#42: Kullervo Hynynen – A conversation with the inventor of MR-Guided Focused Ultrasound

Dr. Mark Hallett is arguably the person that put transcranial magnetic stimulation (TMS) on the map. Besides that, he is an authority in the field of movement disorders and motor control, with specific focus – spread throughout the years – on Parkinson's Disease, dystonia and functional movement disorders. In our conversation, Dr. Hallett shares anecdotes from the early time of the TMS field, his large number of mentors and even larger number of mentees, how he was able to treat the pianist Leon Fleisher with botolinum toxin, the enigmatic pathomechanism of dystonia, the mysterious cases of the Havanna syndrome, and his work with functional neurological disorders. We include guest questions by none less than Drs. Mark S. George, Mike D. Fox, Christos Ganos, Robert Chen, Joseph Claßen, Shan Siddiqi and Joseph Taylor. Dr. Hallett is an NIH Distinguished Investigator and the Chief of the Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda. He trained at Harvard Medical School, NIH, Massachusetts General Hospital and the Institute of Psychiatry in London. He is past President of the International Federation of Clinical Neurophysiology and the President of the newly founded Functional Neurological Disorder Society. Dr. Hallett is also remote past President of the Movement Disorder Society and past Editor-in-Chief of Clinical Neurophysiology. He has won many awards including, in October 2019, the World Federation of Neurology Medal for Contributions to Neuroscience. His work mainly deals with principles of motor control and the pathophysiology of movement disorders. He authored >1,200 scientific papers with more than 160,000 citations and has an H-index of 212. According to research.com, Dr. Hallett is the 75th most cited researcher in the US, and 104th in the world.

In our ongoing exploration of the DBS ecosystem through the lens of key industry leaders, below is our conversaion with Amaza Reitmeier who is the Vice President and General Manager of Brain Modulation at Medtronic. We learn differences between life in academia and industry, with a key potential of industry work to get the ability to make change at scale. In this episode, we discuss what the future of brain modulation may offer, with some aspirational commentary on several potential opportunities for DBS and related therapies. Some of the opportunities we discuss are currently under development by Medtronic or others, while other opportunities may still be in a nascent state without a concrete roadmap for incorporation into a particular product or therapy.

In this very special episode, we are thrilled to welcome back Ben Stecher, marking his remarkable third appearance on StimBrains (you can find him previously featured on episodes #12 and #14). Today’s discussion takes a profound turn as we delve into the unique collaboration between Ben and his neurologist Dr. Alfanso Fasano, who is a Professor in the Department of Medicine (Division of Neurology) at the University of Toronto. Together, they’ve co-authored ‘Reprogramming The Brain‘, a book that offers a new vision for the future of brain science and neuromodulation. We are very excited to delve into this voyage as seen through the eyes of both a patient navigating the complexities of Parkinson’s disease and his doctor.

When I interviewed Marwan Hariz for episode #4, he wrote in an email: "When you finish the series and all interviews, please let me know because then I should interview you as the Grand Finale of this series…". Throughout the recordings, I heard similar remarks from other guests but also, increasingly, from listeners of the show. After Nico Dosenbach suggested the same in #39, Mike Fox called me and offered to interview me for a round episode of the podcast. With this episode, Stimulating Brains turns #50, and we are indeed flipping the mike so I finally get to experience what I put my guests through on the podcast. Who could have been a better host than Mike for this conversation – as a mentor of tremendous importance, he has been around for (and facilitated) most of the key turning points in my career. Mike and I talk about a lot of things that even covers my youth (thanks to a guest question by Mike Okun), my passion for music, key stages of my career and of course connectomic deep brain stimulation and a thing my lab has begun calling 'the dysfunctome'. We also reflect on the purpose of the podcast and I get to talk at length about how rewarding an experience it has been for me. We then speculate about its future and the future of the field of neuromodulation. Writing this, I want to take the opportunity to thank you all for the continuous support of Stimulating Brains – and of course for tuning into this episode, as well!

Dora Hermes and Kai Miller are associate professors at Mayo Clinic, where they have become a powerhouse on neuroscience, due to their strong collaboration and work in neural signal processing and analysis. Dora has a mathematics background, while Kai studied physics, including a PhD in physics, before becoming a functional neurosurgeon. Last year, both of them last authored a paper each at Nature Neuroscience, each with remarkable and groundbreaking findings about pretty different topics. The first paper dove into the organization of the primary motor cortex using invasive electrophysiological recordings in humans. The second measured conduction delays along fiber tracts in the developing brain.We hope you enjoy this conversation as much as we did!

