Stimulating Brains

Today we had the privilege of speaking with a true pioneer in the field of neuropsychiatry and brain stimulation— Dr. Harold Sackeim.Dr. Sackeim is perhaps best known for his extensive research on electroconvulsive therapy (ECT), but his contributions span a wide range of topics from treatment-resistant depression to the placebo effect in neurostimulation. As a founding figure in modern ECT research, he has played a central role in shaping both the science and the clinical practice of brain stimulation therapies.In this episode, we explored the history and future of ECT, the controversies surrounding it, and Dr. Sackeim's insights on the direction of neuromodulation. He explains how ECT has long been the most effective treatment for severe, treatment-resistant depression. While once overlooked in favor of medication, we now know that both the placement and intensity of stimulation are key—challenging the old belief that seizures alone drive its effects.

In this episode, we journey through the remarkable career of Dr. Rees Cosgrove—a trailblazer in functional neurosurgery, Director of Epilepsy and Functional Neurosurgery at Brigham and Women's Hospital, and Professor of Neurosurgery at Harvard Medical School.Dr. Cosgrove reflects on his formative years training in the very halls that were roamed by legends such as Wilder Penfield at the Montreal Neurological Institute, and takes us through pivotal chapters of his career leading programs at Massachusetts General Hospital, Brown University, and now the Brigham. With a repertoire that spans from the golden era of ablative neurosurgery to modern deep brain stimulation and MR-guided focused ultrasound—where he has performed over 600 sonications—Dr. Cosgrove provides a unique perspective on how the field has transformed over the past several decades.Throughout the conversation, we delve into the history and resurgence of surgical lesions for psychiatric and neurological conditions, the nuances of neuromodulation technologies, and the evolution of imaging that now defines precision in brain surgery. Dr. Cosgrove also shares his views on mentorship, the transmission of surgical wisdom, and how we can preserve the disappearing art of lesioning in an age increasingly dominated by stimulation.Whether you're a neurosurgeon, neuroscientist, or simply curious about how we interface with the brain to treat disease, this episode is a rare and insightful look into the mind of one of the field's most experienced and thoughtful pioneers.

In this episode we will dive deep into the minds of leading researchers and clinicians in the field of neuromodulation. Today, we are thrilled to have Dr. Terry Sanger with us.Dr. Sanger is a renowned pediatric neurologist, engineer, and Chief Scientific Officer at CHOC, where he focuses on improving the lives of children with movement disorders—especially dystonia. He's well known for combining deep computational approaches with cutting-edge neuromodulation techniques.In this episode, we'll uncover how his background in engineering, neuroscience, and clinical practice converges to shape new possibilities for treating complex movement disorders in children. From pioneering multi-electrode deep brain stimulation for pediatric dystonia to his latest forays in closed-loop stimulation research, Dr. Sanger is truly expanding the boundaries of what's possible in pediatric care.

In this episode, we have the privilege of speaking with Dr. Todd Herrington, a leading neurologist and director of the Deep Brain Stimulation (DBS) program at Massachusetts General Hospital. Dr. Herrington specializes in movement disorders such as Parkinson's disease, tremor, and dystonia, and his research focuses on the motor, cognitive, and psychiatric effects of DBS, leveraging intraoperative and noninvasive neurophysiology and neuroimaging to advance neuromodulation therapies.Today, we'll explore his key role in the ADAPT PD trial, a groundbreaking multicenter study evaluating the safety and efficacy of adaptive DBS for Parkinson's disease. This trial, led by Dr. Helen Brontë-Stewart at Stanford, introduced a neurostimulator capable of sensing local field potentials and dynamically adjusting stimulation in real time based on a patient's brain activity. We'll discuss how this technology represents a shift toward personalized DBS therapy and what it means for the future of neuromodulation.In the second part of our conversation, we'll delve into broader topics, including the mechanism of action of DBS, novel neuromodulation approaches, and the potential role of stem cell therapy in movement disorders. Dr. Herrington shares his expert insights on how these advancements shape both our scientific understanding and the clinical application of DBS. From improving motor and non-motor symptoms in Parkinson's disease to pioneering adaptive neurostimulation, his work is at the forefront of innovation in the field.

In this episode, we're joined by Dr. Jonathan Downar, a psychiatrist and neuroscientist based in Toronto, renowned for his pioneering research in transcranial magnetic stimulation (TMS) for depression. You may recognize him from his landmark work on the Three-D Trial, which helped establish intermittent theta-burst stimulation (iTBS) as a rapid and effective alternative to standard repetitive TMS.Recently, Jonathan has been pushing the boundaries of TMS with accelerated treatment protocols, including the One-D Study, which tested the feasibility of delivering an entire TMS course in a single day.In our conversation, we explore his scientific journey, the future of brain stimulation, and his bold approach to innovation—what he calls “TMS in SpaceX mode.” We also discuss the vision for achieving a billion depression patient remissions in our lifetime.Tune in for an inspiring and insightful discussion with one of the leaders in neuromodulation research.

