Stimulating Brains

In this episode, Julian Neumann and I talk about his research toward adaptive deep brain stimulation. Julian has recorded local field potentials from DBS electrodes implanted in patients with Parkinson's Disease, dystonia, essential tremor, obsessive compulsive disorder and depression and is a true expert on the mechanism of action of DBS. With his laboratory for interventional & cognitive neuromodulation, he has recently ventured into machine-learning based applications to decode brain states from local field potential and electrocorticography recordings in the human brain. We talk about a multitude of conventional and novel physiomarkers that are envisioned for use to guide adaptive (or closed-loop) DBS applications in a tour-de-force across DBS targets, indications and concepts.

In this episode, Peter Snyder and I talk about Jose Delgado, one of the inventors of deep brain stimulation. Peter's father, Dr. Daniel R. Snyder, served as Delgado’s last American-trained post-doctoral fellow at Yale in the early 1970s – and took over the laboratory at Yale when Delgado moved back to Madrid. We get a good feeling about Delgado as a scientist, his many inventions, his relationship with the media and his grand-plan toward a 'psychocivilized society' that would control behavior by means of neuromodulation. Together with others, Peter wrote a book called 'Science in the Media', in which he uncovers a quite spectacular deceit in the way Delgado communicated to journalists and the media about his famous 'brave bull' demonstration at a bull ranch in Cordoba, Spain. The bull demonstration – in which Delgado remote controlled a 'brave, angry, and dangerous beast' into a docile animal by the push of a button – is certainly a famous cornerstone in the history of neuromodulation. In this episode, we can learn from Peter that, in a way, it was a certain scam – or at least has been overinterpreted by the media and even most researchers in our field.

You have met Ben Stecher in episode #12 already – today we follow up on his very own account of deep brain stimulation after Ben has now lived with DBS to his subthalamic nucleus for 3 month. Ben is joined by Alberto Espay, who is a world-renowned expert on Parkinson's Disease from UC health in Cincinnati, Ohio. Together, Alberto and Ben wrote “Brain Fables”, a book with the aim to debunk some of the common (mis)conceptions in the field of neurodegenerative diseases. The book recently won the prose award by the Association of American Publishers in the category Neuroscience and is truly unique in its way to combine both the views of patient and health professional on the matter. We also touch upon a recent debate at the 2021 International Movement Disorders Congress (MDS) between Alberto Espay and Patrick Brundin, about the question whether clearing α-synuclein enough to treat Parkinson’s disease. Alberto and Ben take us on a fascinating journey to think outside of the box, to question and challenge currently accepted views about the etiology of Parkinson's Disease and about their vision of how to conquer neurodegenerative diseases.

It was a tremendous privilege to pick Mark Humphrey's brain who has insight about broad domains of the brain like few others. His new book The Spike: An Epic Journey Through the Brain in 2.1 Seconds takes us on a journey through the brain starting at the retina and ending in the spinal cord. As we follow spikes along, we learn how information is processed in the brain, but also how it's simply lost and forgotten. Mark has done his PhD with Kevin Gurney, who together with Tony Prescott and Peter Redgrave has published an influential computational model of the basal ganglia in 2001. We disentangle how it differs from the Albin-DeLong model, talk about implications for whole-brain computational models and the mechanism of action of DBS. Based on a twitter thread that Mark once published about the Wishaw decorticate rat experiments, I ask him: Does the brain even need the cortex? Finally, we touch about compression of data and his recent paper about a weak and strong principle of dimensionality reduction of the brain.