In our ongoing exploration of the DBS ecosystem throughout the podcast, we've engaged with leading voices in academia, clinical practice, and the patient community, each offering invaluable perspectives on the transformative impact of DBS. Yet, the journey from laboratory to bedside is a collaborative endeavor that requires another critical player: the industry. The symbiosis between innovative scientific research and robust industry support is crucial for the successful transition of groundbreaking therapies from concept to clinical application. Today's feature is with Dr. Binith Cheeran, M.D., Ph.D., who is the Head of Brain Therapies at Abbott. Before joining Abbott, he spent more than 10 years treating patients as a clinical neurologist in Oxford and more than 15 years in academic research, work for which he was honored by the International Parkinson and Movement Disorder Society.

Marwan Hariz and Joachim Krauss need no introduction. First, because they are famous, and second, because they have been on the show, before. In fact, Marwan Hariz is the first to have been on the podcast three times, first, as an early adopter and trustee in episode 3, second, together with Joachim Krauss and Christian Moll in episode 33, and now again with Joachim in the present episode. I met Joachim in Grenoble at a meeting celebrating the 30th year anniversary of STN-DBS. He mentioned that the last episode had been fun, and that it could be great to do an episode on the history of pallidotomies. Needless to say, I would always spend as much time as I can get to speaking with these legends in the field, so of course we went ahead with the idea. I think there are few people that know as much about the history of stereotactic surgery as Joachim and Marwan. In fact, recently, they have been designated as the Historians of the ESSFN and also of the WSSFN (the latter together with Rees Cosgrove). In this conversation, I learned that pallidotomies came in two waves throughout history, and we may be witnessing the beginning of the third wave now with the growing popularity of focused ultrasound surgery. So sit back and enjoy while Marwan and Joachim take us on a ride through the centuries to shed light on the convoluted historical path of the surgical procedure we call pallidotomy.

So far, in the podcast, I have been interviewing key opinion leaders from academia and clinical practice, and sometimes individual patients that graciously shared their insights after undergoing DBS. However, beyond patients and clinicians, there is a third component necessary for DBS to be successful, which are our partners in the industry. Without great industry leadership, it is hard if impossible to translate scientific findings into clinical practice. For instance, when the Grenoble team developed deep brain stimulation back in the 80ies and 90ies, they needed a strong industry partner to bring their breakthrough therapy into clinical practice. In some of the upcoming episodes including the present one, I will interview executives from the device industry. Who better to start this journey with than Todd Langevin, who has been a key figure in the field of DBS and neuromodulation on the industry side. Following the success of Benabid’s team in Grenoble, inside Medtronic, Todd led the internal venturing team that pitched, developed and launched DBS, which is now an $800M business worldwide. So – in a sense – we may owe it to Todd’s team similarly as much as to the scientific and clinical team of investigators in Grenoble that DBS has become a therapy that is being applied, world-wide. During his 20 years at Medtronic, Todd grew the DBS business to a $350 million unit revenue. After a brief hiatus in the cardiac world, he moved back into the field of DBS to lead the startup Functional Neuromodulation as CEO, which aims at establishing DBS to the fornix as a treatment for Alzheimer’s Disease. Indeed, under Todd’s leadership, the company achieved a CE mark for the treatment in Europe. Finally, in 2021, Todd moved to Biotronik, where he currently is the President of the Neuromodulation Business.

In this special episode of Stimulating Brains, we dive deep into the intricacies of the human brain with two esteemed guests, Mac Shine from Sydney University and Paul Cisek from the University of Montreal. Building upon our earlier conversation with Mac in episode 9, this episode sees these brilliant minds sharing their insights on the basal ganglia, the role of dopamine, and the fascinating interplay between various brain regions. In addition, we explore the modulation of the thalamus by the basal ganglia, discussing its impact on both the cortex and the brainstem. Moreover, the conversation takes us on a journey through the evolution of the brain, examining the concept of the phylogenetic refinement approach. Join us in this intellectually stimulating episode as we explore groundbreaking concepts that could significantly impact both systems and clinical neuroscience. 

In this conversation with Jennifer ('Niffy') Thomas and Dr. Michael Stanley, we talk about how Niffy became an artist after undergoing DBS surgery to treat her early onset Parkinson's Disease. Dr. Michael Stanley is a cognitive neurologist at the Brigham & Women's Hospital and has special interest in art and the brain: He studies how lesions or other neurological conditions can lead to cessation of artistic behavior or how they can change the artistic style of artists. When he read about Niffy's case, he reached out to her and the two had multiple conversations about it. In preparation to this conversation, we were in contact with Dr. Paul Krack (Bern) who has studied and published upon similar cases in which DBS surgery changed or initiated artistic behavior. There is so much we can learn from Niffy and I am very grateful for her taking the time to share her story: Indeed, in her youth, Niffy did not enjoy art class at school and never had a particular interest in painting. She expressed herself differently: Via athletic competition or by playing the piano. But after coming home from DBS surgery in 2019, all of a sudden, there was this imminent urge – to paint...