 Boom. What's up everyone? Welcome to simulation. I'm your host Alan Sakyan. We are at the transformative technology conference We our mind has been blown over and over and over again. We are now with dr. Bashar Bajran Thank you for joining us. Thank you really appreciate it likewise. Thank you and Bashar is a neuroscientist at the medical University of South Carolina That's correct and You were telling me that you were working on vagus nerve Vegas nerve There's just a lot of stuff that you're doing. I'm excited to learn more about this. Yeah, that's unpack Oh, the transcranial make direct make try transcranial direct current stimulation and TMS magnetic stimulation It's all all of the above. Yeah, so okay, but even before we talk about Exactly what you've been up to most recently. Let's talk about how you even got excited about neuroscience It's like who are you? How did you yeah get? Yeah, so I'm trained neuroscientist from the medical University of South Carolina That's where I did my graduate training. I did it under the direction of mark george Who is known for inventing TMS to treat depression? Whoa, so kind of the pedigree in history of my lab goes back to the 80s And in the 80s was kind of this evolution of using brain stimulation as a non pharmacological intervention to treat neuro psychiatric disorders So really there was two kind of big findings in the 80s One was by tony barker who is from the uk. He's awesome dude He invented a machine that can deliver magnetic stimuli to the nervous system and My mentor mark at the time was training in the uk Saw one of these machines and said hey, we can put this on on the head and stimulate the brain neurons in the brain to treat depression And that's when it all started in the late 80s. It went on to the 90s where At musc they ran all the early clinical trials and developed tms is now an fda approved treatment for major depressive disorder um, and it took about 10 or 15 years of development to get to the point where a company in neuronetics ended up Taking the technology running with it and getting an fda indication for depression. So that Is really a game changer in psychiatry. It's really one of the only non pharmacological interventions for depression There's also one other really cool finding in the 80s was wait. Can we talk about what part of the How we're how exactly of course happening. So tms. It's really essentially a big stack of capacitors Electricity comes in from the wall is stored in these capacitors and then rapidly discharge that a specific frequency Uh through an electromagnetic coil, which is essentially a bunch of copper windings, right? So an electricity goes through these copper windings. It creates an induced magnetic field Magnetic fields a few centimeters And if you put that on the brain on the skull essentially and fire these magnetic pulses at a specific pulse pattern You induce electrical currents in the brain those stimulate neurons and cause kind of a long-term Plasticity that helps treat a variety of disorders for depression. We stimulate the left dorsal outer prefrontal cortex EEG position f3, which is like right here And if you deliver about 10 hertz that's like executive functioning correct cognitive functioning executive control And also mood and so what we do is we deliver tms to that position five days a week for four to six weeks and people that have failed a series of Antidepressants several series of antidepressants. They're really refractory. They come in They see the doc they get treated at the clinic and after four to six weeks They can go back to their jobs and it's and they're fully better. They remit So they come in with really high depression rating score. It's the hamilton rating depression rating score In the 20s high 20s still used hamilton the hamilton depression rating score Yeah, so it's called the hamd hamd and that's used clinically. It's a kind of a clinical questionnaire That's administered. It's not subjective So I would ask you a series of questions and then the rater would rate your depression symptoms interesting Oh instead of self-diagnosing that's that's it's interesting. Yeah, so it's uh, we do this weekly and we track the progress Oh cool. That's how you know that tms is working because yep Oh, because you're at your you have like a psychiatrist that's asking correct questions So the psychiatrist is there weekly evaluating usually it's on like a friday to get the lay of the land and we can track Usually people respond to tms in two to three weeks and they're all the way better by week six Now we're making a lot of advancements on Kind of shortening the total treatment length by doing multiple sessions in a day So we can try to shorten that treatment course from four to six weeks to about two weeks With these kind of rapid Paradigms that we're developing right now and and what are you so now tell us kind of like the exact Uh The exact process for somebody They they come in their hamd score is would it be