Neuroscience in Motion: Exploring Vision Cognition and Brain-Boosting Power of Exercise for Parkinson's

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Daniel Simon, MD: Hello everyone, this is your Science@UH host Dr. Dan Simon. Today I'm here with our guest, Dr. Aasef Shaikh, Director of Research and Education Center, the Neurologic Institute and Vice Chair of Research for the Department of Neurology and the Penny and Steve Weinberg Chair in Brain Health at University Hospitals. He is also a Professor of Neurology at Case Western Reserve University School of Medicine.

Welcome, Aasef.

Aasef Shaikh, MD, PhD: Thank you, Dr. Simon. It's an honor and a pleasure to be here.

Daniel Simon, MD: Well, before we get into your research, can you tell us a little bit more about your journey into neurology and neurosciences? How did you get interested in the brain?

Aasef Shaikh, MD, PhD: Certainly, my interest in neuroscience, and particularly neurotology - that's how it started. It came from my parents — my both parents are practicing ENT surgeons, and as a child I always saw them talking about ear and talking about how balance system works and auditory system works. So, when I went to medical school, I had this special affinity about hearing and balance system. So, after finishing medical school I wanted to learn more about it, dive deeper into it, so I moved to the United States for higher studies and joined Ph. Ad my lab was based out of the ENT department at Wayne State. And there I learned basic neurotology, auditory brainstem, and tinnitus - that was what my PhD was based on - but as I was doing my PhD, I also had a very keen interest in the vestibular system and the balance system, and in fact, I had this idea of a vestibular prosthesis, which we ended up filing a provisional patent for through Wayne State University. And then after PhD, I pursued my interest into the central vestibular system, for which I moved to Washington University in St. Louis, working with one of the giants in our field, Dora Angelaki.

She was a biomedical engineer and electrical engineer from the background, but Dora told me very early on that my brain is actually wired for a neurologist, and she recommended that I see and work with - as a second postdoc I work with a guy called David Zee. He is one of the very well-known vestibular neurotology neurologists at Hopkins. So, I moved to Hopkins and there everything changed. So, David Zee actually rooted the features of neurologist in my brain and coincidentally, his partner was John Lee, who was a very well-known neurologist practicing out of University Hospitals. So, we had many collaborative projects with John Lee and David Zee, and when I was looking for residency, John Lee said, “Why don't you come here, and you will get to do everything that you're working with Zee?”

So, I thought, ah. How about this? This is a really good idea and I can work with Lee and Zee, both of them and I train with both of them and that would be best of all worlds. That's how I moved to UH to do a residency in neurology.

So, after residency, everybody does fellowship, right? So, I had to do a fellowship, and I was talking to my mentors, and they said that I have to go work with one of their friends, Mahlon DeLong, who was a Lasker and Breakthrough Awardee. And so, I went from Case and UH —I moved to Emory, and I started learning deep brain stimulation and Parkinson’s with Mahlon. And after that John Lee was winding up, he was retiring, he said, “Why don't you now come back after your fellowship and join our laboratory?” And at that time, Doctor Anthony Furlan was the chairman and he recruited me on faculty. That's how everything started in neurotology and movement disorders and combining neurotology with basic neurosciences.

Daniel Simon, MD: It's a great story and it's—it's a story that we all tell, which is: we need amazing teachers and mentors, they guide us down a path and then obviously they take such great honor in your career. So, congratulations.

So, let's shift gears for a moment. You're in the third PI of one of the most famous neurology labs, the Daroff-Dell'Osso lab. Dr. Daroff, who just passed away, was really a legend, a founder of the field of neuro-ophthalmology. What's it like to follow these legends and build on the focus of this lab going forward for you—what’s that been like?

Aasef Shaikh, MD, PhD: It's an amazing and rewarding experience. It's such an honor and it's a very good lab to be part of, and we are very proud of being in this lab. Let me tell you a bit about how everything started and how the team of the lab evolved over decades because the lab was installed in 1970’s when Dr. Daroff moved to University Hospitals as the first chairman of the then newly formed Department of Neurology. And he brought a very bright engineer with him at that time from Miami—that’s where he came from—and his name was Louis Dell’Osso. So Dell’Osso and Daroff came up with this idea of introducing the concept of engineering into neuro-ophthalmology and that was the theme of our lab. And that theme was practiced ever since and has been practiced ever since. This is kind of the backbone of our lab.

So, initial work in the lab was all about nystagmus. A lot of work was done actually on a very common condition called congenital nystagmus, and Bob Daroff was one of the pioneers in describing even acquired forms of nystagmus with engineering concepts, and with oculography. He recruited John Lee in 1980’s. So, when John moved to Cleveland, he brought along the ideas of bringing a bit of neurology into hardcore neuro-ophthalmology. And that's when things started evolving a little beyond pure neuro-ophthalmology.

