Presidential Lecture Awardee: A career observing the brain in action | Congress 2025

And this year's recipient of the prestigious David Marsden Presidential Lecture Award. Please welcome Dr. Jon Stoessel. Jon, thank you so much for joining us.

Dr. Jon Stoessl: Thank you very much for having me. I'm really honored to be here.

Dr. Michele Matarazzo: So to start, I'd like to remind the audience what makes this award quite special. The David Marsden lecture is one of the society's greatest honor is given to leaders who have made extraordinary contribution to the field of movement disorders. Just think of some of the name on that list, Mark Hallett, Jose [00:01:00] Obeso, Alim Benabid, Niall Quinn. And many more like last year lecturer Virginia Lee. Now Jon, congratulations on joining such an exceptional group. What does it mean to you personally to be part of this tradition and what does it feel for you to have this award that is named after David Marsden, which is one of the true founders of our field, of the movement disorders field.

Dr. Jon Stoessl: Thank you. And so people often talk rather loosely about feeling honored and humbled, but in this case, I have to say I am profoundly honored and profoundly humbled, not only because of the memory of David Marsden, but also as you've already pointed out the very illustrious people who have preceded me and I don't feel that I deserve to be in their company.

Marsden of course, was a very special figure in our field. I did not work with him directly, but I did have the privilege of [00:02:00] interacting with him on a few occasions, and he was a remarkable role model as a clinician scientist. And I should say really an outstanding clinician, not only in movement disorders, but I was struck by how much neurology he knew, and of course, his exceptionally inquisitive mind and his endless capacity for work.

Dr. Michele Matarazzo: Yeah. Well, let me not agree with you that you don't deserve to be on that list. But let's go on with with the interview. So at the upcoming International Congress, you'll be speaking on plasticity and compensation in Parkinson's disease. Could you share with us the central themes of the lecture and the messages that you hope the audience will take away?

Dr. Jon Stoessl: We've had an interest for several years in compensatory changes that may occur as detected by functional neuroimaging, molecular imaging in particular. But, this year I would like to [00:03:00] focus on some recent work we've been doing where we're looking at functional anatomical segregation of dopamine release within the basal ganglia.

So we typically think of somatotopic organization in the striatum and also functional segregation according to motor associative and limbic loops. But interestingly, there's been rather little done looking at whether this segregation is respected in Parkinson's disease. And so we've been doing studies in which we attempt to elicit dopamine release that should be either anatomically discreet by looking at different body parts or separating the different functions, motor versus non-motor functions. And whereas we do see a degree of segregation in healthy controls. This is lost in Parkinson's, and [00:04:00] so we're still in the midst of doing these studies to better understand the implications and whether or not these changes could be reversible.

Dr. Michele Matarazzo: That sounds incredibly interesting. And this is just the last part of a story of looking at the brain through neuroimaging and PET imaging, and you've been at the forefront of using neuroimaging to unravel the mechanisms underlying Parkinson's disease and also other related disorders.

What I wanted to ask is when you first started applying neuroimaging to study the living brain. How did it feel to have this window to the living brain to see what is happening in vivo and how do you think it changed the way of thinking as a clinician and also as a researcher, and how did those experience influence the direction of your work?

Dr. Jon Stoessl: I still think of the brain as something like a magnificent cathedral. And so one walks inside and is [00:05:00] overwhelmed by the incredible beauty and architecture. And while most of us spend our lives trying to better understand the brain. At the end of the day, we don't want to ever totally understand it because we still want this sense of mystery, I think.

And so that's how the imaging feels is it opens up a new window. I was very lucky. I started my fellowship after residency in Vancouver, and it was at a time when PET was just emerging. Actually, interestingly enough, we did some early work looking at functional connectivity, using glucose metabolism in patients with dystonia and found all evidence for altered connectivity, albeit using, in retrospect rather crude approaches that nobody would accept now. And then of course over the years you can document [00:06:00] things like dopamine deficiency, but we've had the good fortune. I've been fortunate to work with a lot of people who are much brighter than I am to look at how different markers of dopaminergic function change and also at some of the behavioral correlates of dopamine release in the brain.

Dr. Michele Matarazzo: Yeah, and building on that over the years, your research has helped built a detailed picture of what is happening in the Parkinson's disease brain. And you were mentioning just some of these things like looking at dopamine from different angles, but not just dopamine, then serotonin, acetylcholine, metabolism and proteins.

