Revolutionizing the Training of Medical Professionals Insights from Neuroscientist Nicolas Gninenko

Episode Overview

Episode Topic: In this episode of Skeleton Crew – The Rad Tech Show host Jennifer Callahan interviews Nicolas Gninenko, a clinical neuroscientist at Neuro Soft Bioelectronics. The conversation dives into the innovative field of neurological technology, exploring the development and potential impact of soft, flexible brain implants. The discussion highlights the company’s work on implants designed to address severe neurological conditions such as tinnitus and Parkinson’s disease. The episode provides a comprehensive look at the cutting-edge advancements in brain modulation and the potential benefits for patients suffering from chronic neurological disorders.

Lessons You’ll Learn: Listeners will gain insight into the latest advancements in neurological technology and the development of soft, flexible brain implants. Nicolas explains how these implants can be used to alleviate symptoms of severe conditions like tinnitus and Parkinson’s disease. The episode also covers the rigorous research and development process involved in bringing such groundbreaking technology to market, including the challenges of achieving FDA approval. Furthermore, the discussion sheds light on the potential of noninvasive brain modulation techniques and their effectiveness in enhancing brain plasticity and reducing the burden of chronic neurological conditions.

About Our Guests: Nicolas Gninenko is a clinical neuroscientist at Neuro Soft Bioelectronics, a company focused on developing soft, flexible brain implants. With a background in noninvasive brain modulation techniques, Nicolas has been instrumental in advancing research aimed at alleviating chronic neurological conditions such as tinnitus. He holds a PhD from EPFL in Geneva, Switzerland, where he conducted extensive clinical trials demonstrating the effectiveness of neurofeedback in reducing tinnitus perception. His work at Neuro Soft Bioelectronics involves exploring minimally invasive approaches to brain stimulation and improving the quality of life for patients with neurological disorder.

Topics Covered: The episode covers a range of topics, including the development and application of soft, flexible brain implants by Neuro Soft Bioelectronics. Nicolas explains the technology behind these implants and their potential to address severe neurological conditions like tinnitus and Parkinson’s disease. The discussion also delves into the research process, the challenges of achieving FDA approval, and the differences in regulatory requirements between the US and other countries. Additionally, the episode explores the use of noninvasive brain modulation techniques, such as neurofeedback, and their role in enhancing brain plasticity and reducing the burden of chronic neurological conditions.

Our Guest:  Nicolas Gninenko’s Role in Neuro Soft Bioelectronics

Episode Transcript

Jennifer Callahan:  Hey, everybody, welcome back to another episode of The Skeleton Crew. I’m your host Jen Callihan. And today I have a great guest with me. His name is Nicholas.  he is a clinical neuroscientist at a company called Neuro Soft Bioelectronics. And today we’re going to switch roles. And instead of talking about, you know, bones and, and AI and things like that that we have been talking about most recently, , we’re going to be talking about the neurological field. So definitely a little switch up and maybe something a little bit more interesting. I was telling Nicholas that, you know, it definitely caught my attention because I worked at a hospital for a while that had level one trauma with neuro. Excuse me. Neurology there. So very interested to hear about what their company is doing. Nicholas, thanks for being with me today.

Nicolas Gninenko: Thank you.

Jennifer Callahan: All right. So let’s get into it. Let’s kind of just talk about what the company is doing, , and maybe how you landed there  with everybody there.

Nicolas Gninenko: Yeah, absolutely. So the company was founded about four years ago by my colleagues. So Nicholas and Ludovic Zarek. They both did their PhD work here at, , EPFL. So it’s the Swiss Federal Institute of Technology, and they worked mainly on this new generation of implants of electrodes. So that from there is an was born a soft bioelectronics. So which is a company where we develop soft, flexible implants directly aimed to be positioned on the surface of the brain. And so on my side, I actually worked more on a specific clinical indication, which is tinnitus, which is a chronic ringing in the ears. And we have shown that with noninvasive brain modulation techniques such as neurofeedback, we can help patients to , to reduce their tinnitus perception. And this is how I reached also with Neurosat, because there is an idea to explore this, , with minimally invasive approaches.

