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'I'd like to be a rockstar'

More often than not, people that want to be rock stars are generally those that crave attention, acceptance and recognition. However in this circumstance I think the attention would simply be a by- product of the pure catharsis of synchrony and good music, with good people.

Jumping online for a teleconference on an early Saturday morning in Melbourne, I couldn’t help but reflect on the state of the current global climate. It’s seven degrees outside, the world is in disarray, and I’m not quite adequately caffeinated. It was late afternoon in Chicago, and warm.

Professor Jay Shils is the director of intraoperative neurophysiology at Rush University Medical School, and the past-President of the International Society of Intraoperative Neurophysiology (ISIN) and the American Society of Neurophysiological Monitoring (ASNM). Jay is a highly recognized researcher and co-editor of ‘Neurophysiology in Neurosurgery’ with Dr Vedran Deletis, and ‘Essential Neuromodulation’ and ‘Innovative Neuromodulation’ with Dr Jeffrey Arle. The prior is one of very few hard-copy editions I’ve owned.

Jay is headed into the July 4th long-weekend. Naturally, the global pandemic is addressed as we exchange pleasantries, but very quickly the conversation resembles one of excitement. Amidst the chaos of a COVID-world, research and development in clinical neuroscience continuous to prosper as we gravitate towards frontiers of technology where therapeutic challenges are surpassed and outcomes previously thought to be impossible are showing promise. Unrelated to these developments, we start with apples.

‘I grew up north of New York City, in a suburban area. We had apple farms and farms. It’ wasn’t fully country, but it wasn’t fully city either…there were a lot of big apple farms in our area. I had a relatively normal upbringing – my father was a physicist and computer programmer, my mother was a teacher.’ It would be presumptuous to conclude that he was destined for a career in science, though Jay is quick to note, ‘I grew up with a poster of the periodic chart of elements on my wall when I was a baby, in my room…and (my parents) bought me Gray’s Anatomy for my sixth birthday’.

Equally, though, Jay was interested in music as early as kindergarten. ‘I started with the violin, then went to trumpet, to piano I learned on my own, guitar I learned on my own but it was really the tuba was what, believe it or not, I spent most of time with.’ To this day, as it quickly becomes evident, he is still interested in playing music. I’m speaking to Jay in his office, where several guitars, a keyboard and an electronic drumkit is visible in front of a well-stocked bookshelf. As an aficionado of music myself, it’s an aspirational office goal, for sure. Towards the end of our conversation, I ask Jay what he might be doing had he not gone down the clinical neuroscience pathway; ‘I’d like to be a rock star’.

Despite his dreams of rock-stardom, Jay was drawn towards electrical engineering at Syracuse University, and went on to complete his Masters and PhD in bio-engineering in the early-1990’s at the University of Pennsylvania, exploring ‘the bispectrum of the human electroencephalogram’ and the interactions in the human visual system and epilepsy.

“We decided to go and look at higher-order spectral analysis where the standard power spectra just looks at the first order energy distribution across signals. Higher order spectra starts asking the questions: if I have a peak, or if I have a frequency of 1, or a frequency of 2, are they related somehow? Or are they completely independent. And if they are related, what’s the non-linear model that relates those different frequencies. So we wanted to use that in seizures to see if there was a way we could predict the onset of seizure using those tools. It did not work out so well.

“We also decided to look at the visual system, and see from the EEG if we could determine where the first point in the brain that the left and right fields actually communicate. We know that anatomically, but could we use the EEG to be able to figure that out also. And that tool did prove to be very helpful to be able to do that.”

There are a number of groups around the world currently working to build implantable devices for the detection and subsequent prevention of epileptic seizures. In addition to the radical interventional therapeutic benefits of such devices, it’s also a potentially lucrative industrialization effort, with approximately 50-million epilepsy patients around the world.

“I think that there are certain markers for seizures that are pretty accurate. And if you look at certain types of seizures, particularly the temporal lobe type of seizure, there are some markers there that are a little more predictable than others. It’s a little bit more individualized. In fact I think where we’re going today with this, I think that with these closed loop systems we’re working on generally for neuromodulation – is looking for individualized therapy, where the system learns something about that particular patient and adapts. What I was looking at was a little more global, it wasn’t too specific to the type of seizure. I think that’s where the big problem was with it. But as we’re getting more and more processing power over time, we’ll be able to implement individual therapies in humans.”