In this episode, we have a privilege to talk with Dr. Roxanne Lofredi, a prominent researcher investigating movement disorders and deep brain stimulation (DBS). Dr. Lofredi is based at Charité – Universitätsmedizin Berlin and is widely recognized for her groundbreaking contributions to understanding how basal ganglia networks drive motor symptoms in conditions such as dystonia and Parkinson's disease. Today, we'll explore two fascinating studies led by Dr. Lofredi. The first focuses on how subthalamic nucleus stimulation impairs stopping of ongoing movements in Parkinson's disease. This work, published in Brain, was inspired by a foundational basic science study from Aron and Poldrack (2006), which first implicated the subthalamic nucleus as a critical node for motor inhibition within the hyperdirect pathway of the basal ganglia. We'll discuss how these findings translated to her DBS study and how they may impact DBS therapy. The second part of our conversation will cover her recent publication in Nature Communications, where Dr. Lofredi and her team demonstrate a clear link between striato-pallidal oscillatory connectivity and symptom severity in dystonia. This work highlights the pathophysiological role of the direct pathway within the basal ganglia and opens up new possibilities for targeted therapeutic approaches. In conclusion, Dr. Lofredi shares key insights from her research, bridging the gap between basic neuroscience and clinical application. From understanding motor inhibition in Parkinson's disease to exploring striato-pallidal connectivity in dystonia, her work advances our knowledge and paves the way for more effective DBS therapies.

In this episode of Stimulating Brains, we're thrilled to have Jim McNasby join us. Jim is a deep brain stimulation (DBS) patient and the Chief Counsel at the Michael J. Fox Foundation. Jim has an inspiring story, not just as a DBS patient but also as a legal professional working at the forefront of Parkinson's research advocacy. We'll dive into his personal experience with DBS—how it has shaped his life since his diagnosis in 2000 and his surgery in 2019—and explore his crucial role at the Michael J. Fox Foundation, where he helps drive forward their mission to find a cure for Parkinson's disease. I had the pleasure of hearing Jim speak at the Neuromodec Conference, where he shared a powerful story of how DBS transformed his life, even showing a video that vividly captured its positive effects. We'll talk about that, his DBS wishlist, and the work he's doing to advocate for patients and drive research. In this episode, we explore his personal experiences, the impact of DBS, and his role in advancing Parkinson's research and advocacy at the foundation. Jim also reflects on the transformative moment when his DBS was first activated and discusses his vision for the future of patient care and innovation in the field.

Today, we have the pleasure of speaking with Dr. Bálint Várkuti, a distinguished expert in the field of neuromodulation. Dr. Várkuti is the founder and CEO of CereGate, a pioneering company developing brain-computer interface technologies—referred to as computer-brain interface technologies—that aim to enhance neuromodulation therapies. Before founding CereGate, Dr. Várkuti made significant contributions to image-guided DBS programming solutions at Brainlab. With over a decade of experience in neurotechnology and the medical device industry, his work focuses on designing innovative interfaces between technology and the human brain to improve patient outcomes. For those familiar with DBS, you'll understand the nuances here: when stimulation of the super-dynamic nucleus in DBS is set too high, patients often experience a tingling or irritating sensation due to overstimulation of sensory fibers. Typically, this side effect is avoided. However, Dr. Várkuti had a groundbreaking insight: This sensation represented a channel of information with the brain – and one could make use of it! In a nutshell, CereGate leverages these overlooked pathways, using them in a patterned and complex way to transmit information that the brain can decode. This approach opens up new possibilities for interfacing with the brain, which we find truly fascinating: This concept that CereGate is exploring might just be the start of a much larger field of innovation.

In this episode, we have the pleasure of hosting Mark McAuley, a deep brain stimulation (DBS) patient and the CEO of Astronomy Australia Limited, and Dr. Susan Boehnke, an Associate Professor at Queen's University in Canada and director of the Neurotech Microcredential Program and the Neurotech Discovery Lab. Together, they've been part of remarkable efforts that not only focus on the practical and ethical aspects of neurotechnology but also engage students in real-time research. Mark brings over thirty years of experience in research and development, with a remarkable track record of securing $300 million in Australian Government grants for major research infrastructure projects. Holding degrees in astrophysics, ancient history, and an MBA—where he was awarded the Vice-Chancellor's medal as the university's highest-achieving postgraduate student—Mark was diagnosed with Parkinson's disease in 2010 and received a DBS implant in 2020. Post-surgery, he's been a passionate advocate for better patient care and improved DBS programming to enhance clinical outcomes. Dr. Susan Boehnke completed her PhD in Neuroscience at Dalhousie University and has an extensive background in auditory neuroscience and primate neurophysiology. She led the creation of one of the first non-human primate models of Alzheimer's disease and established Canada's first non-human primate biobank. In response to the explosion of interest in neurotechnology, she's now pioneering a micro-credential program in neurotech and exploring the ethical issues surrounding it. She's also leading the Training Committee for Connected Minds, a significant research initiative between York and Queen's Universities. At the recent Neuromodec conference in New York, Mark and Susan presented their work, which emphasizes patient inclusion in research—a theme Dr. Boehnke passionately advocates for—and provides transformative learning experiences for students. Today, we'll dive into their journeys, the science behind their projects, and explore potential insights into the future of patient-led research and education in neurotechnology.

