• JoJo

Marom Bikson Is Making An Impact

Updated: Oct 11, 2019

In the world of neurotech research, Case Western Reserve University serves as our inherent “Six Degrees of Kevin Bacon.” In fact, at the 2018 NIC Conference in Minneapolis our happy hour gathering became an impromptu CWRU reunion. How can it be avoided? With the Neurotree lineage of Thomas Mortimer, Dominique Durand, Warren Grill, Hunter Peckham, Cameron McIntyre, Dustin Tyler, Bob Kirsch – and the list of names too long to enumerate, you’ve peopled half of the neurotech continent. In this list of giants in implanted neurotechnology, how does CWRU turn out a non-invasive expert like Marom Bikson? Well my Dears, I’m glad you asked because it’s quite a lovely tale. So, grab a chair and let me pull on your ear for a bit.

“After stepping away and not having direct collaborations for almost two decades, now I’m talking to these [CWRU] friends and now they’re becoming colleagues again,” said Bikson when I asked him if he had any collaborations with his classmates or professors at CWRU. The dearth of professional cooperation seemed odd to me given the kinship that I generally associate with the Case alumni. The source of the departure and the reconnection is better understood when we look at Bikson’s chosen area of research which has largely focused on tDCS and, most recently, brain signal transplantation.

“There was not much work at CWRU in non-invasive stimulation. By picking that area for my research I had to leverage a lot of the tools that were developed at Case, but I also had to adapt them and create a new sort of toolkit of neural engineering for non-invasive electrical stimulation,” Bikson said. “I’m starting to work more and more with them,” he continued. “For example, I’m working with Rafael [Carbunaru], who was a student of Dominique’s and now he’s directing R&D at Boston Scientific. And the reason these things came full circle is because all of a sudden, the fields of invasive and non-invasive neuromodulation that were seemingly different started to push in against each other. All of a sudden, high frequency became relevant for non-invasive and all of a sudden, subthreshold became relevant for invasive. And oscillations became relevant for everything. Closed loop became relevant for everything. And in this way, I’m starting to work more in spinal cord stimulation, but I’m doing it with toolkits that we developed for non-invasive neuromodulation. Another example is individualized modeling was pioneered first for invasive but was pushed ahead for non-invasive. A lot of those tools can now be applied back to invasive.”

One of the most notable conferences in our industry is North American Neuromodulation Society (NANS) whose attendees are largely in the clinical space and its content focuses heavily on invasive neurotech, SCS and DBS in particular. When Bikson agreed to partner with Elliot Krames, past president of the International Neuromodulation Society (NANS’s parent organization) and Eric Grigsby to join the Neuromodulation: The Science conference with Bikson’s own New York City Neuromodulation conference I was unsure what the result would be. The answer: an undeniable success.

“NTS shares a lot of deep DNA with NYC Neuromodulation; it’s a conference that ties the science to the clinic and the notion that they must stand together,” Bikson told me. “A lot of basic science in the absence of translation, well you could just as well be walking in the woods, it’s not going to be clinically impactful. At the same time, the best clinical trials and the best clinical practices are informed by basic science. The value of this two-way interaction seems obvious, but are there really meetings where the clinicians really speak to the scientists? I think that with NYC Neuromodulation and NTS we tried to create an environment where that will be very effective.”

I attend many conferences every year and honestly, they’re not all great (you know I’m right.) They’re a little like visiting relatives for the holidays; you have favorite family members, others are worth a few minutes of chit-chat around the Kringle, and then there are the ones that you tolerate only because you have to. Although I had not previously attended NYC Neuromodulation, I have had the privilege of seeing the evolution of NTS since its first gathering in Orlando in 2014. The complement that Bikson’s influence supplied was a key ingredient in the range and depth of content in this year’s program. The program included a plethora of talks on BMI, SCS, DBS, NIBS, modeling, closed loop neuromodulation, bioelectronic medicine, and more. “The idea is simply that when you talk about the science of brain stimulation, you need to move across all of these domains and not stay in silos,” Bikson told me.

Cynthia Chestek, Cristin Welle, Sarah Laszlo & Marom Bikson at NTS/NYC Neuromodulation 2019

I spoke with Bikson about the fact that NTS/NYC Neuromodulation had the very first all-female session that I had ever seen. “One of our sessions is neural engineering and it has a heavy focus on hardware, particularly for BMI and brain recording. We looked wide and hard for the most innovative speakers, not just the usual suspects,” explained Bikson. “For this panel we recruited engineers doing great work and they all happened to be women.” And Bad Ass women at that: Sarah Laszlo, Cristin Welle, Cynthia Chestek, and Maryam Shanechi. (Shanechi was unable to attend at the last minute and her talk was supplied by proxy.)