Towards the end of his doctorate Jay developed an interest in the surgical applications of clinical neurophysiology, where he was exposed to intracranial EEG monitoring and mapping used during the surgical treatment of medication-resistant epilepsy. “I was in the clinical neurophysiology lab, which was where I did my work, and was also at the epilepsy center. And so, I got interested and said well maybe I’ll just go in there and start playing with this and see what comes of it.”

The parallels between clinical research undertaken in the confines of a laboratory compared to the sometimes-unpredictable nature of the operating rooms are sparse. Given Jay’s engineering background, though, there’s a natural inclination towards the manual exploration of science. He insists that it was the ‘hands-on’ aspect that drew him towards intraoperative neurophysiology. “As an engineer,, during my short period of engineering, I was in the reactor plant planning yard, – kind of the service station for submarines. We were hands-on on the boats, solving problems. Intraoperative monitoring was hands-on experience in the operating room, where else can you gather data on a human brain on a daily basis? It’s very rare.”

Having spent the majority of his career in clinical neurophysiology exploring microelectrode recording (MER) in movement disorder surgery, the advent of robotic and advanced imaging technologies are a topic of interest. Deep Brain Stimulation (DBS) surgery is most commonly conducted with the patient ‘awake’, so as to maximize the therapeutic benefit of the implanted electrode, which is designed to counter the debilitating clinical effects of disorders such as Parkinson’s Disease.

“My career is based on doing awake MER recordings, but that was in a time where technology was not that far advanced. Imaging was pretty poor, our understanding of the systems were a lot less than we have now, our understanding electric fields in the brain were less than we have now. But there’s now this push, as you said, to go completely to the other side of the coin, completely asleep with pure imaging, and I think people forget that it’s not only an anatomic target we’re looking at. It’s a physiologic target. Different aspects of that anatomical structure, if you put the electrode in the wrong place, it doesn’t work as well or actually hurts the patient at that time.”

“There has to be some kind of medium between the two of them. I think we are going to be seeing a lot more cases asleep. But I do think that we as the IONM community need to come up with technologies and techniques that can still be used during those procedures. And that’s actually where some of our new research lies now: how can we make neurophysiology have an impact on these procedures and (development) of new technologies.”

There are early signs of a paradigm shift, and the researcher in Jay is enthusiastic. “The team probably puts in about, maybe, 100+ leads a year at Rush. When I first started almost 25 years ago they were almost 100% awake. Now it’s probably about 50/50. It’s shifted quite a bit. I’ve recorded MER in asleep patients prior to my time at Rush, and there are very specific challenges that come with that. The firing patterns are significantly different, they’re even anesthetic dose-dependent . It’s much more complicated to make a differentiation between targets when they’re asleep versus when they’re awake. Multiple areas of the asleep brain tend to sound similar.”

Prior to electrical neuromodulation, surgical ablation or lesioning of ‘hyperactive’ structures was the primary surgical therapy. Momentum for the surgical treatment of deep subcortical structures of the thalamus was stalled when Parkinson’s miracle drug L-DOPA was introduced to the market, however when some patients weren’t benefitting as expected, clinicians turned to surgery once more. And with the advent of a strong Parkinson’s animal model a better understanding of the structures involved came about. Surgery and eventually DBS in the mid 90’s became a valid therapy. When the conversation shifts towards DBS for psychiatric disorders, there is a tone of inevitability with trepidation.

“About 4 years ago, I was at a neurosurgical meeting and I heard one of the keynote speakers at that meeting get up and say ‘in the next ten years the largest growth area in neurosurgery is going to be neuromodulatory therapies’. They’re already thinking like that in neurosurgery. Now, one of the problems with all of these neuromodulation therapies is that people go into it without a theory behind the mechanism of action. We kind of did that with DBS, to a point. We thought it was causing a lesion, but now we know it’s not doing that.”

“The psychiatric therapies – people thought a stimulator would solve all of the problems. And now they’re realizing what psychiatrists have known for years, is that depression in one person is not depression in another person. Once again, it comes to tailoring therapies, I think. We’re also learning that different parts of the brain maybe not function appropriately in different disorders.” Despite the inter-individual variability of the brain, and the etiology or severity of psychiatric disorders, does Jay think it will work? “I do. I’ve seen anecdotal results at meetings that it does help some people and it doesn’t seem to be a placebo effect. I think the trials have set endpoints that are just impossible to meet in some cases. Once again, it’s not going to be one therapy for everybody, but if you pick the right patients – like it was in movement disorders – .you’re looking at modifying what I see as substance of the human mind.”