Jennifer Callahan: Okay. Now the implants are going onto the brain. And if you can speak to the the full depth of this, please just say so. But , in the they’re placed onto the brain. , and then is there like, , a pack that’s placed somewhere else within the body to control the electrodes?

Nicolas Gninenko: Absolutely. Yeah. So the electrode is one part of the system. So it will be placed on the directly on to the brain surface, and then it’s connected as a form for example, deep brain stimulation for Parkinson’s. They also have what we call an IPG. So it’s an implantable pulse generator that is placed usually in the chest or in the abdomen, depending on the application. So this IPG serves as a stimulation provides the power to to actually stimulate the brain.

Jennifer Callahan: Okay.

Jennifer Callahan: And then that can be changed externally. Right. Like if they need to change, you know, I guess the signals that are going to the electrode.

Nicolas Gninenko: Yeah. Absolutely. So recent models are allowed to also change this remotely or through the skin. And you can have different kinds of models that also allow recording and stimulation. For example,

Jennifer Callahan: It kind of reminds me of, , I’m not sure if you’ve ever seen before, you know, the stimulators that are placed in the back. , sometimes they’re in the lumbar region, sometimes they’re up in the thoracic region. And then the I don’t want to say the battery pack, but I guess the pack that controls it, , is usually somewhere down along the sacr. , and patients have to come in periodically to get them checked and make sure that the electrodes are still, , or the stimulators, I guess I should say, are still in the area of where they originally implanted. , again, if you can’t speak on this, just say you can. But is that something that would have to be checked periodically with patients that have the electrodes placed on their brain?

Nicolas Gninenko: Yes, I think it’s a separate component. So the electrodes can remain on the brain. But this also actually needs to be checked, as we have seen with recent news from Neuralink as well. So we don’t know if electrodes can stay really located for a very long time, for years. I mean, with this new, , types of electrodes that are basically not, , inserted into the brain but are just placed on the surface. And the separate thing is the IPG, indeed, that needs a battery replacement every couple of years. But this is something also that is improving.

Jennifer Callahan: Okay.

Jennifer Callahan: , I was reading on the website that the placement of the electrodes and, , interesting that it doesn’t go just directly on to the brain, that it can be placed within the folds of the brain as well.

Nicolas Gninenko: Yeah, exactly. That’s why , so that’s why the advantage of what we develop here at Neuro Soft is that we have a, , much thinner and softer 1000 times softer electrodes. That is current. That is , compared to what is currently on the market. And these allow us to reach areas of the brain that are, , deeply buried in the sulci. Indeed, because the brain is a highly folded organ. Right. So sometimes for some applications, you need to reach deeper so we can do that with this kind of technology.

Jennifer Callahan: Now developing this, , I’m sure that there had to be, , like a slew of research that went into it. And I know that this is kind of, you know, where your forte is. , can you discuss with us, you know, maybe the trials that you had to go through or not trials. But, I mean, like the timeline of, you know, were you with everyone in the beginning when this idea came to light and then, you know, going through the different research of it?

Nicolas Gninenko: Yeah. So I come from more a noninvasive technology. So we had this big study with tinnitus patients and with fMRI neurofeedback. So it’s a technology that allows patients to gain, , to learn how to control certain brain activity. So you actually provide feedback from the brain , using the MRI. So you measure activity in the brain and you provide it on a screen as a kind of feedback. And patients can learn to then with different cognitive strategies, they learn to regulate this activity either up or down. And this is interesting because it shows that, , we can enhance some, to some extent, the plasticity of the brain through these kind of methods as neurofeedback. And this is relevant for the invasive approach because if you place directly electrode sensing the brain, you have much better signal and much faster signal quality compared to fMRI, for example, or EEG than the noninvasive alternative. And , this can enable a new range of applications with new stimulation paradigms and closed loop  paradigms for for patients to to learn how to modulate their activity as an alternative to brain stimulation as well. 

Jennifer Callahan: , so the stimuli that you’re talking about during an MRI, is that something that’s being done to the patient as they’re on the table or.