“I think in general, the conferences that I’ve been involved with have always been diverse. I think that if your approach is to say, ‘who did I see at the last conference and who were the keynotes?’ that you’re going to get one set of speakers,” he said. “But if you follow the literature closely and you’re looking to see who the rising stars are and you’re looking to see who’s a good speaker and a good communicator, you may get a different set of speakers. I like to think that the second set are the ones that we’re recruiting for our conferences.”

In the past ten years or so that I’ve been lurking around the neurotech field I have seen discernible changes. Maybe I wasn’t looking in the right places in my early days, but I’ve noticed an expanding variety of disciplines joining the field of neurotech. It feels like the field is not just engineers and neuroscientists with an occasional biologist anymore. I receive a number of inquiries each week from students at varying places in their education asking how they can get into neurotech. Many feel as though they don’t have a chance because they’re not engineers. I asked Bikson if he saw a trend in students at his institution or the field in general.

“All of my degrees are in biomedical engineering and I’m faculty in biomedical engineering. Biomedical engineers have a particular skill set that is well suited for a variety of problems,” said Bikson. “But I think the field of neurotechnology at large is really welcoming to a variety of skill sets. We need cognitive neuroscientists, we need psychologists, and physicists in order to thrive. All of these are great educations to work in neurotechnology. If you’re a biology major, you’re going to have to pick up some physics. If you’re a physicist, you’re going to have to pick up some machine learning. Often what will happen is that people will ground themselves in what they’re comfortable with, but you pick up a different discipline to supplement that comfort zone. If your background is psychology and you come into my lab you have a great set of skills to assess the effects of stimulation on cognitive performance – but you’re going to have to learn a little bit about Ohm’s law, and electricity, and electrodes. There’s no reason to be intimidated. This is a welcoming field and everyone has a role to play.”

Bikson’s own lab is a reflection of his belief that there is no single correct path into neurotech. Within his lab you will find people that contribute to the full spectrum of device development including computational modeling, animal models, preclinical testing, device design, electrical and mechanical engineers, human trials specialists, and more. Bikson maintains dozens of collaborations, including the budding projects with Case Alumni, where his lab members will serve as engineering liaisons – forcing each person to develop strengths in a particular domain while also integrating complementary skills from other domains. I asked him to provide some examples of how that works. “You might be doing a lot of computational modeling work and you’re also supporting the initial prototyping of the device. Or, you might focus on prototyping an electrode design but you’re working hand-in-hand with the people who are doing the clinical trials.”

The trend toward requiring a multifaceted workforce within neurotech has certainly been growing. I know that in the recruiting that I have done in the field, more and more clients will be hiring for a neurophysiology position, but will test candidates on general knowledge in other areas such as materials, modeling, or basic engineering. It can be difficult for the hiring entity and daunting for the candidate when so much knowledge is needed. Shifts in training are starting to happen and students are exposed to this transdisciplinary approach earlier and earlier in their programs. In Bikson’s lab, students maintain different areas of specialty who can match across disciplines to get a complete picture of the device process.

While each of Bikson’s students may have a different focus area, he or she is also likely to have varying career goals. I sometimes assume that teaching at this level is not too different from parenting. Each student has their own competencies and designs for the future. To me, that means that each student will need different mentoring; I’m glad that Bikson agreed.

“Making sure that my students are prepared for what they want to do is critical,” said Bikson. “For example, if they’re interested in an academic career, my job as a mentor is to lay the groundwork for them to be successful – really publishing papers, hypothesis development, focusing on writing skills, and getting them on sound footing to launch in that direction. On the other hand,” he continued “if I have a student that wants to go into industry, the publication base doesn’t hurt, but it’s really not make-or-break, it’s more about the skillsets and have they developed the right skillsets to move into industry?

“Like all labs, we produce scientific insights, we produce products, and we produce students. With students, which make up three quarters of my lab, they’re not here to stay. They have somewhere else they want to go,” he told me. “I would say that my lab produces people with unique skill sets. I think the way that we approach things is slightly different. My students tend to have a slightly different skillset and so they tend to solve problems in innovative ways that is valuable in both academia and industry.” Regardless of where you go after Bikson’s program, in order to land a position in his lab he expects people to be hardworking, willing to speak their minds and to defend their opinions, but also to listen. “People who have their heart in the right place tend to be good scientists.”

Not ever having been a scientist myself, I imagine that there are moments when an experiment just doesn’t work. Honestly, none of my experiments ever worked; Mr. Simms will attest to that and I’m quite certain that I directly contributed to Mr. Fogwell’s early retirement. I often wonder what the more soul-crushing experiments have been in a scientist’s past. I’ll save you a little angst here, I know it’s a nail-biter, but one of Bikson’s most er, uh, challenging experiments lead to one of the papers that has brought him the most pride. It all harkens back to his postdoc days at the University of Birmingham.