In today's episode, we dive deep into two groundbreaking studies led by Daniela and Clément. We explore their 2022 Nature Communications paper on using cerebellar stimulation to alleviate levodopa-induced dyskinesias in Parkinson's disease and discuss their 2023 paper uncovering the cerebellum's role in regulating fear extinction through its connections with the thalamo-prefrontal cortex pathway. Along the way, we discuss how these discoveries may open up exciting new possibilities for treating both motor and emotional disorders. Tune in for an insightful conversation packed with cutting-edge science and exciting future perspectives!

In this episode, I was able to talk to Dr. Shan Siddiqi, who is an Assistant Professor of Psychiatry at Harvard Medical School and a researcher at the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital, where he and his lab focuses on brain circuit therapeutics. Shan's work bridges the gap between neuroimaging and causality, exploring the mechanisms of brain stimulation and lesions in neuropsychiatric disorders such as depression and post-traumatic stress disorder (PTSD). He's made remarkable strides in understanding the brain circuits involved in these conditions and how we can leverage this knowledge for neuromodulation therapies. Shan has worked on numerous topics that focus at improving transcranial magnetic stimulation (TMS) for psychiatric indications by using brain connectomics. Using various causal sources of information, he was able to show that the same network is associated with changes of depressive symptoms in patients with brain lesions, major depression, epilepsy or Parkinson's disease – and this network could be identified using various types of brain lesions, transcranial magnetic or deep brain stimulation sites. More recently, Shan has worked on identifying a novel TMS target for PTSD based on data from penetrating head trauma lesions and TMS sites. He has worked on conceptual papers that revolve around closing the causality gap in neuroimaging, as well as on how to bring connectomics into clinical practice in psychiatry. His recently launched prospective R01 funded trial will aim at prospectively mapping random cortical stimulation sites to various behavioral and clinical outcomes.

In this episode, we're joined by Dr. Suthana, a leading neuroscientist from UCLA's David Geffen School of Medicine and the Jane & Terry Semel Institute for Neuroscience & Human Behavior. Dr. Suthana's career sits at the intersection of neuroscience, neural technology, and engineering, focusing on memory disorders and innovative brain technologies. We explore her groundbreaking research on memory enhancement through deep brain stimulation (DBS), focusing on a study where stimulation of the entorhinal cortex enhanced memory retention during learning. She also delves into the challenges of translating laboratory findings into real-world clinical improvements. In a truly unique part of her work, Dr. Suthana uses virtual reality (VR) and mobile tech to study memory in naturalistic settings. Her lab even developed a custom backpack system, allowing participants to move freely while recording real-time brain activity to better understand memory and spatial navigation. We also discuss her recent work on PTSD, where she uses responsive stimulation in the amygdala to help reduce trauma-triggered responses. Dr. Suthana expresses her excitement about the future of wearable tech and how it might revolutionize the field by combining real-time data collection with neurostimulation. Tune in for an inspiring look at the future of neuromodulation and memory enhancement as Dr. Suthana shares her vision and insights into this cutting-edge field.

As a fourth installment of this podcast into key industry leaders in neuromodulation, this is our conversation with Milad Girgis, who is the VP and General Manager of the Brain franchise at Boston Scientific. Milad has dedicated over 25 years to the Medical Device Industry, with two decades at Boston Scientific. Before diving into his impressive tenure at Boston Scientific, we explore the earlier phases of his career and identify key turning points that shaped his professional journey. Milad provides insights into what his typical day at Boston Scientific looks like. We also discuss the competitive DBS landscape and how they create unique selling points for their program. Milad shares exciting developments and future plans that are on the roadmap, giving us a glimpse into the innovations driving the industry forward. Finally, we illuminate Boston Scientific's approach to DBS with their unique strategy and focus on image guidance – among other concepts. Our conversation also addresses the academic community's curiosity about transitioning to industry roles, with our guest presenting a compelling case for why a career in the medical device industry can be rewarding. Join us as we explore and map some new potential horizons for neuromodulation.

In this episode, we have an insightful conversation with Dr. Ali Rezai, who is the Associate Dean of Neuroscience at West Virginia University (WVU) and Executive Chair and Director of its Rockefeller Neuroscience Institute (RNI). We take a deeper dive into Dr. Rezai's career, which features his notable achievement of performing 900 neurostimulator implants by 2006. We highlight Dr. Rezai's involvement in deep brain stimulation (DBS) and focused ultrasound (FUS), particularly in treating severe traumatic brain injury and addiction. This episode features interesting findings on the sustained effects of low-intensity FUS in addiction, as well as the possibilities of opening the blood-brain barrier for the treatment of Alzheimer's disease. Dr. Rezai shares more about RNI's core mission and his leadership experiences in various medical societies, namely CNS, NANS, and ASSFN. We also discuss anecdotes from his presentations to various politicians, including President George W. Bush. We cover a lot of ground in this episode, and it truly offers a comprehensive look into Dr. Rezai's remarkable contributions to neuroscience and the broader medical field.

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.

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...