So many different ways. And many different pieces of the puzzle that is the brain and that are those neurogenerative diseases. So you really helped a understanding what is happening in the brain of people having these diseases. But one important thing is that all of this information [00:07:00] sometimes can be overwhelming and especially put all of this information in line to understand what happens first and what happens next.

And then all the concept of compensation that you were talking about, I think for all of this one thing that you have showed us that you're really able to do is to interpret biologically what the results of the neuroimaging gives us. And I wanted to ask you how do you navigate the complexity of all of this and, specifically, I also wanted to ask you, and I think that's a good message also for the younger people who are interested in this. If there's been any time when the data was completely different to what you were expecting.

Dr. Jon Stoessl: I would say the majority of the time. That's actually an important message, I think because while it's important to have a hypothesis, I think before one starts the work. At the same time, one wants to approach it with an open mind. And yes, sure, I can give you a number of [00:08:00] examples.

Probably, ironically, the work that I will be best known for is our work on dopamine release in response to placebo. And this was really an accident, I have to say. We were doing the study for a completely different reason. Some of the results didn't line lineup as expected, and it was as I think, Raúl de la Fuente-Fernández, who spent a long time thinking about it, we talked about it at great length, and then he realized that the difference in baseline results had to do with whether people were studied in open baseline or after a saline injection. And of course, as soon as he pointed that out to me, I understood the significance of this.

I also, was afraid that people wouldn't be able to reproduce it. But eventually, I think this is fairly well established now. Raul spent a lot of time and was very [00:09:00] good at looking at alternate interpretations of findings that didn't make sense. The other time is a story that's very well known to you.

We did some studies looking at other neurotransmitter systems in people with genetic variants that are deemed pathogenic, in the hopes that we could somehow prove the Braak hypothesis by demonstrating decline in other transmitter systems prior to evidence of dopamine deficiency.

And, what we found was the exact opposite. And initially, when the data were brought to me, I said do it again. Get it right. And then it was very clear that we were actually seeing increases. We still don't fully understand what those increases mean, but I think it really does point to the importance of listening to the data and then being able to [00:10:00] bounce ideas off of other people so that you have a discussion amongst your colleagues and think about what potential explanations could be.

Dr. Michele Matarazzo: And that's one of the fun part of doing research, right? It's when you have to speculate what happens and also then go back to the literature to find evidence to support any other idea that might fit with your unexpected data.

That's

Dr. Jon Stoessl: Yeah, and I think it really highlights, particularly in my career, the importance of transdisciplinarity. My closest colleagues over the years have included nuclear chemists and physicists who bring obviously a very different skillset without which we couldn't do the studies, but also different perspectives, and as they become closer they essentially become neurobiologists over the course of their careers because of our discussions.

Unfortunately, I have not yet picked up the [00:11:00] skillset to become either a chemist or a physicist, but I'm working on it.

Dr. Michele Matarazzo: And you also highlight the concept of plasticity. Can you explain just in few words what do you mean by plasticity and what does it mean in the context of Parkinson's disease and how do you use PET imaging. 

Dr. Jon Stoessl: So we know that there is functional rewiring at any rate. In our case, we predominantly look at it in terms of neurotransmitter release. One example in that case would be the, we found that intensive exercise could increase dopamine release in the basal ganglia elicited by corticostriatal stimulation using TMS.

But of course, other people have done work in this area looking at functional connectivity with MRI, Rick Helmich, in particular comes to mind. Looking at functional connectivity in people who have pathogenic variants, [00:12:00] again, so demonstrating changes in the patterns of connectivity prior to the onset of disease.

And what does this mean? Is it compensation? Presumably some of it is, but the other side of this is that if you compensate by engaging circuitry that is normally reserved for something else. Then when you try to do two things together, that may all fall apart.

So plasticity and compensation are not always necessarily a good thing, but the fact that they may be amenable to interventions such as exercise is a very promising aspect.

Dr. Michele Matarazzo: Great. Now I'd like to turn to your professional journey and talk a little about early days and the road ahead, not just your early days and your road ahead, but in the field in general, and also some of the key lessons that you've learned along the [00:13:00] way. So thinking back to when you started your career, how would you describe the main ways the field of movement disorders and specifically neuroimaging in movement disorders has changed over the years, and what do you see as the most exciting direction of the decade ahead?

Both in general, and how do you think you will contribute to this?