high or low high they would be high Okay, so hamd scores high and then you say okay We can do tms right here on the left dorsal lateral prefrontal cortex And then we can do that once a day for four to six weeks And then we'll evaluate you midway through and at the end or like we evaluate Weekly and it's really daily, you know The physician's always interacting with the patient and the nursing staff and personnel We're seeing these patients every day and then and then what is what is what is going on? Especially in that left dl pfc area of the brain Like what where are you by stimulating that area magnetically and causing that area to Fire what is Why why is that specifically? Causing them to be less depressed like is it taking attention away from another depressive area or like yeah, how it's a good question You know, there's a lot of different hypotheses on how a depression works. It's still kind of unknown But one of the major ones is there is this uh under activation in Uh, just resting activation in the dorsal lateral prefrontal cortex So a lot of early studies in the 90s were showing that there was decreased metabolism. So less active neurons in the dl pfc that really uh elicited this kind of target But there's also this idea that uh, the dl pfc is part of this larger network With substructures that are deep in the brain like the enterosingulate that are involved in mood and salience, right? So, uh, it's kind of doing a twofold a twofold when we do tms in the fmri scanner So we can actually do tms in the scanner. Oh interesting. It's really complicated and awesome Yeah, we can look at what's happening in the brain in response to a single session of tms And we're creating increased blood oxygenation level dependent signal bold signal Which means that part of the brain in response to the magnetic stimulation is becoming more active for that period of time Slowly goes away the more you do it the longer that effect stays eventually it sticks Now does this potentially have something to do with how When I feel Like I don't have something to like that my executive functioning saying go and build this Aspect of whatever may brings meaning to your life And if I don't have that clicking I kind of tend to go to netflix or facebook or whatever it might be And I might not find as much meaning or fulfillment in life by doing that Perhaps although maybe you're just procrastinating from a task that you really don't want to do So tms doesn't help with that, but People that are depressed really Wouldn't even be able to watch netflix. Some of the patients we see are Staying at home. They've generally quit their jobs They really can't function. Some of them are bedridden and stay in bed. Oh, yeah, that's right So there's this idea or this term called it was a movie on that. Um, I believe it was a I don't think it was a motor. I don't think it was a motor Reason. I think it was a depressive reason. Oh what movie I should remember the name, but it's okay. Yeah, okay So here's the deal. There are these physiological problems that occur within us that cause people to be bedridden Yeah, so eventually that's called catatonia and when you have catatonia you end up actually Being a little too sick to get tms. You end up getting something called ect One of our friends and mentors herald sat time Electroconvulsive therapy. I think that might have been so there's an old movie that kind of stigmatized ect called one One flew over the cuckoo's nest. Yes, right And that actually did I think a disservice to ect because it's really one of the most effective treatments for depression that we have When people come in with catatonia or they're admitted into the unit Ect brings them right back to to step one and you only need about You know 10 or 12 treatments There's about three treatments a week for a couple weeks and they're way better than they started So now be sure where are you amongst everything that you've been describing? Are you Analyzing things and making sure that everything's going well out of the whole So that's a great question. Usually I I'm the one that develops the new paradigms So a couple of the kind of new paradigms we thought is rather than just focusing on the dorsal outer prefrontal cortex Perhaps you can use different cortical Um targets to stimulate networks, right? So the most recent Two developments in tms that I did in my lab was One targeting the pre supplementary motor area, which is right here. That's connected to deep Motor control networks and we did that to treat essential tremor. We also Use that site to kind of detune the obsessional thoughts in ocd So we did that in 2013 and 14 and now that's actually gone to fda approval Now people can get tms for ocd based on that early findings. We do tms paired with an exposure Therapy and it gets people who are refractory In their ocd treatment to pretty much remit. So they get all the way better In ocd. It's amazing. So that's kind of some of the stuff we do in the lab. We