Stimulating Brains

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.

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.

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.

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.

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!

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!)

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.

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.

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.

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.