Dr. Jon Stoessl: Well, I've been thinking about this quite a bit actually, because if I go back even before my entry into movement disorders. One of the things that a key influence on my deciding to have a career in neurology was as an undergraduate student when I had a reading course. And of course this is long before the days of the internet and we would have to physically go to the library and pull out the readings and what I remember is reading a paper of Wilder Penfield's on recording the stream of consciousness. I vividly remember sitting in the library feeling spellbound by this [00:14:00] concept that he could put on an electrode on the brain of somebody with epilepsy and evoke an extremely vivid memory. And that was probably the moment when I decided I had to do neurology.

Imaging has of course changed a lot since I started. In the earlier days people were still using imaging as a form of either metabolic phenology, if you will. So increased or decreased glucose metabolism and also in a descriptive fashion to demonstrate a deficiency that we already knew was there.

So I think the exciting changes have been in, conceptually probably the most important change has been what is now routinely recognized as the importance of changes in connectivity. That people had not adequately considered in the past. Also [00:15:00] in terms of molecular imaging, the in creasing capacity to study different targets.

And so we're not quite there yet, but we're at a stage where we can look at protein pathology with molecular tools. And then the growth of MRI, which also started as an extremely descriptive tool, but has now actually in many ways supplanted molecular imaging in terms of its capacity from both the diagnostic perspective, but also to look at altered plasticity. 

Dr. Michele Matarazzo: Great. Now for the next question I know that you're a humble person, so maybe you won't like that but you have certainly inspired many clinicians and scientists in our community. So, that is a fact. And I would like you to tell these people, what guidance would you offer to those who are just beginning their journey in movement disorders, [00:16:00] both as a researcher and as clinicians.

Dr. Jon Stoessl: A couple of things. What perhaps the most important of all is to follow your heart. Do what you love and not what you think other people want you to, because today's hot area will become at some point passe. And if there's something about which you feel passionate, it's really important that you follow that.

Another important thing is in fact, related to humility. Which is that we're blessed to be part of a large family. The Movement Disorder Society has some 12,000 members some of whom are very prominent and well known. At earlier stages in my career, I would never have dreamt to approach these people because they were important and I wasn't.

But the fact is, we are very lucky that we have people who, these people actually are not [00:17:00] only willing to help, they're keen to do so, and one of the great joys of my career has been the network of great friends and colleagues. And you know, when you have a problem or something you want to discuss there's always somebody on the end of a phone or email that you can reach out to.

And then the last thing, maybe more advice to mentors than to trainees, but I guess it's a bit of both, is question everything. Despite the advances in the field, it's still full of dogma and people tend to latch onto certain concepts. And while some of them may be true, I think it's much more important to view them with a critical mind and to really ask yourself, how strong is this evidence?

And how could I work to disprove it?

Dr. Michele Matarazzo: Well, thank you for those advices. Now looking back on your [00:18:00] career so far, what do you hope will stand out as your lasting contribution to the field?

Dr. Jon Stoessl: I think that's always a matter of luck. Obviously the work on placebo effect has had some impact. I think our work on compensatory changes on changes associated with disease progression and on mechanisms of complications of therapy. I think these all play a part in changing the way we think about a problem.

And that's really, at the end of the day, what you want to do. But I would hope that my other legacy would in fact be to have encouraged younger, brighter minds to question not only what they hear from others, but what they hear from me. Because I think it's that ability to contest a prevailing thought that is the most important thing to develop.

And I have to say, when I look at my own career of the people who [00:19:00] I've been exposed to. What you will remember about people is not how many publications they had or what their h-index was, it's how kind they have been and how supportive they have been to others more junior.

Dr. Michele Matarazzo: And I think you have a lot of things to contribute to, but so far you have already accomplished all these things you were mentioning. Now we are getting to the end of this interview, Jon, thank you so much for sharing your reflections and giving us a glimpse of what you're going to talk about in your upcoming lecture.

It's been a very fascinating discussion, and I know that listeners will take a lot from it both scientifically and also personally as personal guidance. Is there anything else that you want to share with our listeners?

Dr. Jon Stoessl: No. Thank you very much again for having me. I think, the great joy that I've had in my career has been from interacting with younger inquisitive [00:20:00] minds.

Dr. Michele Matarazzo: Thank you. And finally a reminder to our audience, Dr. Jon Stoessl, will deliver the David Martin Presidential Lecture at the upcoming Movement Disorder Congress in Honolulu, Hawaii on October 6th, 2025. Be sure not to miss it. It'll surely be a memorable session. Thanks as always for listening.

Dr. Jon Stoessl: Michele, thank you very much.