Stimulating Brains

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.

In this episode I had the honor to speak with Christian Lüscher about his exciting work on neuromodulation in addiction as well as the upcoming OptoDBS conference which he has been organizing since 2015 in Geneva. We cover Christian's milestone works in creating and refining a model of addiction in the brain, ways to counteract addiction using both optogenetics and DBS and why only about twenty percent of mice with unlimited access to drugs will become addicted. We discuss examples of optogenetically informed DBS by the Lüscher lab and recent milestone work by Aryn Gittis. OptoDBS has unique setup of joint sessions with similar topics by speakers from the optogenetics & DBS fields, respectively. The aim is to derive at optogenetically informed concepts for DBS – which could be implemented to change clinical practice. I have the great honor to co-host this years' conference and we discuss the anticipated highlights of OptoDBS and what we are most excited about.

In this episode I had the honor to speak with Sameer Sheth about recent advances in deep brain stimulation for psychiatric indications. We focus on two recent publications, a paper published in Biological Psychiatry that introduced a revolutionary novel concept of treating depression by inserting stereo-EEG electrodes to determine the individual circuitry involved in each patient's disease. The second was published in Nature Medicine and involved long-term local field potential recordings carried out during daily live in patients with obsessive compulsive disorder.

It was a very unique opportunity to learn more about the background on how these studies originated, how they were carried out, and what the future may bring for this exciting field & I hope you enjoy the conversation I had with Sameer as much as I did.

In this guest episode, Jeffrey Hausdorff and Nathan Morelli speak about transcranial direct current stimulation (tDCS), its mechanisms of action, current application in research, and where the field is going in the future. In this discussion, we cover many topics which will give you insight into this area of brain stimulation. We begin with the basics of tDCS from its historic origins and therapy fundamentals. Our discussion then progresses to a deep-dive inside some of Prof. Hausdorff's most recent works in collaboration with many world renowned researchers in neurodegenerative disease – notably including recent findings in using tDCS to mitigate freezing of gait in patients with Parkinson’s disease. We close with a look into the future of tDCS in research and clinical practice. Given Prof. Hausdorff’s expertise there are few people in the world more qualified to speak on Parkinson’s disease and non-invasive brain stimulation. As such, it is our immense privilege to present this interview to you.

In this episode, Hagai Bergman and I talk about his new book, The Hidden Life of the Basal Ganglia: At the Base of Brain and Mind. We cover some of the many highlights of his life in basal ganglia and deep brain stimulation research. This includes his crucial discovery that paved the way to subthalamic deep brain stimulation during his work at John Hopkins together with Mahlon DeLong and Thomas Wichmann. We talk about his three-layer model of the basal ganglia, one of the first proof-of-principle demonstrations of closed-loop DBS, his work on the basal ganglia as a dimensionality reduction system and his newer interest in asleep DBS (and basal ganglia electrophysiology during sleep). We also talk about collaborations and friendships between academia and industry, as his research has found commercial applications such as in the HaGuide algorithm in the NeuroOmega system by AlphaOmega. Together with the surgeon of his center, Zvi Israel, Hagai has carried out over seven hundred DBS surgeries as a pair of two – and he has further studied DBS electrophysiology in numerous experiments in the macaque model. Likely, there are few if no people around that know the basal ganglia as well as Prof. Bergman. Hence, it was a true privilege to carry out this in-depth conversation about the key concepts of his research with him.

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.