In this conversation with Dr. Vanessa Milanese, we cover the importance of anatomy in neurosurgery and explore her intriguing work in both fields – and how they cross-informed one another. Vanessa is a functional neurosurgeon at A Beneficencia Portuguesa Hospital in São Paulo, Brazil and holds an adjunct assistant professorship of neurosurgery at Mayo Clinic in Jacksonville, Florida. We talk about her stellar work in combining her neurosurgical activity with anatomical work – which involves dissections of the white matter of postmortem brains using the Klingler's method. We will talk about the rare community of neurosurgeons involved in similar activities, world-wide and the big influence Dr. Al Rhoton had on the field and on Vanessa's career. We thoroughly enjoyed this conversation and learned a lot – and we hope you will enjoy it as much as we did! Thank you so much for tuning in! References we talked about in the episode: Holanda, Vanessa M., Michael S. Okun, Erik H. Middlebrooks, Abuzer Gungor, Margaret E. Barry, John Forder, and Kelly D. Foote. 2020. “Postmortem Dissections of Common Targets for Lesion and Deep Brain Stimulation Surgeries.” Neurosurgery 86 (6): 860–72.  https://journals.lww.com/neurosurgery/abstract/2020/06000/postmortem_dissections_of_common_targets_for.14.aspx Holanda, Vanessa Milanesi, Maria Cristina Chavantes, Xingjia Wu, and Juanita J. Anders. 2017. “The Mechanistic Basis for Photobiomodulation Therapy of Neuropathic Pain by near Infrared Laser Light.” Lasers in Surgery and Medicine 49 (5): 516–24.  https://www.thieme-connect.de/products/ejournals/pdf/10.1002/lsm.22628.pdf Middlebrooks, Erik H., Ibrahim S. Tuna, Leonardo Almeida, Sanjeet S. Grewal, Joshua Wong, Michael G. Heckman, Elizabeth R. Lesser, et al. 2018. “Structural Connectivity-Based Segmentation of the Thalamus and Prediction of Tremor Improvement Following Thalamic Deep Brain Stimulation of the Ventral Intermediate Nucleus.” NeuroImage. Clinical 20 (October): 1266–73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308387/ Middlebrooks, Erik H., Sanjeet S. Grewal, and Vanessa M. Holanda. 2019. “Complexities of Connectivity-Based DBS Targeting: Rebirth of the Debate on Thalamic and Subthalamic Treatment of Tremor.” NeuroImage. Clinical. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543122/ Ferreira, Tancredo Alcântara, Jr, Erik H. Middlebrooks, Wen Hung Tzu, Mateus Reghin Neto, and Vanessa Milanesi Holanda. 2020. “Postmortem Dissections of the Papez Circuit and Nonmotor Targets for Functional Neurosurgery.” World Neurosurgery 144 (December): e866–75. https://www.sciencedirect.com/science/article/abs/pii/S1878875020320969?via%3Dihub Additional Resources we talked about: Mayo Functional Neuro Course 2024:  https://ce.mayo.edu/functionalneuro2024 Scaniverse app for 3D brain reconstruction: https://apps.apple.com/br/app/scaniverse-3d-scanner/id1541433223?l=en-GB Rhoton's book: https://shop.lww.com/Rhoton-Cranial-Anatomy-and-Surgical-Approaches/p/9781975226879 Stênio Holanda Filho Q&A book: https://www.dilivros.com.br/livro-neuroanatomia-pratica-e-ilustrada-questoes--e-respostas--3d-9788580531527,h18213.html Deep Brain Stimulation: A case-based approach https://academic.oup.com/book/29505

In this episode, we sit down with Dr. Kullervo Hynynen, a key figure in biomedical ultrasound and image-guided therapeutics. Starting from his academic roots at the University of Aberdeen to his current roles at the Sunnybrook Research Institute and the University of Toronto, Dr. Hynynen has played an instrumental role in advancing medical imaging. He has been at the forefront of investigating the use of focused ultrasound for various medical procedures such as non-invasive surgery, vascular surgery, targeted drug delivery, and gene therapy. Without his groundbreaking contributions, the medical field might not possess the capability to execute MR-guided focused ultrasound surgeries today. For those curious about the specifics of his contributions, the Focused Ultrasound Society has a comprehensive website detailing milestones in the therapy's development, where Dr. Hynynen's name frequently appears. Dr. Hynynen leads an extensive group at Sunnybrook, comprising approximately 50 to 100 members. These professionals span across the vast spectrum of focused ultrasound applications in both animals and humans.

In this intriguing dialogue with Dr. Christelle Baunez, a neurobiologist at Aix-Marseille University, we discuss a mysterious and small structure, the subthalamic nucleus. Christelle is known as the STN woman in France, due to her dedication to study this structure over the years. Christelle is a pioneer in the side effects related to STN stimulation in Parkinson Disease patients. Now, she is working towards understanding how STN stimulation can help people with addiction. We cover, with an historical perspective how STN became an interesting brain stimulation target, their advantages and disadvantages of its stimulation, side effects related, its connectivity and current and future applications. In addition, we discuss some of her recent fully unpublish experiments, like STN stimulation in cocaine addicted macaques and beyond. We also cover Christelle's advocacy for animal research and its important role to push the boundaries of neuroscience. Finally, Christelle shares her passion for photography and how STN should be included in the reward circuit. This conversation was an incredible learning experience for me, and I believe it will be for you too.  Thank you so much for tuning in – for this round episode number 41 of stimulating brains!

