#75: Frans Gielen – From Idea to Evidence: The Making of Modern DBS

In today’s episode of Stimulating Brains, we have the pleasure of speaking with Frans Gielen — a physicist and biomedical engineer who played a foundational role in shaping modern deep brain stimulation. Over more than three decades at Medtronic, Frans worked at the intersection of engineering, neurology, and surgery during the formative years of DBS, when stereotactic imaging protocols, targeting strategies, and surgical workflows were still being defined in real time.He supported and trained teams in more than 2,000 DBS implantations worldwide, helping refine operative techniques and imaging standards long before they became routine. Beyond the operating room, Frans designed and managed several of the pivotal clinical trials that ultimately led to CE marks in Europe and FDA approvals in the United States — including landmark studies in VIM DBS for tremor, STN and GPi DBS for Parkinson’s disease, the first controlled trial of DBS for obsessive–compulsive disorder, and later the MORE trial in epilepsy.In this conversation, we explore the practical, technical, and regulatory work required to transform DBS from a promising idea into a reliable, evidence-based therapy — and reflect on what it took to build the foundations that the field stands on today.

In this episode of Stimulating Brains, we sit down with Dr. Ludwig Zrinzo, Professor of Functional Neurosurgery at University College London and Head of the Functional Neurosurgery Unit at Queen Square.Drawing on decades of experience at the forefront of deep brain stimulation, Dr. Zrinzo reflects on the evolution of DBS from awake procedures to image-guided surgery under general anesthesia, emphasizing why precision, verification, and closing the loop are essential for improving patient outcomes.We discuss how his experience shaped a rigorous, data-driven approach to targeting, why imaging quality remains a very critical factor in DBS accuracy, and how systematic post-operative verification transformed clinical practice. Beyond technique, Dr. Zrinzo shares deeply insightful perspectives on patient selection, mentorship, leadership, and the responsibility of building sustainable teams in academic neurosurgery.The conversation also ventures into neuropsychiatric DBS, including OCD, where we examine how stimulation in different targets may have differential effects on behavior, illuminating the brain’s underlying circuitry. Finally, we look into the future of adaptive and closed-loop stimulation, emerging electrode technologies, and the future balance between innovation, scalability, and patient-centered care.Tune in for a thoughtful and wide-ranging conversation on precision, evidence, and humanity in brain stimulation — and on how functional neurosurgery continues to teach us how the brain truly works.

In this episode of Stimulating Brains, we sit down with Dr. Eyal Zadicario, Chief Operating Officer at Insightec, to explore the remarkable evolution of focused ultrasound – from its experimental origins to its transformative role in functional neurosurgery today.Dr. Zadicario shares insights from over two decades at the forefront of innovation, reflecting on the challenges of translating breakthroughs from academia to industry, designing clinician-friendly systems that prioritize the patient experience, and overcoming skepticism toward disruptive technologies.Together, we revisit key milestones – from the first MRgFUS based thalamotomy in 2008 and early applications in breast cancer, to the expanding frontiers of neuromodulation. Looking ahead, we discuss the exciting possibilities of blood brain barrier opening, the acoustic neurosurgical suite, and even brain mapping through focused sound.Tune in for a fascinating conversation on how precision acoustics are reshaping the landscape of brain therapy and beyond.

Today, we had the privilege of speaking with Dr. John Rolston, a leading voice at the intersection of neurosurgery, epilepsy, and brain stimulation.Dr. Rolston is an Associate Professor of Neurosurgery at Harvard Medical School and the Director of Epilepsy Surgery at Brigham and Women’s Hospital. His pioneering work bridges clinical neurosurgery and computational neuroscience, focusing on how electrical stimulation can modulate dysfunctional brain networks to treat epilepsy, movement disorders, and disorders of consciousness.In this episode, we explored the complexities of neuromodulation—what makes stimulation effective, why patient-specific targeting matters, and how brain states influence therapeutic outcomes. Dr. Rolston also shared his lab’s work on traveling waves in the brain and how these insights are transforming seizure localization and surgical decision-making. From closed-loop stimulation to stem cell therapy for Parkinson’s disease, Dr. Rolston walks us through the evolving landscape of functional neurosurgery and its future.

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.