have an active Brain stimulation clinic that treats folks from the community That are usually depressed by polar anxious And then we develop the new paradigms, but that's only kind of one third of what we do We also do something called vagus nerve stimulation, which was developed in the 80s by jake zabara who's a friend and mentor In the early 80s, this is a beautiful nerve that goes the vagus nerves awesome It's really this large central bundle of nerves It runs from your brain all the way down and targets every smooth muscle organ in your body Stomach, heart, lungs, spleen, kidneys, intestines, bladder All of it. Wow. So your eyes allow you to see What's in front of you and what's in this room and I could look out and there's someone swimming in the pool But your your internal organs need to communicate with your brain too And the vagus nerve is how they communicate with the brain kind of like how your eyes communicate with your brain with the optic nerve That's what the vagus nerve is for and if you look at all the high way high way of communication Yeah, it's really a super highway and it's this bundle that can target all of these nerves It's a majority of your daily life functions that you even don't even know that Or that are on these are the autonomic. It's an autonomic nervous system nerve It's really associated with the parasympathetic nervous system Or the slowing of bodily functions. So there's really two Autonomic control systems the sympathetic which is really your fight or flight and gets you up and stressed and ready to Evolutionarily escape from a stressor With the parasympathetic, which allows you to slow right go to sleep relax your heart rate Digest and so those are cholinergic So acetylcholine is the neurotransmitter associated with this pathway the vagus nerve Dumped acetylcholine onto these organs and it causes a relaxation and slowing that process starts at the brain Acetylcholine is the neurotransmitter that the vagus nerve dumps into the Onto the organ for the For the parasympathetic nervous system functioning correct, but that is initiated in the brain So before it dumps any type of neurotransmitter. Yeah, there is a complex system that's uh Uh initiated kind of in these deeper brain structures that then send the signal out to the vagus nerve So then there's like there's this from the brain. We go down. There's all the the cerebral spinal Neural system and then there's also the vague vagus nerve system. So it's gonna. Yeah, the vagus is in Your thorax, so it's in your in the cavity in your body's cavity. It doesn't initiate in the spine. It's wandering So vagus. Yeah is lack is Latin for wandering for wandering So it's it used to it was called the wandering nerve and i'll show you in my talk later today that It was there was this italian uh neuroanatomist that dissected the body in the 1500s It's this beautiful image of all the nerves in the body spine and you can see the vagus nerve is literally The the most complicated part of the entire thing and so that's where it got its name as the wandering nerve because it just travels throughout your body And what's interesting is there's not only uh efferent effects or from the brain to the body, but you can actually Go from the body to the brain, right? So it's bi-directional communication And we can take advantage of that by stimulating it to access deep parts of the brain Okay, now teach us about how to stimulate the vagus nerve and what it does. So in the early, um, well, actually it's really late 1980s there was a neurophysiologist jigsawara who had a epileptic dog model so canine dog that had epilepsy he implanted the electrodes onto the nerve directly of the vagus nerve and when he turned on electrical stimulation externally internally internally Okay, so you do the dissection. Um, and you access it really kind of in the Cervical part of your neck. You can't do external stimulation of vagus nerve That's what you can and that's what we've been developing. Okay. Sorry. I jumped the gun. Keep going. Yeah But all of the early studies were implantable. In fact, uh, when you turn on electrical stimulation onto the nerve You stop the epileptic waveform stops epilepsy. So that's where vns started Uh, and from then on jacus nerve simulation. Yeah, so the vns Uh, actually jake, uh, interesting fact that not a lot of people know is that he called it a neuro cybernetic prosthesis but the The medical community community didn't really understand that and they changed the name to vagus nerve stimulation So initially it was ncp Which then became vns. I like ncp better, but vns is cool and it's stuck So, um, that ended up becoming a company that jake founded called cyberonics Um, and over 150,000 people across the world have been implanted with a vns stimulator to treat their refractory epilepsy Whoa 30 to 40 of people implanted have reductions of More than 75 of their daily seizures that didn't respond to meds. It's amazing So just a little electricity