In this engaging conversation with Casey Halpern, a functional neurosurgeon at Penn Medicine. Casey is a pioneer in both deep brain stimulation and focused ultrasound and with his lab has recently had some fantastic breakthroughs, especially, but not exclusively in the field of loss-of-control eating in severe obesity. We cover a lot of ground from optogenetics at Stanford, basic science research about the nucleus accumbens and translation of findings into patients, serendipitous discoveries in humans, to stereo-EEG procedures in patients with epilepsy. We discuss what made his recent Nature paper about an appetite mediating circuit in the human hippocampus so special, how he took his findings from 2013 in rodent work – across several stages – into a human clinical trial for eating disorders. We also cover Casey's ongoing trial in DBS for OCD, where he adopts an approach to probe the brain with multiple electrodes to then identify optimal target areas for each individual patient – in line with other current advances of psychiatric neurosurgery. We also talk about MR guided focused ultrasound and the potential future of this treatment option in a tight relationship with DBS. As always, I learned a lot in this conversation and I hope you find it as enjoyable as I did. Thank you so much for tuning in – for this round episode number 40 of stimulating brains!

In this engaging conversation with Dr. Nico Dosenbach, a clinician-scientist at Washington University, we dive into his personal journey from the Black Forest in Germany to his adventures in the US. Nico generously shared insights into his educational and career path, recounting his experiences studying biochemistry in New York City, making the decision to pursue an MD/PhD, and eventually specializing in pediatric neurology. The conversation delved into his early days as a researcher at Washington University in St. Louis, during the pioneering early days of resting-state fMRI. Nico also discussed the significance of data collected as part of the Midnight Scan Club. This work collected hours worth of data from ten individuals using comparably long and repeated fMRI scans and led to most of the seminal work of the Dosenbach lab. As Nico lays out, the reason is intriguing: If one sees an unexpected finding on high quality data, one would not as easily attribute it to noise. More likely, one would follow up and try to understand the finding better – as was done in numerous of Nico's papers. Nico tells us how practical it is to wear a pink cast around ones dominant arm for a while – and why one would want to do such a thing as an fMRI researcher. Finally, we talk to Nico about two of his recent groundbreaking papers which were both published in Nature and how it came about that he challenged a long-standing "truth" in neuroscience: The model of the motor homunculus established by Wilder Penfield.

In this conversation with Espen Dietrichs, we talk about the work of Carl Wilhelm Sem-Jacobsen, who almost certainly applied deep brain stimulation to the subthalamic nucleus chronically over weeks in 1958. Notably, this was ~40 years before the application of subthalamic DBS in Grenoble by the team of Alim Louis Benabid & Pierre Pollak (episode 4) following the pioneering animal work by Hagai Bergman (episode 17) and Abdelhamid Benazzouz who had demonstrated lesioning and DBS to the subthalamic nucleus had dramatic effects on cardinal motor symptoms in Parkinson's. Sem-Jacobsen implanted a series of electrodes into the basal ganglia of the brain of Parkinson's Disease patients starting in 1958, and in some electrodes labeled "near nucl. ruber" demonstrated dramatic effects on both tremor and bradykinesia. Espen Dietrichs spent many years researching this work and according to him, Sem-Jacobsen was "an inventor, not so much a scientist", so little was published. He showed a compelling film at the neurological convention in Oslo 1962, however – which had been lost for a long time. After years of investigation, Prof. Dietrichs could recover the film and a total of 9 boxes of material in a barn owned by the Sem-Jacobsen family in rural Norway. He takes us on this journey of investigation and scientific history, and also shares how Sem-Jacobsen built an ECG device that recorded the activity of Neill Armstrong's heart while taking the first steps on the moon, as well as an EEG device that measured brain activity of jet pilots and divers. We touch on conspiracy theories of "mind control", personal links to the director of the CIA and a hearing committee, that ultimately cleared the name of Carl Sem-Jacobsen long after his death.

In this compelling episode we delve into the inspiring story of Jon Nelson, a remarkable individual who has braved the depths of mental illness and emerged as a beacon of resilience and hope. In a heartfelt conversation with Jon, he shares his lived experience with DBS device as a transformative treatment for mental illness. Against the backdrop of prevailing stigma surrounding mental health, Jon's journey unfolds as he not only navigates the challenges of his condition but also becomes an ardent advocate for change. Through Jon's experiences and storytelling, we hope to provide a perspective on the power of DBS in addressing mental health issues and breaking down societal barriers. Tune in as we explore Jon's commitment to dispelling stigma, his unwavering determination to share his insights, and his profound impact on raising awareness about the potential of DBS in treating mental health disorders. This episode challenges preconceptions, celebrates triumphs, and sheds light on the extraordinary synergy between personal experiences and scientific advancements.