Nicolas Gninenko: Yeah, they’re laying in the MRI scanner and they receive direct feedback. So they have a mirror so that they can see a screen. And on screen you display their brain activity, simply speaking. Yeah.

Jennifer Callahan: Gotcha. That’s what’s interesting. , so you were saying that the electrodes currently right now are, you know, they’re not out on the market just yet. , but you had said Parkinson’s and tinnitus. , now I’m assuming that, you know, in the beginning of the research, you know, we had discussed that you had said that, you know, using, you know, mice and rats, , and monkeys are are these animals actually having these types of, , not diseases, but, you know, do they have Parkinson’s or do you know, do they have tinnitus? Is that something that you can measure?

Nicolas Gninenko: That’s that’s a good question I can so about tinnitus, it’s it’s, , there are models of, , of tinnitus induction in, in animals. Indeed. , you can overexpose them to to very loud noise or induce it through medication. But of course, they don’t have the subjective component so that the animal will not be able to tell you to report on his perception. Right. And so there are also, , methods to, to assess that, , with intraneural recordings in.

Jennifer Callahan: Animals.

Nicolas Gninenko: But we lack a little bit this there is a gap between animal research at least 14in and han that’s for sure.

Jennifer Callahan: Yeah.

Jennifer Callahan: , now Nicolas was telling me that, you know, like I had said, there’s still, , not out on the market. They still have to go through the FDA approval. , but so what, what’s the timeline there for you all? , you know, you’re doing the animal research and then from there, are you looking into going with hands and then going for the FDA approval? I’m assuming you have to have X amount of studies done or you can go for approval.

Nicolas Gninenko: So we are indeed , going for the FDA approval for the first technology we have, which is , called soft ECoG. So it’s, , for monitoring epilepsy and potentially brain tor surgeries and this technology is within. So within the pipeline of the FDA we expect within , 2 to 3 years probably to be on the market for that. Yeah.

Jennifer Callahan: That’s great. I’m sure that’ll be like some groundbreaking, , technology out there for, for patients that are experiencing things like that, especially like, I mean, Parkinson’s and epilepsy. I mean, I can’t even imagine having tinnitus. You know, I was reading about it last night, , and something I’ve heard of, but I just couldn’t even imagine having a constant ringing in my ears. You know, depending on, I’m sure it could be a low h. It could be extremely high. , but anything that could help because they are symptoms that you can’t measure, you know, so you’re just going off of what the patient is saying or can you measure it? Is that something that can be measured by an EEG or something?

Nicolas Gninenko: So we have different approaches. There is indeed the imaging approach for which you can measure some correlates of the tinnitus. But you’re right there is no objective measure today that is really precise and relevant to characterize tinnitus in in a person. But we most studies they rely on on subjective assessment. So then you kind of characterize the tinnitus tinnitus associated distress and burden and not the, the loudness itself. But however we can still do some audiometry. So we, we assess the tinnitus in a, in a quiet booth by, by looking by trying to, to match it with frequency and loudness. And this is one technique that is not, again, an objective measurement because the patient still reports, , whether he hears they hear or not, , different tones. But then it allows to still characterizes on a, on a spectrum of frequency and loudness.

Jennifer Callahan: Okay.

Jennifer Callahan: , are there other, , neurological diseases that, that you’re looking to, to, you know, branch into or are you looking at specific ones right now until you get your clearance?

Nicolas Gninenko: So we I mean, there is a broad ranges of, of neurological disorders that could be addressed with, with this technology, including, I mean, for example, diff deafness or blindness or other motor severe motor disorders. We also have something with spinal implants. So you can simulate the spinal cord as well with this kind of technology. So here you have a, you know, a whole range of, of pathologies that can be, , potentially addressed.

Jennifer Callahan: 

Jennifer Callahan: You seem pretty passionate about the field.  what did you do before you got in with neuro soft.

