University for my PhD, and I just fell in love with monkey work.

After Newcastle, I found my next position in the Netherlands where my supervisor wanted to record from 1000 channels. I really wanted to expand on the work I did in my PhD, which was recording from dozens of electrodes in the brain. At that moment in my career, I knew this project was exactly what I wanted to do. I wanted to apply all my skills, work with monkeys, conduct analyses, and take the technology one step further by having more channels while having the potential for a translational application.

I've just gone from one dream project to the next across my career, and now landed in Pittsburgh. Again, this is another dream job where I'm able to just be independent, come up with research projects and lead a team. I've been very, very lucky, with a combination of timing, interest, good luck, and hard work.

How has your previous work and research experience impacted where you are today and your current position at Pittsburgh?

[XC] I found out pretty late (around my junior year of undergrad) that I needed to gain some research experience. I started working in a molecular biology lab, which gave me my first taste of research, as well as an Intro to Programming class in my last semester. It was a lot of “just in time” realizations of what I needed to do in order to move into research. During my PhD, working with animals gave me the foundation for running complex behavioral tasks, analysis of neural data, looking at multi-human activity, and doing experimental work and data analyses. Going from recording to stimulation in my postdoc, I became familiar with how to deliver currents using different stimulation parameters, how to remove stimulation artifacts from the signals, how to train the monkeys behaviorally, and to have them report that they saw the phosphenes in the first place.

I did my postdoc for close to eight years. I went from doing a lot of the lab work to being involved in larger collaborations with groups of labs across Europe, mostly in the Netherlands, but also in Spain and Germany. We had people working on the electrophysiology side of things, but also working on probe development, the creation of novel devices, and clinical work. We also had collaborators working on the AI aspects and the conversion of images into instructions for brain stimulation. There, I started to learn more about the regulatory process of how to get a device approved firstly, for in-human trials, and then eventually for CE/FDA approval.

That put all these processes and different disciplines onto one map, and that's how I also learned to work more collaboratively with people and set up interesting experiments where you really rely on the skills of others. Firstly, having that understanding of how to run the experiments is critical - how to set up new collaborations and come up with new ideas, how to lead people, how to manage people, and how to communicate effectively. Making sure that you keep tabs on what people are doing, how they feel, how they want their career to progress, and how to motivate others are equally important abilities. Those are really important management skills that I picked up gradually from mentoring students, to supervising Masters and PhD students, and taking management courses along the way.

In terms of your work regarding expanding the number of electrodes in an implant, it seems like more isn't always better. How does this relate to your recent finding that it is unknown whether devices with high channel counts will be suitable for human implantation?

[XC] I think that's one of the huge issues in this field, and to be honest, one that hasn't been talked about too much. There have been quite a few really good studies in the past which examined the spread of current across tissue and tried to estimate the amount of interaction between currents from adjacent electrodes. There's also been quite a bit of work done with surface electrodes via the Orion study, but current thresholds for surface electrodes are several milliamperes, and they observed a serious adverse event (a seizure) in one subject and hence avoided delivering stimulation on multiple electrodes simultaneously. Similarly, when moving to intra-cortical electrodes or smaller penetrating electrodes, I think this risk is still not very well studied.

I think there's still a lot that's unknown about how many electrodes we can safely stimulate simultaneously. One of the experiments I'm planning to do is going to actually try and shed light on this question. I want to carry out simultaneous recording and stimulation to better understand how to avoid evoking abnormal activity. In my opinion, that's a potential risk for patients and a critical question to address.

Another question is related to the number of electrodes that should be stimulated in order to obtain functional phosphene vision, and if it's possible to achieve functional vision with smaller numbers of electrodes. So maybe the point about epilepsy attacks is moot and it's not even a real concern, but the problem is that we don't really know the answer to that yet. Regardless, it's going to be a process of experimentation.

Over your years of working within the neuroscience and neuroprosthesis fields, what major changes have you seen in scientists' approach to restoring vision and how has this influenced your own approach?

[XC] I think that one of the most interesting changes has been the fact that people have received approval to do experiments in humans, leading to so many new insights.

I think some of the most interesting technological developments are the use of wireless technology such as in ICVP, and the use of flexible materials, like we're seeing with Neuralink. It still remains to be seen how these implants will do in the long run in people - but right now, in my opinion, these are some of the most promising developments to date. As a field, we really hope that this will lead to extended longevity and biocompatibility of the implants.

I also think that there’s a lot of discussion about ethics, which is really, really crucial, and of course, these discussions are not new. I read a book which came out in 1971 on visual prostheses, which is a compilation of conference proceedings on work that was done in the 60’s. They talked about a lot of issues which are still so relevant today, for example: Who should volunteer for implantation during the experimental stages; who will stand to benefit sufficiently from this technology; exactly what level of spatial resolution is required; what will the technology be used for; will this yield improvements over alternatives such as sensory substitution devices? More recent discussions in recent years have focused on: What happens if you have an implanted technology and the company that produces the device fails? What happens to patients? I think there's a lot of increased scrutiny and awareness in the media and amongst the public, especially after what happened to Second Sight’s patients. With the Argus II and Orion as well as Retina Implant AG’s Alpha AMS, and some other companies, several patients have shared their experiences and been very vocal about what went well or badly, which yields priceless insights in terms of ethics. I feel like there's now a greater understanding of the limitations of existing technology, the significant risks involved, and even some understanding about the finances involved in a clinical trial.

All of this, I feel, has really percolated into the awareness of the general public, and there are actually broader societal discussions around that. It's really necessary to calibrate the public's expectations as to what is achievable with these devices - what are the risks involved, who’s going to pay for them, and what's going to happen to patients? I think these are very positive developments, even though patients have been left without a lot of resources in some cases. I think those past situations have helped us be more aware of the potential pitfalls today.

I also believe that getting to know people who have been implanted with these devices has been one of the most transformative aspects of this job. Knowing people who are willing to take those risks, who have experienced the roller coaster of enrollment in these studies, who have regained some perception, and/or had their devices stop working or stop being supported, is extremely inspiring and motivating. Talking to them, knowing them, and eventually seeing some of them as friends has really helped to put my research in perspective and actively prioritize the wellbeing of real people. I believe that's one of the reasons why I think we should have as many interactions as possible with end users.