And John's grants, NIH and the VA Merit Review grants, were kind of incrementally moving from one subspecialty of neurology to the other but looking at eye movement all along for everything. So, he started off with multiple sclerosis and myasthenia gravis. And his last R01 was on progressive supranuclear palsy, which is a form of atypical parkinsonism.

John established some of the best and one of the only pieces of equipment in the world. One of the very unique equipment, which our lab is well known for is called Hexapod, it’s Moog. It's a six-degree-of-freedom motion simulator. It's just like a flight simulator. And John did some initial experiments in that flight simulator with progressive supranuclear palsy, figuring out why they fall so much.

So, all that infrastructure was already in the lab when I first started the lab. But when I joined the lab, I was in a very strategically favorable position. So here I was, someone who was already trained by John Lee and David Z in doing eye movements and vestibular function, having had experience in non-human primates from my work in Washington University. And then I did neurology, and then I did movement disorder with deep brain stimulation.

I had a very interesting experience once when I was a fellow, and that experience actually changed my career and the way I think about the science or that led to my first grant. And I must share that experience. So, one day with Mahlon DeLong, we were in the OR. We were implanting someone with subthalamic nucleus deep brain stimulator. And as part of the procedure, patient is awake, and you put a single unit electrode in the brain, you record from the cell activity, map the right area—then where you want to implant—you stimulate that area and you ask patients what happens subjectively, and then you do the neurological exam to see if things are improved. This is standard.

So, we stimulated one part of STN, and patient said that, “Oh, I am feeling intense sensation of spinning,” which was very odd. So, I looked at Mahlon, who was of course the expert in the field, and Mahlon said, “I don't know.” So, we skipped thinking on that particular instant. Then we implanted the electrode successfully and then patient came to the clinic, and every time we stimulate one part of the brain—one part of STN—he always feels spinning. And then we started paying very particular attention to that part of the brain in several other patients. And it was quite reproducible.

So, we modeled it, and we found that there is a cerebellar thalamic fiber, and in monkeys we know that—based on my studies at WashU—that if you stimulate that you can provoke perception of vestibular sense. So, that was the thing that actually I thought I should start that as a launching pad in the lab.

So, my first grant was looking at how I can modulate the vestibular system in people with Parkinson's. And that grant was very well received because it was so unique. This was somebody who is trained in DBS and movement disorder, eye movement and vestibular system and collaborating with people at biomedical engineering—which is 13th best in the world right now—people from biomedical engineering., and we put together this grant and it received really good score. And one of my career awards, which was given by American Academy of Neurology, they pick one neurologist from the entire country for that, and it was a half-million-dollar grant, and that was my first career grant given to study that.

So, that's how things started. And then you know, it has ripples effect. So, then we started looking at, oh, what happens to the eye movements in Parkinson patients? Because a lot of times when these patients come to our clinic, they tell us that, “I feel blurred, I see double, I cannot see the depth.” So, we asked like what happens to the depth perception, what happens to the perception of reading when they look around?

So, what we found in another federally funded grant—what we discovered was that if you stimulate dorsal part of the subthalamic nucleus, you can actually improve double vision in Parkinson's. So, two-thirds of these people have strabismus and one-third of them have symptomatic strabismus, and that we can improve with stimulation. Not just that, then we moved forward and looked at the visual cognition and visual executive behavior, like when we ask them to look for something and search for something in their environment, they have abnormal executive function. And when we stimulate different parts of the subthalamic region, we can actually improve that. So, it keeps on having this ripple effect and things started moving more from hardcore neuro-ophthalmology to more neuromodulation, and now we are also expanding more into neuropsychiatry.

Daniel Simon, MD: That is an amazing, amazing story. And I think it's a good lesson for our junior career people who are listening and just starting off, that if you observe something unusual, pay attention to it because it led to a whole new career path for you.

Well, let's shift gears for a second. You now have a major research program in exercise physiology. In fact, you scored a top one percentile on a recent grant in that space. Tell us a little bit about Parkinson's disease, exercise and what you're doing to improve quality of life for patients with Parkinson's?

Aasef Shaikh, MD, PhD: Yes, indeed, it was very different, and I never thought that I would be working in exercise physiology as well, as a parallel to everything else that we do in the lab.

So, what happened was, we know as clinicians, we know that exercise is good for brain health in general. And we tell our patients to do mental exercise for cognition or physical exercise for motor symptoms and cognition. And we tell people to do aerobic exercise, right? That is something that we tell people all the time. And there are some studies here and there where people looked at objectively what happens when you do the exercise, but we really don't know exact mechanistic underpinning of how this works and how we can optimize the exercise to make their Parkinson’s or any neurodegenerative symptoms better.

