#36: Béchir Jarraya & Jordy Tasserie – Unlocking Consciousness: Neuromodulation, Neurofeedback, and the Future of Brain Science

Mallory Hacker is an Assistant Professor for Neurology in the team of David Charles, who is Professor of Neurology, Vice-Chair for Business Development and Strategy, as well as the Medical Director for Telehealth at Vanderbilt University Medical Center in Nashville, Tennessee. In 2006, after a stay at Alim Louis Benabids team in Grenoble, France, David started to investigate the question of whether subthalamic DBS could lead to slowing of motor progression in patients with early stages of Parkinson’s Disease. In a one-of-a kind trial, he collected data on the first patients which were published in 2014.In subsequent follow up trials, many of which were first-authored by Mallory Hacker, Class II evidence that supports this hypothesis could be established. It was a great joy to host Mallory in my lab in Berlin in 2022 and we have looked at the effects of lead locations on patients enrolled in the pilot trial. This is what convinced me that there might be something: The few patients that did not progress at all in their motor symptoms after two years were all precisely stimulated at the optimal location within the STN, while the ones that did progress, were more off target. Indeed, these same optimally placed patients had lower stimulation amplitudes and received less medication – but still had a clearly better outcome. Since the original trial, David and Mallory have been hard at work in trying to secure funding for a phase III pivotal trial, and we discuss how difficult this process has been, but also, that there is hope on the horizon, regarding the next steps!

Harith Akram is the consultant neurosurgeon at the National Hospital for Neurology and Neurosurgery (UCLH) and the Unit of Functional Neurosurgery (UCL) at Queen Square. We discuss Dr. Akram's hobbies beyond the lab and OR and delve into his fascinating journey which culminated in him training in the UK, with many stops along the way. Harith shares insights into his illustrious career, highlighting the key mentors who shaped his path, including Drs. Marwan Hariz and Ludvic Zrinzo. With many anecdotes about these influential figures, he reveals the unique lessons each imparted on his training. We then explore Harith's research and clinical work, from the creation of the innovative 'Gilgamesh' to his highly cited STN symptom-specific sweetspots paper. He discusses the practical impacts of his research on surgical practices and his involvement in pivotal projects like the four-lead OCD trial and thalamic segmentations based on tractography. The conversation also touches on underutilized therapies, such as DBS for cluster headaches, and the exciting potential of a new MR sequence he designed (i.e., FAT1). Harith provides his perspective on the future of lesion-based therapies, particularly cingulotomies for OCD and pain. Harith shares his advice for young researchers, reflects on missed opportunities, and engages in rapid-fire questions that reveal his thoughts on the future of neuroscience and academia. Join us for an inspiring and informative episode that showcases Harith's remarkable journey and contributions.

Jens Volkmann is a Professor and the chair of Neurology at University Hospital Würzburg in Germany and one of the key DBS experts in the field. I have intensely collaborated with Jens and his team and he has been a mentor for me since a long time. In fact, in this conversation, Jens reminded me of exactly when we first met, during a summer school in cortona, italy, where I was fortunate enough to listen to fantastic talks by exciting faculty including Jens about the future of Deep Brain Stimulation. Jens has been a pioneer of image guided DBS and has come up with fantastic concepts and models around the mechanism of action of DBS. He has also largely contributed to advancing the fields based on clinical studies and is very broadly informed about the past, present and future of the field in both human and animal work around the technology. I hope you enjoy this conversation as much as I did, and thank you for tuning into Stimulating Brains!

  Phil Starr is a Professor of Neurological Surgery at University of California, San Francisco and a developer of implantable brain devices. At UCSF, he co-directs a multidisciplinary neurology/neurosurgery movement disorders clinic together with Dr. Jill Ostrem. I’ve been a long-time admirer of Phil’s work and in this conversation we blaze through quite a few of his numerous publications. One key breakthrough and invention of Phils work has been to include Ecog recordings – both intraoperatively but also chronically – to investigate brain signals in various states. We talk about the Open Mind Consortium, Mentorship and the cross-pollination between academia and industry. One key highlight of Phils work is a paper which was accepted for publication in Nature Medicine, at the time of recording this just yesterday. In it, the three co-first authors Carina Oehrn, Stephanie Cernera and Lauren Hammer demonstrate the chronic use of a newly identified cortical physiomarker, which is now referred to as the finely tuned gamma activity. I hope you enjoy this conversation as much as I did, and thank you for tuning into Stimulating Brains!

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.