In this episode, we delve into the groundbreaking work of the Neuromodulation Lab at the NeuroSpin center, led by Dr. Béchir Jarraya. The lab's mission is to evaluate brain modulation using pharmacological agents and electrical neurostimulation. Combining functional MRI with new neuromodulation techniques, they train awake macaques, with a unique mock-MRI process, to study consciousness-related domains. Their activities encompass MRI, electrophysiology, and 3-photon imaging to unlock the mysteries of consciousness.

In this episode, we interviewed Dr. Mark Richardson, an expert in functional neurosurgery and the Director of the Brain Modulation Lab at MGH Neurosurgery. He shared insights into his career and the lab's focus on improving surgical treatments for epilepsy, movement disorders, and psychiatric diseases through a systems neuroscience approach. We discussed closed-loop deep brain stimulation in epilepsy, incision-less approaches like FUS and LITT, and the role of different nuclei in generalized epilepsy. We also explored speech and language research, therapeutic applications of DBS, olfaction studies, and patient engagement in research trials. Join us to discover the frontiers of neurosurgery and the groundbreaking work of the Brain Modulation Lab.

We had the privilege of interviewing Dr. Charles Jennings, an accomplished scientist and leader in the field of neuroscience. As the Executive Director of the Program for Interdisciplinary Neuroscience and the Ann Romney Center for Neurologic Disease, Dr. Jennings oversees a vast network of researchers and clinicians who are dedicated to advancing our understanding of the brain and developing new treatments for neurological disorders. Dr. Jennings' work is especially noteworthy for its collaborative approach. As a “connectome” here in Boston, he bridges the gap between different research teams, fostering interdisciplinary dialogue and cooperation. He oversees the “Neurotechnology Studios” which is a prime example of this collaborative approach, providing state-of-the-art equipment and technical support to researchers across a wide range of fields. During this episode, Dr. Jennings shared fascinating insights into his career path and the challenges he has faced along the way. He spoke about the importance of mentorship and the role that his own mentors played in shaping his scientific outlook. He also discussed his experiences as the founding editor-in-chief of Nature Neuroscience and offered his thoughts on what makes a successful journal. In addition, we discussed some of the trends and issues that are currently shaping the field of scientific publishing, including the rise of sub-journals, the impact of open access, and the challenges posed by excessive article processing charges. Dr. Jennings provided a thoughtful and nuanced perspective on these topics, drawing on his extensive experience in the field to offer valuable insights and suggestions for the future.

Join us for an illuminating conversation with Drs. Joachim Krauss, Marwan Hariz, and Christian Moll, as we delve into the history of Stereotactic and Functional Neurosurgery, and the impact of serendipity in driving discovery. In the first part of the episode, we explore the fascinating history of Stereotactic Functional Neurosurgery, discussing the advances in technology and surgical techniques that have led to the current state of the field. We also touch on the challenges and ethical considerations involved in Stereotactic and Functional Neurosurgery, as outlined in Rzesnitzek et al.'s paper “Psychosurgery in the History of Stereotactic Functional Neurosurgery.” In the second part of the episode, we turn our attention to the role of serendipity in scientific discovery, inspired by Hariz et al.'s paper “Serendipity and Observations in Functional Neurosurgery: From James Parkinson's Stroke to Hamani's & Lozano's Flashbacks.” We discuss the power of chance observations and unexpected findings in advancing our understanding of the brain and improving patient outcomes. We also debate the strengths and limitations of the serendipitous approach to discovery, in contrast to more systematic methods of target discovery. Overall, our conversation with Drs. Krauss, Hariz, and Moll sheds light on the rich history and exciting future of Stereotactic and Functional Neurosurgery, and the fascinating interplay between serendipity and scientific discovery.

It was my great pleasure to talk with Philip Mosley, who is one of the most experienced neuropsychiatrists working with DBS and published seminal work on non-motor, neuropsychiatric side-effects of subthalamic DBS in Parkinson's Disease as well as DBS for obsessive compulsive disorder when targeting the bed nucleus of the stria terminalis. Our conversation spans many areas from public health, remarkable individual case examples, the role of caregivers in DBS surgery, whether DBS could alter your personality, to boxing, raising three kids and a fast car. Phil has published certainly among the best network DBS papers on neuropsychiatric adverse events in notable journals, involving a virtual casino paradigm and investigating what differentiated patients that struggled with impulsivity and other side-effects after surgery from the ones that don't. After carrying out one of the few randomized clinical trials on DBS for OCD with the DBS team in Brisbane, Phil realized how critical access to this treatment option will be for some patients, so he has become active in pursuing the goal to broaden access to this treatment in Australia and beyond. After listening to the side of neurosurgeons, neurologists and psychiatrists on this podcast, I believe it is a very insightful change of perspective to hear from a neuropsychiatrist that has treated a large number of patients that underwent DBS – so I hope you enjoy this episode as much as I did the conversation with Phil!