So what happened is—before pandemic—one of my colleagues, Ken LoParo, he was a former chair of electrical engineering at Case, and his colleague Angela Ridgel, who is Associate Director of Brain Health Institute at Kent State, they reached out to me asking if I would collaborate with them on their smart bike project, which is in need of some Parkinson patients.

So of course, my neuroscientist curiosity came up and I said, “This is very interesting and what is smart bike?” So smart bike is their proprietary bike where what happens is patients bike on that smart bike—it's just like a Peloton—but the bike learns how patients do based on the clinical outcomes the patients had, and then they change the bike the next time patient rides. So, bike adaptively is supposed to change. But that requires someone to examine them every time they bike and change the bike accordingly. So, that was a smart bike and they wanted me to be—as a neurologist—to examine the patient every time they bike and then change the bike or give recommendations to change the bike to improve patient’s motor symptoms.

So, we wrote our first grant. Of course, as always, first grant never gets funded, right? So, it never got funded. So, we were working on a revision and then pandemic hit. So, everything came to a standstill. And then these RFAs started coming up about remote healthcare and remote therapy and remote rehab and being friendly to COVID restrictions and things of that sort. So, then we thought like, wait a second—why can’t we make bike remote? Why can’t we have patients bike remotely? Patients can wear wearables, and we have a cloud monitoring the bike, cloud getting the information from the patients, from the wearables like Apple Watch, right?

So, we came up with this concept and we modified the bike a little bit and wrote a grant saying, this is the bike—a smart bike, this is the patient. The patient is wearing a wearable and biking, and then cloud is monitoring the both—and cloud would have an AI algorithm which would change the bike so you won’t need a therapist or a neurologist to change the algorithm. That grant received 1%. So that is now in progress. So, now we are working with this smart bike, which is currently remotely located, but we are training the bike. We are training the algorithm. So, my PhD student still works with the patients, but the idea is to create this AI algorithm which is friendly for the bike and prepare it just like a super version of Peloton, right? Like some adaptive Peloton just for Parkinson’s—but a smart Peloton.

Daniel Simon, MD: It’s an amazing story, and we’ve heard about this from a number of our podcast people that we’ve had —the pandemic—you had to make lemonade out of lemons - things changed and you adapted. And congratulations to you and your team because you went from unfunded to the highest score you can get by adapting the technology for the time. Well, in our last question—this has been so interesting—what’s your vision for research in the Neurological Institute at UH? What’s next?

Aasef Shaikh, MD, PhD: So, there are two projects which are very near and very dear to my heart. One project is to help other junior faculty in my department. So, as many other departments at University Hospitals, we have all these very bright early-career faculty who really want to take the clinical and they want to bring it into the translational world and make a super academic career out of it. And on the other hand, I also work with a lot of basic scientists in biomedical engineering, neuroscience, and fundamental sciences at Case Western, and they are all looking for their clinical partners.

So, my goal is to create some sort of a launching pad for our very bright junior faculty and create a collaboration with other experts who are basic scientists, who are engineers, and come up with novel interdisciplinary ideas. I think this was the secret sauce for my success in science, like multidisciplinary collaboration, and I want to help my faculty—who are junior faculty—to replicate the same career trajectory.

So, I have put together a little task force called a little special interest group in our department, where we meet once a month and we discuss ideas and we mentor them, and we do that for the whole Neurological Institute-wide. So that is one dream that I have to help junior faculty and to build them along the same career path.

The second dream that I had is starting to come true. So very interestingly, every time when we write our career development award there's always a question, “where do you see yourself in 10 to 15 years from now,” in a personal statement, right? So, thinking back in 2016, when I was writing my career development grant, I wrote that one day I want to start a Neuroscience Center for Excellence in my institute, and I want to lead that center and build that center. That dream was always there. Thanks to Dr. Simon—to yourself—and our colleagues at NEOMED, it's already coming true. So, we have this neurodegenerative research center, which is our collaborative effort between University Hospitals and NEOMED. It is already starting to shape, and we are already making good progress in that center. And my dream is to expand that center further to bring more faculty to UH to join our center and bring extramural program grants to fuel that center further.

Daniel Simon, MD: I think our listeners get the sense how lucky a junior faculty would be to have you running a mentoring program for launching a career. It's full payback—you had great mentors who helped you, and now you're gonna help and really define the careers of some junior folks. We're so lucky to have you. I want to thank you for joining us today.

To learn more about research at University Hospitals, please visit UHHospitals.org/UHResearch.

Thank you, Aasef, so much for your time.