here Um, actually ends up stopping your your seizures. Yeah, and then from then on there was actually A really astute and this is like a cool history lesson and astute Um, hotel clerk that noticed that these patients that had epilepsy Uh That were coming to stay for follow-up visits their moods were getting better and he reported it to one of the docs That's cool. They they they then explored vns to treat depression and it treats depression Whoa, so it became this, um, epilepsy treatment depression treatment recently It's been FDA approved for chronic morbid obesity So if you plant stimulators at the level on the on the vagus nerve right above the stomach Yeah, uh, it decreases your appetite and reduces obesity symptoms so people lose body fat That sounds a lot better than the bigastro bypass surgery Well, in fact when people get their stomach stapled for those types of procedures sometimes in rare cases Um There's a mistake and they actually staple over the vagus nerve And if you damage the vagus nerve all the downstream communication for the vagus becomes interrupted So it's actually pretty risky. So that I mean these are all the developments, but You can't really implant everybody to try out a bunch of stuff. It's expensive because about $50,000 You have to go into the or and do it any surgeon trained in head and neck dissection can do it but It's not really common for individuals that are exploring you for other things So what my group's been doing I've been doing a lot of research on this in the last five years Is developing non-invasive vagus nerve stimulation So rather than implanting electrodes, you can stimulate a branch of the vagus nerve that innervates your ear That's called the auricular branch of the vagus nerve And you can use electricity to stimulate that nerve and mimic the effects of implantable Which now has opened up this entire field of vns to everybody It reduces heart rate. It increases heart rate variability. It treats depression It doesn't work super well on epilepsy, but that's because it's still early and the dose isn't optimized But where where does the electrode go externally? So the electrode goes Uh in your ear. So you can stimulate the auricular branch of the vagus nerve either in the left or right ear And this small little off branch of the main bundle Can be targeted in your ear right in there's a couple different targets One is the anterior wall of the external ear canal So like your tragus, but on the backside of your little tragus Or you can target the simbaconsha, which is this kind of top part on the inside Circle of your ear or you can target it on the mastoid. Whoa, and you can just You can is that um, is that an electrical stimulation electrical stimulation? So we A long time ago, they tried to do magnetic stimulation there But it's uncomfortable to deliver magnetic pulses there because there's a lot of muscles So what we thought was perhaps we can do electricity to mimic it. We started these studies in 2013 And we explored the entire parameter space so low frequency high frequency big pulse width long or short pulse width Long stimulation short stimulation different electrodes different different targets and over the years We've optimized this technology and now it's rolling out into several clinical trials across the united states So this is all at m u m u s c. Okay, and how long has it been that you've been doing that there six years six years there And then you have a lab there. Correct. And what's the lab called? So it's the brain stimulation lab brain stimulation lab correct How many people are in the lab right now? The lab is pretty big. So we have around 20 staff 20 staff We have the division director mark george who's still around we have Three other faculty there who do a variety of things from a nervous stimulation to treat addictions PTSD working with veterans There's a really interesting individual dr Shing Baoli who does tms for smoking cessation Nice works really well to help people quit smoking which is a really big problem in the united states Well, this list is crazy. Okay. So helping with smoking helping with addiction helping with PTSD helping with With potential stumps the gas hunger It's pressing soft But I think what the most cool part of the entire thing is besides all of these by the way, we're doing parkinsons With vagus nerve stimulation But the most interesting that the project is that i'm doing with dr. Doe jankins who was a pediatric neonatologist using non-invasive vns paired with Bottle suck training. Wow In pre-term neonates to accelerate the learning of how to feed And put down formula To be discharged from the hospital faster when they're born with a hypoxic ischemic event And what's the hypoxic ischemic event that prevents them from being discharged? So before the when the babies are born either pre-term or out-term but with Essentially a brain injury where they lose oxygen to the brain They don't have the ability to feed on a bottle So what