It was my great pleasure to talk with Veerle Visser-Vandewalle, who is the Head of the Department of Stereotactic and Functional Neurosurgery at University Hospital of Cologne. As a unique setup, she chairs the stereotactic department with access to their own operating theaters in which they have carried out a wide variety of surgeries, including DBS for Parkinson's, Tremor, Dystonia, OCD, Alzheimer's Disease and Pain; as well as spinal chord stimulation and even brachytherapy as one of the few centers in Germany. At age 34, Veerle published the first neuropsychiatric DBS case in the Lancet, 1999, operating on a 42-year old man with Gilles de la Tourette's Syndrome and self-injurious behavior. It was a good year for DBS: Soon after Veerle, Bart Nuttin published the first case series of OCD-DBS (also in the Lancet) and in the same year, Joachim Krauss published the first three Dystonia DBS cases (also in the Lancet). We discuss how DBS for Tourette's has evolved since the first case and what are next steps to come. Currently, Veerle focuses on fornix-DBS in Alzheimer's Disease, taking part as a key center in the ADvance II trial and was able to report some interesting insights. Finally, we talk about the crisis of access to DBS in diseases with low numbers, such as OCD (based on her recent Nature Medicine commentary), her being a knight of Leopold the II and the book she wrote for her son's 18th birthday, “Plato & Cola or the secret of your brain”, that unfortunately, so far, he didn't read (we are sure that one day, he will!)

It was my great honor to talk with Suzanne Haber about the importance of anatomy in neurosurgery and neuromodulation as a whole. Among many other topics, we discussed her seminal work on the subthalamic nucleus, the anterior limb of the internal capsule and briefly present work on the zona incerta, also in synopsis with earlier work from Mahlon DeLong (#22) and Anne Young (#23). Crucially, Suzanne is not only an anatomist but one with a particular interest in deep brain stimulation. She leads a Conte center with the NIMH focused on Obsessive Compulsive Disorders and has carried out seminal work about the striatal system. One key area Suzanne has worked on lately was the comparison between noninvasive imaging (diffusion-MRI based tractography) and tract tracing data. Together with Anastasía Yendiki (Martinos Center Boston), she runs the "iron tract challenge", in which tractography methods folk competes to reconstruct tracts from diffusion data as best they can – which are then compared to the ground truth from tracing data. Together with Cameron McIntyre (#10), alongside three other anatomists, Suzanne recently created the basal ganglia pathway atlas which represents a unique dataset to study connectomic deep brain stimulation data.

Mike Fox leads the Center for Brain Circuit Therapeutics at the Brigham & Women's Hospital at Harvard Medical School in Boston. The center is unique in that it houses colleagues from neurosurgery, neurology, psychiatry and neuroradiology under the same roof – with the aim to collaboratively work on novel neuromodulation treatments. It is a great honor to interview Mike about his earlier work with Marc Raichle on anticorrelated networks in the brain, his work on TMS network mapping, lesion network mapping and DBS network mapping. Our conversation was enriched by guest questions of many friends and members of the center, Shan Siddiqi, Aaron Boes, Michael Ferguson, Fred Schaper and Dan Corp. We cover how lesion network mapping originated, why effective invasive and noninvasive neuromodulation targets must be linked by brain networks and ways Mike has taken to uncover those relationships. We talk about what makes causal sources of inference – brain lesions and neuromodulation targets – so unique to study the brain, treatment concepts that can be traced back to basic science work in animals vs. serendipitous findings in humans and discuss why and how brain lesions are set for a comeback – both for treatment and investigation.

It was my great pleasure to talk with Marie Krüger, who is currently leading the stereotactic surgery unit in St. Gallen but is on her move to join the team at UCL / Queensquare London. Marie trained in Freiburg, Germany, with Volker Coenen and Peter Reinacher, where she ran multiple studies about segmented electrodes and how to localize their directionality. After that, she carried out a fellowship with Chris Honey in Vancouver, where she developed a protocol of DBS for dental pain and was involved in studies about DBS for spasmodic dysphonia. Her concept of treating dental pain was creative: Since it was not exactly known, which nucleus would result in the best benefit, she implanted segmented leads into the triangle border between three adjacent thalamic nuclei. That way, she could probe exactly which one would deliver best therapeutic benefit. In London, she will work on establishing the new MRgFUS device to treat patients without the need for incisions or anaesthesia.

One of five adults in the United States suffers from a diagnosable mental illness at any one point in time. The burden of psychiatric diseases is massive on both personal and economic levels. It was a great honor to talk to Dr. Joshua Gordon, director of the National Institute of Mental Health. We covered finding a balance between i) running this entity with a budget of 1.6 billion USD and 3000 grants at any one time and ii) pursuing his own research using optogenetic methods to dynamically modulate circuits in the brain. We talked about key strategies of the NIMH, such as the Research Domain Criteria Framework (RDoC) and it's evolution over the last decade up to the present day, the importance to balance between predictive and normativ/generative models, the importance of studying dynamics and to map symptoms to circuits in the brain. There are few if not any critically useful biomarkers we have in the field of psychiatry – we discussed why that is the case. Also, we dived into basic science vs. serendipitous discoveries and the power of either one (or the combination of the two) to move our field forward. Covering Dr. Gordon's own scientific agenda, we discussed the work of his lab on the dynamics between the prefrontal cortex and hippocampus, as well as the significance of this work for models of anxiety and schizophrenia.

