#79 Karl Friston: The Origins of SPM and the Making of Modern Human Brain Mapping

Karl Friston is one of the most influential neuroscientists of our time and a central figure in the history of human brain mapping. Many listeners will know him for the free energy principle, active inference, dynamic causal modeling, voxel-based morphometry, and many other theoretical contributions.In this episode, we take a different route and go back to the early history of Statistical Parametric Mapping, or SPM: the software and statistical framework that helped turn functional neuroimaging from a local craft into a shared scientific language.We discuss how Karl moved from psychiatry into brain imaging, what the first PET activation experiments felt like, how SPM emerged at the MRC Cyclotron Unit and later the Functional Imaging Laboratory, how the software spread through the neuroimaging community, and how key collaborators helped shape modern PET, fMRI, VBM, DCM, EEG, and MEG analysis.We also talk about mentorship, the culture of the FIL, open software, MNI space, spatial normalization, and what it means for a scientific tool to become infrastructure for an entire field.

In this episode of Stimulating Brains, I speak with Keith R. Mullett, who can uniquely tell a part of the DBS history that is often skipped.We often begin the story of modern DBS in Grenoble around 1987, when Alim-Louis Benabid and colleagues showed that high-frequency VIM stimulation could suppress tremor. Keith reminds us that Medtronic's first DBS system had already been implanted in 1969, not for tremor or Parkinson's disease, but for severe chronic pain. Keith joined Medtronic in May 1972 and spent 37 years there, first in Minneapolis and later at the Bakken Research Center in Maastricht, where he arrived shortly after Frans Gielen.The conversation goes back before the Benabid era, into the period when Medtronic and its physician collaborators built the devices, surgical know-how, clinical relationships, and regulatory experience that later made DBS for movement disorders possible. We discuss Yoshio Hosobuchi and the first pain implants, RF systems with belt-worn transmitters, the transition from cardiac pacing to neurostimulation, the FDA call for data, ITREL, the Bakken Research Center, and the 1992 tremor study: the moment Keith describes as "the rest is history."This episode also connects to our recent conversations with Todd Langevin (episode 46) and Frans Gielen (episode 75). Todd described the internal venturing and business side of DBS after Benabid, while Frans described the engineering, clinical studies, training, imaging, and new indications that followed. Keith, who was Frans' boss, helps us ask what had to exist inside Medtronic before those later teams could build the modern field.

In this episode of Stimulating Brains, I’m honored to speak with Mary Elizabeth Sutherland, a Deputy Editor at Nature whose areas of responsibility include cognitive neuroscience and a broad range of the behavioural and social sciences. If you work with clinical or human neuroscientific data in the field of brain stimulation and choose to submit to Nature, chances are high that Mary Elizabeth will handle your work.Before moving into scientific publishing, she studied at Cornell, completed her PhD at McGill, and did postdoctoral work in Santiago, Chile. Her own research background includes auditory cognitive neuroscience and music cognition. I’m especially looking forward to talking with her about what the job of a Nature editor actually looks like, how editorial decisions are made in a journal with limited space and broad ambition, how human studies are evaluated in that setting, and where scientific publishing may be heading next.The conversation moves through career paths into editorial work, the day-to-day work of a Nature editor, how scientists become professional editors, and the bar for publishing in Nature, with an emphasis on the choices, constraints, and judgments that shape Mary Elizabeth Sutherland's work.

In this episode of Stimulating Brains, we are honored to sit down with György Buzsáki, Professor of Neuroscience at New York University and one of the most influential thinkers in modern neuroscience.Dr. Buzsaki trained as a physician in Hungary, completed his PhD in neuroscience at the Hungarian Academy of Sciences, and went on to postdoctoral training in North America before building a decades-long academic career spanning UC San Diego, Rutgers University, and now NYU.In this conversation, we explore the ideas behind his work on hippocampal oscillations, sharp-wave ripples, and the organization of neural activity across states such as sleep and wakefulness. Dr. Buzsáki reflects on how his early life experiences, technological innovation, and persistent questioning of dominant frameworks shaped a scientific philosophy centered on internal dynamics rather than task-based explanations.Tune in for a rare opportunity to hear one of neuroscience’s most original voices reflect on the past, present, and future of understanding the brain.

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.