“There’s a lot of ethical questions related to that, but we’re going into those areas now; DBS for resistant vegetative state – that’s an area that’s gotten some research as. So these ethical questions are going to have to be looked at for some of these therapies but I think if they’re done appropriately we’re going to be able to help a lot more people with these techniques, especially as the technology gets better: the right waveforms, the right types of stimulation, patterns, ways to stimulate the patient…things like that.”

Indeed, the idea of using such devices in healthy patients perhaps for cognitive gain is fraught with ethical concerns. There has been an influx of literature in the last decade exploring nootropic drugs to enhance or improve cognition, or transcranial direct current or magnetic stimulation devices for memory retention, which may be considered a precursor to concepts of more invasive ‘neuro- enhancement’.

“I think it’s inevitable. Do I think it’s right? I don’t know. I’ve not come up with a definitive statement in my mind as to whether that is correct or not…it’s like plastic surgery for the brain. If it makes somebody feel better in the long-run, is it a bad thing? Probably not…just at what cost? Fixing a blemish on the skin is one thing, permanently affecting a system we know a lot less about is another”

Similarly, brain-machine and brain-computer interface companies are rapidly on the rise around the world. Some are anticipating that it might supersede the recent influx of medical robotics by forging opportunities for humans to interact with computers and machines. This is particularly promising for treatment solutions for those that suffer from physical or mental degenerative disorders, provided the fusion with artificial intelligence does not compromise the very nature of being human.

Existential concerns aside, Jay is cognizant of the industrialization of intraoperative neurophysiology. Traditionally intraoperative neurophysiology is often provided by (i) in-house hospital personnel, or (ii) outsourced companies. In the U.S., there are an estimated 50+ companies offering neurophysiological testing in surgery, most of which offer benefit to the patient and surgeon, but there have also been a small number of highly publicized (and scrutinized) ‘kickback’ schemes to secure business and increase profits. Australia has not experienced such a high-volume of competitors, however there are early warning-signs that the commoditization of intraoperative neurophysiology might send us down the same path. There are pros and cons to each offering.

“I ‘grew up’ really in an academic institution. If you were to talk to me 20 years ago, my perception of a service-company versus an in-house program would be very different to today. And that’s because I’ve really gone out and talked to people in both areas. I had this ‘sitting on a high-horse’ mindset that academic is the only way to go, all other ways don’t work. But then I got into and got involved and got to see outside service companies in action, and there are some very, very good outside service companies out there. They are as good as any in-house program out there. The problem is, and I think in everything, (are) the bad apples. And there are some really bad apples out there. That’s where the problem is…I think that there are some people who don’t fully understand what it’s like at a hospital that maybe can’t afford in-house monitoring. They don’t understand some of the realities of the situation: how do we offer quality healthcare to every single citizen?”

As INSA takes formative steps to establish regulation of intraoperative neurophysiology in Asia Pacific regions, I asked Jay what he’s observed at the helm of both the ISIN and the ASNM, which he considers the highlight of his career. “Early on, different groups of physicians and societies started working independently, and that caused fragmentation that is still present today…we wasted over 20 years”. With regards to the leadership qualities necessary to facilitate meaningful change; “you are going to offend some people – it is just part of the job. Choose a plan and stick with it”.

Jay is no stranger to diplomacy however he is quick to challenge unnecessary bureaucracy. “Go in with data. If you go in and ask a question, be prepared to support that question, and why you want that resolution you want. Just going in and asking the question I found that people, administrators and other, they have a solution – which is the minimal effort and cost solution. If you come in with your own solution, more than likely they’re going to meet you somewhere in the middle”.

‘Knowledge is power’ in the field of intraoperative neurophysiology, especially given the global disparity in clinical standards, education and training, and accreditation. It’s obvious Jay has built a career using the quest for knowledge and understanding as a means for inspiration. His interest in science as a young’un turned him towards electrical engineering, where he ended up with a doctorate in clinical neuroscience, and eventually taking the helm politically as an advocate for best practice. He might not be considered a rock star in the conventional sense, but those who have observed him lecture on the modulation of the human nervous system would likely recognize a similar degree of assurance in his ‘act’.

Ultimately, he cites perseverance as a key-factor those trying to establish themselves in a field such as clinical neuroscience. “Pick something, and try to stick to it. Early on in your career, you may want to try and should try different things. But there comes a point where you need to focus on something. You should use those early years to figure out what you like. If you keep bouncing from point to point throughout your career, I don’t think it’s going to be as fruitful.”

Indeed, Jay’s perseverance has proven to be fruitful. Not unlike an apple farm.

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