Nicolas Gninenko: So we, I did my PhD thesis at EPFL here in Geneva in Switzerland. And we looked we did a large clinical trial with tinnitus patients, moderate to severe tinnitus patients. And we indeed show we have shown that fMRI neurofeedback and EEG neurofeedback can outperform, , the classical cognitive behavioral therapy. , that is actually the most recommended treatment and most widely, , prescribed treatment for tinnitus. But there is no cure for tinnitus. So what we have shown is that these technologies non-invasively can reduce the perception better, at least the associated burden better than a cognitive therapy. So it means that there is some kind of self involvement from these patients into the neurofeedback paradigm that they can learn to, to reduce their own perception. And this is an interesting result for all the field of invasive or minimally invasive interface.

Jennifer Callahan: , so lots of stuff going on there. Very, very, very involved. , did you have you guys, , come across any, like, roadblocks while you’ve been in the midst of developing this? You know, whether it’s research wise or, you know, externally?

Nicolas Gninenko: Yes. It’s a long path because you there are many mechanisms that need to be probed at least. And there is also a gap between, let’s say, the pace you can achieve in the research setting and in the, you know, on the market. So, , let’s say we face a few challenges with, with our, , with moving fast. But I think that the team here is making a great job so that we made significant progress in the last four years. Three, four.YEARS 

Jennifer Callahan: Do you have new members joining the team like here or there or have you all been together kind of since inception.

Nicolas Gninenko: I joined the two and a half years ago and the startup was created about four years ago. So I joined a little bit later. But now, yes, the team is growing. We are about 15 people and , yeah, there’s much, much more to do.

Jennifer Callahan: , so the clearance, you said FDA approval, are you talking for , the United States or are you guys looking for, you know, Europe or, you know, other, other areas?

Nicolas Gninenko: , mainly we, we mainly focus on, on the US market. That’s true. But we also look at different other opportunities.

Jennifer Callahan: Yeah.

Nicolas Gninenko: That’s that’s, , it depends a little bit on, on the regulation processes in other countries and , yeah, that’s.

Jennifer Callahan: If you don’t.

Jennifer Callahan: Know this answer, please just say it. But are there are are the regulations in other countries. I mean, I’m sure that they differ from the United States, but is one more stringent than the other? Do you know?

Nicolas Gninenko: I think in the US, it’s it’s true that it’s probably slightly easier to get on the market with invasive or highly invasive technology. In Europe, it’s maybe a bit more regulated. Recently, also with the new revision of the medical device regulations. But in general, I think that they I mean we have also other markets that we can explore outside of these two.

Jennifer Callahan: Okay. All right.

Jennifer Callahan: . So just thinking about the electrodes themselves and having being placed directly onto the brain. , I mean, it sounds like it could be kind of rather, you know, it’s an invasive surgery, you know, like, I’m assuming you have to cut through the skull. Correct. And then to have them be placed onto the brain or into the folds of the brain. , where did you guys, you know, where is the thinking that going the more invasive route as opposed to like the less invasive route or non invasive route, you know, what’s the backing behind that or the benefit I guess I should say or ask.

Nicolas Gninenko: Yeah, it’s a good question. What we show is that with the noninvasive approach, we can achieve a certain benefit for these patients regarding tinnitus in particular. And, , but we have some evidence from the past 20 years of, of, , there has been very scarce studies of, , invasive modulation for tinnitus in very severe cases. And actually some of these studies, more like case reports, have shown that this is possible to fully suppress the percept. So achieving an even better clinical outcome than what we did with noninvasive technology. Right. And so this is the rationale for very severely affected individuals. We would like to try to fully suppress the tinnitus and to reverse these pathological brain networks.

Jennifer Callahan: Okay.

Jennifer Callahan: Again, if you can answer this, it’s totally okay. But the surgery that a patient might potentially have to go through to have this done, , is it like removing a portion of the skull, or is it cutting part of the skull off and putting it back on? Or I have all these images, like floating through my head.

Nicolas Gninenko: Okay, it’s also a good point. , we of course we are aware that not not everyone wants an implant, right? , especially that it’s very invasive as a procedure. So we are working also on the minimally invasive strategies to, to put that in place. So you might go from large craniotomy so you don’t remove any more. A big part of the skull. But instead of that, you just drill what we call burr holes, for example. Okay. , to have very, very small holes, , through which you can deploy or insert, , our, our electrodes.