Benjamin Stecher is doing impressive work in is role a scientific writer and patient advocate. He co-authored the book “Brain Fables” together with Alberto Espay, which recently won the prose award by the Association of American Publishers in the category Neuroscience. The book is truly unique in its way to combine both the views of patient and health professional on the history and misconceptions of Parkinson's Disease and what should change in our field to make progress. Benjamin was diagnosed with Parkinson's disease at 29. Since then, he left a successful managing partner position in Shanghai to study the disease full time. He has been traveling the world to witness the latest and greatest progress being made in over 100 research laboratories around the globe. He has interviewed over 80 international experts and shares his insights on the website tmrwedition.com. On June 2nd, Benjamin underwent deep brain stimulation surgery to the subthalamic nucleus. We are incredibly grateful that a mere nine days after that, he shares this experience lived from the most direct and intimate, the most important perspective: the one of the patient.

Katrin Amunts is the Scientific Research Director of the Human Brain Project and leads two centers at Forschungszentrum Jülich and the University Hospital Düsseldorf. With her internationally recognized work that includes the BigBrain and JuBrain projects and use of novel methodology such as polarized light imaging, she follows the footsteps of famous anatomists of the past, such as Cecile and Oskar Vogt, name givers of her institute. We talk about the relevance of anatomical models and ultra-high-definition atlases for successful deep brain stimulation procedures, the impact of open data sharing and upcoming advances in the field of whole brain anatomy.

Cameron McIntyre and I talk about biophysically plausible deep brain stimulation models that his laboratory has established and continues to refine since about 20 years. Cameron shares insights from a time where DBS modeling was not a thing – how his career choice to step into the realms of medical hospitals as a biomedical engineer had been risky or at least unusual at the time. We learn why the VTA model was originally a step backwards and why there is a large difference between inventions & prototypes vs. commercially useable products with direct clinical impact. Cameron shares his insight on why DBS modeling for movement disorders and for neuropsychiatric diseases are currently asking very different levels of questions. We touch upon amazing recent inventions by the McIntyre lab – such as the holographic basal ganglia pathway atlas and the HoloDBS system to plan surgeries – collaboratively and remotely from different living rooms throughout the United States.

Mac Shine and I talk about Mac's recent intriguing opinion paper that may have radical implications for systems and clinical neuroscience. In it, the thalamus mediates between feed-forward type input from cerebellum, sensori nuclei and cortex one one hand and input from the basal ganglia that introduces an element of randomness. By projecting to the cortex in a specific manner, the thalamus can recruit these inputs to shape the attractor landscape of cortical activations. Mac develops this a theory from the cell- to the systems neuroscience level and hints at how Kahneman's system I and II levels of thinking fast and slow could be implemented in the brain. The theory radically extends and partly opposes existing concepts such as the thalamus as a mere relay station and the model of the basal ganglia for action selection proposed by Alexander, DeLong and Strick in 1989 – so there is vast potential of this becoming transformative for deep brain stimulation, as well.

In this guest episode, Luka Milosevic talks with Mojgan Hodaie about the neuromodulation for neuropathic pain, how serendipity may lead to a whole novel research field, how our teachers shape the way we think about the brain and how we may learn from each single patient we get in contact with. Prof. Hodaie is a world-wide expert in stereotactic surgery with a special focus on (imaging guided targeting of) neuropathic pain. The Hodaie lab published the seminal article demonstrating the feasibility of detailed imaging of the course of the cranial nerves in the posterior fossa and a method in which these relate to tumours that arise there, particularly acoustic neuromas. Prof. Hodaie is a member of the executive board of the Foundation for International Education in Neurological Surgery (FIENS) and the founder of the NEURON project (www.neuronproject.org).

In this episode, we talk with Patricia Limousin about the early days of DBS in the modern era to the current day and about what the future may hold. Building up on episode #4 with Pierre Pollak, we find out how Patricia experienced programming the first bilateral STN-DBS patient, and what has changed over the last 30 years. Professor Limousin has worked at the UCL Institute of Neurology and the National Hospital for Neurology & Neurosurgery since 1997, where she is currently a Professor of Clinical Neurology and Consultant Neurologist. We follow her journey from a PhD with the topic of subthalamic nucleus DBS in Grenoble/Lyon to her move to London, where she helped build one of the leading DBS centers, worldwide.