It was my great pleasure to talk with Nolan Williams, who is the mind behind the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol for treatment of depression. In this drastically intensified protocol, Fifty sessions of 1,800 pulses are delivered as 10 daily sessions over just 5 days – condensing what usually takes months to a single week. After making hands-on experience with deep brain stimulation, Nolan wanted to first work with this invasive technique in depression. His mentors told him that it wasn't a good time for DBS in depression, given two randomized trials had just failed, so he turned to noninvasive stim and realized, that – in comparison to DBS – we were heavily understimulating the brain, i.e., by far not delivering as many pulses in a given time interval. He also realized that the optimal targeting could not be determined by electrophysiology, but gladly Mike Fox had worked out a good method using resting-state fMRI. This way, the SAINT protocol was born, leapfrog-jumping the way we apply TMS to treat depression. After undergoing SAINT, 19 of 21 patients (90.5%) met remission criteria after a single week of TMS.

The tenth DBS Think Tank is about to happen in Gainesville, Florida next month – so it's timely to talk with the masterminds behind it: Michael Okun and Kelly Foote need no introduction in the field & represent a role-model power-couple of how neurosurgery and neurology can join forces to build something unique. In Gainesville, they built one of the most important DBS programs in the world, essentially from scratch, after setting their minds to this goal during residency. We talk the concepts behind the Think Tank, their work on the DBS Tourette's Disease registry, the importance of collaborations in the field and future / (present?) concepts such as adaptive DBS, their «tick detector» (about which we could already hear in episode #21 between Aysegul Gunduz and Julian Neumann) and the general future of the field.

Following a fascinating talk Aryn gave at OptoDBS 2022, we talk about her work on optogenetically inspired deep brain stimulation for Parkinson's Disease. In a first paper (2017 Nature Neuroscience), Aryn's lab could establish that a specific lineage of cells in the external pallidum needed to be stimulated (or a second one suppressed) to achieve symptom relief in the 6-OHDA mouse model of Parkinson's Disease. Crucially, these effects outlasted the stimulation, sometimes by up to eight hours. In a second paper (2021 Science), her team was able to mimick the exact same effect using a very creative form of deep brain stimulation to the entopeduncular nucleus. I am convinced that these results could transform the way we apply DBS in humans and they form a template of successful translation from optogenetics to electical stimulation. In a way, Aryn's story of discovery very much resemble the ones by Anne Young (previous episode), both were puzzled that differentially modulating specific – not all – cells (for Anne D1 vs. D2 cells in the striatum & Aryn Pv+ vs. Lhx6+ cells in the pallidum) would have an effect on Parkinsonism. I hope you will be as fascinated by the conversation I had with Aryn, as I was!

In this episode, I had the tremendous honor of speaking with Anne Young about the many highlights of her career, including key evidence that established Glutamate as a neurotransmitter, as well as her work on Huntington's Disease. Directly building upon the preceding episode with Mahlon DeLong, we now hear about the Ann Arbor Side of the so-called “Albin-Delong” model, which was equally informed by the team of Anne Young & her late husband John Penney alongside Roger Albin. In 1991, Dr. Young was appointed chief of neurology at Massachusetts General Hospital and with that the first female service chief in the hospital's 180-year history and the first female chief of neurology at a teaching hospital in the United States. During her career, she was president of both the American Neurological Association and the Society for Neuroscience – which so far nobody else has achieved. We take these unique achievements as examples to talk about success, leadership and career advice, while also covering a bit of the struggles and challenges associated with a clinician-scientist career.

In this episode, I had the great pleasure of speaking with Mahlon DeLong about the past and future of our field, the most influential model of the basal ganglia circuitry, microexciteable zones in the striatum, the role of the nucleus basalis in Alzheimer's Disease and many other topics. We also touch upon the role of the basal ganglia model for psychiatry, more recent topics such as psychedelics or how instrumental the MPTP model for Parkinson's Disease in nonhuman primates was. Mahlon needs no introduction and can certainly be seen as one of the key founding fathers of modern basal ganglia research and together with Hagai Bergman and Thomas Wichmann directly paved the way to establish deep brain stimulation to the subthalamic nucleus. The episode is enriched by guest questions from Marwan Hariz and Hagai Bergman, as well as planning input from Helen Mayberg. I hope you enjoy the episode with Mahlon as much as I did and thank you for tuning in!

In this episode, Aysegul Gunduz & Julian Neumann speak about Ayse's exciting work on closed-loop DBS in tremor, their tic-detector, and thriving as an engineer in a medical field such as DBS. They also touch upon minority groups in the field. The main focus of their 2020 Science Translational Medicine study, in which Ayse's team developed and studied a chronically embedded cortico-thalamic closed-loop deep brain stimulation system for treatment of essential tremor – clearly a landmark study in the field that brought together advances in engineering and medical research. Ayse also speaks about industry collaborations and the value of novel devices that enable scientific studies that had not been possible, in the past. I hope you enjoy the conversation between Ayse and Julian as much as I did and thank you for tuning in!