they do is they stay in the nursery with their family for up to six weeks And they're trained how to use A bottle suck on a nipple and put down food if they don't put down food They get discharged with a gastric Gastric tube a gi tube wow where the mom then has to feed the baby through a port in the stomach So what we thought was we can take advantage of this vagus nerve which also enhances Kind of a global meta plasticity We pair vagus nerve stimulation with Training and rehabilitation on how to feed with occupational therapists And the babies rather than waiting six weeks and then getting a gi tube Over half of them are discharged without a g tube And they could discharge way faster. So between 10 and 20 days rather than six weeks. Yeah. Yeah So that's really the most promising work at musc Yeah, and so that just got published recently as a brief report now We're doing the larger clinical trial. Yeah, and how many children are born with that inability to to suck on the nipple You know, I'm not too familiar with the percentages. Okay, but It's pretty common and these a lot of the babies that are born pre-term Don't have this ability. So even if you don't have the hypoxic ischemic event A lot of babies are candidates for g tubes because they just can't learn how to feed Now you don't hear about a lot of these cases. You really hear about the healthy ones Oh, I had a healthy baby And it's doing great But there's a lot of babies in the unit that have this difficulty feeding and get sent home with a surgery energy tube Wow, um, holy cow. Bashar. Um, I am so Impressed there's so much so much different stimulation that can occur electrically magnetically to solve so many different it Problems that exist in in humans that that I think can help create a healthier happier civilization That's oh, yeah, and you're you're investigating into all of these right now We test all of them and what's really Fascinating is that these technologies end up trickling down to people like me and you so we take these treatments that help people And treat disorders Then we investigate how they can help us in our day to day life One of the prime examples is what I was telling you earlier is using tdcs It's this low electrical current stimulation about two milliamps that runs off a small 9 volt battery. It's pretty cheap and inexpensive We use that to help people feel calm and relaxed And accelerate their meditative practice So that was something that we used to research for pain and cognitive enhancement Has now trickled down into a paradigm called e meditation that came out of MUSC as well And we use that we were actually demoing it here at the conference There is 40 people in vermont that are doing the first ever brain stimulation Retreat where they meditate At a monastic center for five days using brain stimulation to augment their meditation practice It's really cool stuff. So that method's called e meditation I've been thinking about that for a while because whenever I go to the 10 day meditation retreats They just came back from one. I I always love the idea of thinking how to augment it 2,500 years ago when this is you know conceived this isn't really we didn't have the Like tdcs and we didn't have Access to so many like other psychedelics that we could you know So there's so many different ways to kind of add variables to the meditation mixture to just see what happens Yeah, yeah So what you know, we what we know is safe and we know actually works in the sick brain Is now coming to individuals in the healthy brain to optimize human performance and help help us connect to interact with each other And hopefully make a better world one day if we can all Connect with each other and and be kind to one another through these really transformative technologies like e meditation We can really change the world and that's what we've been developing at MUSC It's really exciting. So that's the stuff that gets me out of bed every day Is is doing the whole gamut of brain stimulation and hopefully one of these things will be able to be used in the general public To improve day-to-day life I love it. You are amazing. You're amazing. Thank you So I'm so grateful to have been able to interview you I think there's a lot of cool collaboration explorations we can do with an organization called Brain Mind We'd like to potentially loop you into that as well as You know the neuro scape over here at adam gazelli's Lab over here. Great. There's a lot of cool stuff to explore. So I'm again super grateful for you. Thank you so much Hey, no problem teaching us about everything you're up to. Thanks for having me. It's really cool. Your story's incredible And what you're working on is amazing. So thanks everyone for tuning in. We greatly appreciate it We'd love to hear your thoughts in the comments below Also, go and build the future go manifest your dreams into the world everyone. Thanks for tuning in much love That was so fun, man. You are you are you are rock star