Stimulating BrainsSep 22, 2023
#40: Casey Halpern – Novel indications and approaches to invasive neuromodulation and neuroscience
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!
#39: Nico Dosenbach – A BOLD Challenge to Penfield’s Homunculus based on resting-state fMRI
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.
#38: Espen Dietrichs – about Carl Sem-Jacobsen, the true inventor of subthalamic DBS in Norway
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.
#37: Jon Nelson – DBS for Depression saved my life: Defying Stigma in Mental Health
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.
#36: Béchir Jarraya & Jordy Tasserie – Unlocking Consciousness: Neuromodulation, Neurofeedback, and the Future of Brain Science
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.
#35: Mark Richardson – Surfing the Frontiers of Functional Neurosurgery: From Brain Modulation to Patient Engagement
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.
#34: Charles Jennings – From Graduate School to Founding Editor of Nature Neuroscience and Beyond
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.
#33: Joachim Krauss, Marwan Hariz, & Christian Moll – The History of Stereotactic and Functional Neurosurgery and Serendipity
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.
#32: Philip Mosley – Neuropsychiatric network effects of DBS in Parkinson's and OCD
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!
#31: Veerle Visser-Vandewalle – Operating on the first neuropsychiatric DBS case in the modern era
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!)
#30: Suzanne Haber – Anatomists, an endangered species & their importance for DBS
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.
#29: Mike Fox – Finding Therapeutic Treatment Targets using Causal Brain Connectomics
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.
#28: Marie Krüger – Segmented Contacts & DBS for Dental Pain
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.
#27: Joshua Gordon – Neuromodulation from genes to cells to circuits to behavior
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.
#26: Nolan Williams – A Noninvasive Neuromodulation Revolution?
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.
#25: Michael Okun & Kelly Foote – DBS Think Tank, Connectedness, Closed-Loop & Tic-Detectors
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.
#24: Aryn Gittis – Optogenetically inspired DBS for Parkinson's Disease
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!
#23: Anne Young – Basal Ganglia Circuitry, Glutamate & Leadership
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.
#22: Mahlon DeLong – The Basal Ganglia in Health & Disease
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!
#21: Aysegul Gunduz – Engineering in DBS, closed loop & brain sensing
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!
#20: Christian Lüscher – OptoDBS and how we bring back the neuron into neurology
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.
I hope you enjoy the conversation with Christian as much as I did and we both hope to see you this June in Geneva for OptoDBS 2022!
#19: Sameer Sheth – Neuromodulation for Psychiatry – the last frontier?
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.
#18: Jeffrey Hausdorff – The Present and Future of Non-Invasive Brain Stimulation in Aging and Parkinson’s disease Research
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.
#17: Hagai Bergman – The Hidden Life of the Basal Ganglia: At the Base of the Brain and Mind
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.
#16: Julian Neumann – Machine-Learning for adaptive Deep Brain Stimulation
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.
#15: Peter Snyder about Jose Delgado: Remote-controlling the brain
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.
#14: Benjamin Stecher & Alberto Espay – Challenging "brain fables" about neurodegenerative diseases
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.
#13: Mark Humphries – Basal Ganglia Models, Highs and Lows in the Brain and… how does DBS work?
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.
#12: Benjamin Stecher – A personal account of Parkinson's and Deep Brain Stimulation
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.
#11: Katrin Amunts – A modern take on human brain anatomy and its relevance to DBS
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.
#10: Cameron McIntyre – Pushing the frontier of biophysically plausible DBS models
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.
#9: Mac Shine – A thalamus-centric view of basal ganglia, cerebellar and cortical interactions
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.
#8: Mojgan Hodaie – Connectivity aided targeting in neuromodulation for neuropathic pain
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).
#7: Patricia Limousin – Subthalamic Nucleus Stimulation: From Parkinson's Disease to Obsessive Compulsive Disorder
#6: Lone Frank – Robert Heath, the forgotten inventor of Deep Brain Stimulation
In this episode, Lone Frank shares insight about her book “The Pleasure Shock: The Rise of Deep Brain Stimulation and Its Forgotten Inventor” in which she delved into the academic life of a true pioneer of our field. Robert Heath invented deep brain stimulation in the 1950ies and was a remarkable pioneer of our field. Lone's book takes us on a trip delving deep into the discoveries – but also controversies around Heath and his contemporaries, such as José Delgado and Frank Ervin.
#5: Günther Deuschl – On the importance of transforming Deep Brain Stimulation to evidence based medicine
In this episode, Günther Deuschl shares insight about his life in neurology and the endeavors to transform deep brain stimulation for movement disorders as established treatment options supported by class one evidence. He has been instrumental in multiple major clinical trials, such as the randomized double-blind clinical trial for DBS to the subthalamic nucleus in Parkinson's Disease (Deuschl et al. 2006), a similar study for modulation of the internal pallidum in dystonia (Kupsch et al. 2006) and later the Earlystim trial (Schuepbach et al. 2013) – all published in the New England Journal of Medicine. He was president of the International Movement Disorders Society (MDS) from 2011-2013, Editor in Chief of the journal Movement Disorders and has been awarded numerous high-class awards in our field. He is an international capacity in the field of tremor and leads the study group for tremor in the MDS.
Günther Deuschl takes us on a fascinating journey into the past – where DBS was not as established as it is today – the present and the future – with emerging technologies such as MR-guided focused ultrasound and neuromodulation for psychiatric diseases.
#4 Pierre Pollak – How modern-day Deep Brain Stimulation for movement disorders was introduced in Grenoble
In this episode, Pierre Pollak shares insight about his life in neurology, music and sports and how he introduced modern-day deep brain stimulation for movement disorders together with Alim Louis Benabid and the team in Grenoble in 1987. After his retirement from academia and neurology, Pierre took up playing piano and spending time with physical activity (cycling, winter sports, etc) – and he mentioned that our conversation was the first about deep brain stimulation he had in over five years.
He talks about the first patients that received deep brain stimulation for tremor – the first one using an externalized stimulator approved for animal use only over the course of three weeks. We then advance to the incredible anecdote of how Patricia Limousin switched on the first bilateral STN stimulation to treat a patient suffering from severe akinetic Parkinson’s Disease. For both, it was incredible how the patient could walk – without any help from pharmacological drugs.
#3: Marwan Hariz – a strong role for imaging and being critical in the field of DBS
In this episode, Marwan Hariz shares insight about why imaging is both the past and the future for deep brain stimulation, how its role of being the “court jester” or “stereotaxy police” emerged and why critical discussions are important for our field.