Jennifer Callahan: Okay.

Nicolas Gninenko: And that would significantly reduce the impact of the surgery as well.

Jennifer Callahan: , question that did just pop into my head thinking about, you know, where you know, where it would be implanted, you know, if you did have to do craniotomy. , what imaging are you using to figure out what part of the brain that these electrodes need to go on to?

Nicolas Gninenko: So we we basically use a lot of, , MRI, , functional and structural MRI and CT. We we can use CT in the, in the intra interest of setting to verify that we actually place the electrodes at the correct location. Yeah.

Jennifer Callahan: And then I’m assing too, I mean, that certain parts I mean, it’s probably so much research has already been done that certain parts of the brain are affected by certain disorders. Right? Don’t they say or not? Not don’t they say I could be very wrong. Isn’t like your personality and like your frontal lobe or, you know, certain things or. You know what I mean? Like certain part of your bodies are controlled by different parts of your brain. I apologize. I do not know much about neurology.

Nicolas Gninenko: No. It’s fine. So there’s been extensive research into into looking in. Indeed. At which location? In the brain, , you may want to place, , such, , interfaces. And 14in is not obvious. Of course not. Not for any disease, but for example, for Parkinson’s is now, , more and more established that, , which targets should be, should be, , , targeted with deep brain stimulation, for example, to reduce the tremors. Right. However, for 14 to it’s a novel direction. So it’s, , what has been done is mainly on the auditory cortex, on the temporal regions here. But we also have today, we know that there are more regions of the brain that are involved in chronic tinnitus. And so therefore we can, , adapt the technology to also reach those.

Jennifer Callahan: Okay.

Jennifer Callahan: , are there disorders that I mean, I know that you’re focusing on, you know, a few specific ones right now at this point. , but how you were saying that, you know, for the tinnitus, you know, looking at here, , with some disorders require the electrodes to be placed on multiple different parts of the brain. So maybe, like, you know, here and then up here or here and here for maybe tinnitus on both sides of the temporals.

Nicolas Gninenko: Yes. That’s a that’s a good point. So the, the indeed there has been, , at least one case in which they placed, , consecutively two, two electrodes. So one on the auditory cortex and one, , actually was a calf electrode behind the neck on the cervical nerve, which is not the brain, but still and this case has shown that we there are different aspects of tinnitus. So there are different frequencies we can suppress with different locations and stimulation paradigms. So this indeed shows that there is likely that. , several locations are needed to be, , accessed to, to fully, , suppress the tinnitus.

Jennifer Callahan: , and then after these electrodes are placed, is it something that’s checked with like. Mri again or, or Cat scan, you know to see. Or are you basing you know the. I’m trying to think of what the what I want to say, , basing the, you know, information off of me, maybe patient feedback or, you know, will be based off of patient feedback or we use, you know, imaging as well to determine if it’s working.

Nicolas Gninenko: No, it’s mainly based on imaging because you need to verify Preoperatively and also postoperatively whether it’s correctly placed on the right anatomical target. So there is a careful planning and then neuronavigation can be used. So it’s a technique that allows you to see more or less in real time where you are placing the electrodes. And then of course it’s verified again with imaging. Yeah.

Jennifer Callahan: Right. All right.

Jennifer Callahan: Super interesting conversation with you today, Nicholas. I really appreciate your time with me, everybody. Nicholas. , from Norris Bioelectronics doing some awesome work, , to help those out there with neurological disorders. , and hopefully that, you know, this hits the market in the next few years, you know, and can help out those that are going through, , these disorders that, you know, can probably be extremely debilitating. , I mean, Parkinson’s alone, the way that it progresses, we’ve seen, you know, celebrities and things. And I’m sure, you know, people in our audience might know people with Parkinson’s, but, you know, again, tinnitus that Nicholas spoke on, , extensively about something that maybe you don’t even think about. So thank you, Nicholas. I really appreciate it. Interested to see, you know, what happens in the next couple of years for your company.

Nicolas Gninenko: Thank you. Thank you very.

Jennifer Callahan: Much.

Jennifer Callahan: All right, everybody, we’ll see you next week. Have a great week