“The study characterized the effects of direct current electrical stimulation on cellular function using a brain slice preparation and asked basic questions about what happened when you apply direct current stimulation to a pocket of cells. Do they become more excitable? Less excitable?” he patiently explained to me. “That work took me a couple of years to really figure out the rules and initially it was really complicated. I would do an experiment one day and I would see things go one way. I would do the same exact experiment the next day and things would go the opposite way, and then back the next day. I kept stimulating this clump of brain in the same way and I would see a different response and for two years I was coming in six days a week and I couldn’t resolve it.

“I was this close to publishing a paper that said, ‘When you apply electrical stimulation to the brain, for some reason some days it’s going to go left and some days it’s going to go right.’ And then, in one of those moments when you’re sitting back, and I don’t remember the exact moment, but it all just sort of came together and I realized that on the day it was going left that I was probing the system in one particular way. I was activating one particular pathway. And the other day I was activating a different pathway. It never occurred to me that these two pathways might respond differently to stimulation, but they do! As soon as I discovered that, everything fell into place. Everything made sense. I was able to develop an explanation of how weak direct current stimulation applied to the brain would affect this pathway in one way and a different pathway in another way, and yet a third pathway still another way. And now every experiment could be interpreted based on this one very simple theory. I was very happy with that outcome at the time.” The smile on Bikson’s face when he recounted this story was evidence that the resolution still means a lot to him.

Well, JoJo, that’s just great. But what’s he done lately? I’m happy to report that Bikson is a full professor and the Co-Director of the Neural Engineering Group at City College of New York where he continues electrocuting people. No. Wait. That’s not right, well, not in the way it sounded. Bikson has pursued his interest in how intentional application of electricity can treat different neurological and psychiatric disorders – and now to enhance performance in healthy individuals. He remains focused on non-invasive technologies in order to produce specific outcomes. “My lab studies this at many levels,” he said. “We look at cellular mechanisms, animal models, we use computational models, we develop hardware, and we do human trials. We run the gamut. I think that’s a strength because what you do on one end can inform what you do on the other end. This insight goes both ways across the development process, which I think can give us a unique perspective.”

Bikson also walked me through his Shelley-esque Brain Signal Transplantation project. “There’s a lot of interest in what people are calling ‘brain read, brain write’ so you can record from the brain and then stimulate the brain at the right place and the right time to produce a specific outcome. One version of that read/write or closed loop stimulation is to record the signal coming out from the brain and you essentially play it back; you try to invert it” he expounded. “The idea behind that relates to the fact that the electricity that the brain is generating, which is so strong it can even be measured on the surface of the head, is a marker of brain function – but maybe it’s not just an epi-phenomena, not just a byproduct when the brain does stuff. Maybe these electrical fields – maybe these fields that are generated by the brain are also picked up by the brain.”

He wanted to be sure he hadn’t lost me (close, but not yet) and continued, “The brain is generating electrical signals in one part and it is being sensed in another part and that is called endogenous interactions or field effects. The notion now is that if the brain generates these electrical signals, and these signals have meaning, let’s record them and play them back and the brain will interpret them.” Like an evil genius, he’s duping the brain into ignoring the source of the signal for his own intentions. “The brain doesn’t know that it didn’t generate those particular signals, it just says ‘here comes this endogenous signal and I’m going to interpret it and respond accordingly.” Out of natural humility, he’s quick to point out that his lab is not the first to work on this idea.

The way he explained his brain signal hijacking made so much sense (even to a non-scientist) so, I probed a little further. “What’s in the way of this being a slam-dunk?” I asked.

“Everything! Nothing!” he exclaimed (quick sidebar: have you ever read a neurotech article that ascribes an exclamation to someone? No One in neurotech articles ever exclaims anything. You’re welcome.) “We’re just trying to move things along. Generally, when you’re talking about deploying something that is going to be useful, there are certain things that you want it to do,” said Bikson. “You want it to be effective, but effective also means impactful. There’s been a lot of work demonstrating in the laboratory experimental phenomena following electrical stimulation, this ability to change how people think and how they feel in a lab setting. I think one area that is driving innovation right now is translating that out of the lab into certain more deployable platforms. That’s true of both enhancement of cognitive function and for treatment of diseases as well; we’ve had many clinical trials where we’ve seen encouraging results.

“One of the hurdles of getting things out there in the real world is maximizing the effect size and trying to make sure that not three out of ten, but eight out of ten people respond. For me the question isn’t necessarily does it work or not, but more about how you can optimize it to make it meaningful. That’s where we’re putting a lot of our attention.”

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