#61: Shan Siddiqi – Bringing Human Brain Connectomics to Clinical Practice in Psychiatry

In this episode of Stimulating Brains, we're thrilled to have Jim McNasby join us. Jim is a deep brain stimulation (DBS) patient and the Chief Counsel at the Michael J. Fox Foundation. Jim has an inspiring story, not just as a DBS patient but also as a legal professional working at the forefront of Parkinson’s research advocacy. We’ll dive into his personal experience with DBS—how it has shaped his life since his diagnosis in 2000 and his surgery in 2019—and explore his crucial role at the Michael J. Fox Foundation, where he helps drive forward their mission to find a cure for Parkinson’s disease. I had the pleasure of hearing Jim speak at the Neuromodec Conference, where he shared a powerful story of how DBS transformed his life, even showing a video that vividly captured its positive effects. We’ll talk about that, his DBS wishlist, and the work he’s doing to advocate for patients and drive research. In this episode, we explore his personal experiences, the impact of DBS, and his role in advancing Parkinson's research and advocacy at the foundation. Jim also reflects on the transformative moment when his DBS was first activated and discusses his vision for the future of patient care and innovation in the field.

Today, we have the pleasure of speaking with Dr. Bálint Várkuti, a distinguished expert in the field of neuromodulation. Dr. Várkuti is the founder and CEO of CereGate, a pioneering company developing brain-computer interface technologies—referred to as computer-brain interface technologies—that aim to enhance neuromodulation therapies. Before founding CereGate, Dr. Várkuti made significant contributions to image-guided DBS programming solutions at Brainlab. With over a decade of experience in neurotechnology and the medical device industry, his work focuses on designing innovative interfaces between technology and the human brain to improve patient outcomes. For those familiar with DBS, you’ll understand the nuances here: when stimulation of the super-dynamic nucleus in DBS is set too high, patients often experience a tingling or irritating sensation due to overstimulation of sensory fibers. Typically, this side effect is avoided. However, Dr. Várkuti had a groundbreaking insight: This sensation represented a channel of information with the brain – and one could make use of it! In a nutshell, CereGate leverages these overlooked pathways, using them in a patterned and complex way to transmit information that the brain can decode. This approach opens up new possibilities for interfacing with the brain, which we find truly fascinating: This concept that CereGate is exploring might just be the start of a much larger field of innovation.

In this episode, we have the pleasure of hosting Mark McAuley, a deep brain stimulation (DBS) patient and the CEO of Astronomy Australia Limited, and Dr. Susan Boehnke, an Associate Professor at Queen’s University in Canada and director of the Neurotech Microcredential Program and the Neurotech Discovery Lab. Together, they've been part of remarkable efforts that not only focus on the practical and ethical aspects of neurotechnology but also engage students in real-time research. Mark brings over thirty years of experience in research and development, with a remarkable track record of securing $300 million in Australian Government grants for major research infrastructure projects. Holding degrees in astrophysics, ancient history, and an MBA—where he was awarded the Vice-Chancellor’s medal as the university's highest-achieving postgraduate student—Mark was diagnosed with Parkinson’s disease in 2010 and received a DBS implant in 2020. Post-surgery, he's been a passionate advocate for better patient care and improved DBS programming to enhance clinical outcomes. Dr. Susan Boehnke completed her PhD in Neuroscience at Dalhousie University and has an extensive background in auditory neuroscience and primate neurophysiology. She led the creation of one of the first non-human primate models of Alzheimer’s disease and established Canada's first non-human primate biobank. In response to the explosion of interest in neurotechnology, she's now pioneering a micro-credential program in neurotech and exploring the ethical issues surrounding it. She's also leading the Training Committee for Connected Minds, a significant research initiative between York and Queen’s Universities. At the recent Neuromodec conference in New York, Mark and Susan presented their work, which emphasizes patient inclusion in research—a theme Dr. Boehnke passionately advocates for—and provides transformative learning experiences for students. Today, we'll dive into their journeys, the science behind their projects, and explore potential insights into the future of patient-led research and education in neurotechnology.

In today’s episode, we dive deep into two groundbreaking studies led by Daniela and Clément. We explore their 2022 Nature Communications paper on using cerebellar stimulation to alleviate levodopa-induced dyskinesias in Parkinson’s disease and discuss their 2023 paper uncovering the cerebellum’s role in regulating fear extinction through its connections with the thalamo-prefrontal cortex pathway. Along the way, we discuss how these discoveries may open up exciting new possibilities for treating both motor and emotional disorders. Tune in for an insightful conversation packed with cutting-edge science and exciting future perspectives!

In this episode, I was able to talk to Dr. Shan Siddiqi, who is an Assistant Professor of Psychiatry at Harvard Medical School and a researcher at the Center for Brain Circuit Therapeutics at Brigham and Women’s Hospital, where he and his lab focuses on brain circuit therapeutics. Shan’s work bridges the gap between neuroimaging and causality, exploring the mechanisms of brain stimulation and lesions in neuropsychiatric disorders such as depression and post-traumatic stress disorder (PTSD). He’s made remarkable strides in understanding the brain circuits involved in these conditions and how we can leverage this knowledge for neuromodulation therapies. Shan has worked on numerous topics that focus at improving transcranial magnetic stimulation (TMS) for psychiatric indications by using brain connectomics. Using various causal sources of information, he was able to show that the same network is associated with changes of depressive symptoms in patients with brain lesions, major depression, epilepsy or Parkinson's disease – and this network could be identified using various types of brain lesions, transcranial magnetic or deep brain stimulation sites. More recently, Shan has worked on identifying a novel TMS target for PTSD based on data from penetrating head trauma lesions and TMS sites. He has worked on conceptual papers that revolve around closing the causality gap in neuroimaging, as well as on how to bring connectomics into clinical practice in psychiatry. His recently launched prospective R01 funded trial will aim at prospectively mapping random cortical stimulation sites to various behavioral and clinical outcomes.

In this episode, we’re joined by Dr. Suthana, a leading neuroscientist from UCLA's David Geffen School of Medicine and the Jane & Terry Semel Institute for Neuroscience & Human Behavior. Dr. Suthana’s career sits at the intersection of neuroscience, neural technology, and engineering, focusing on memory disorders and innovative brain technologies. We explore her groundbreaking research on memory enhancement through deep brain stimulation (DBS), focusing on a study where stimulation of the entorhinal cortex enhanced memory retention during learning. She also delves into the challenges of translating laboratory findings into real-world clinical improvements. In a truly unique part of her work, Dr. Suthana uses virtual reality (VR) and mobile tech to study memory in naturalistic settings. Her lab even developed a custom backpack system, allowing participants to move freely while recording real-time brain activity to better understand memory and spatial navigation. We also discuss her recent work on PTSD, where she uses responsive stimulation in the amygdala to help reduce trauma-triggered responses. Dr. Suthana expresses her excitement about the future of wearable tech and how it might revolutionize the field by combining real-time data collection with neurostimulation. Tune in for an inspiring look at the future of neuromodulation and memory enhancement as Dr. Suthana shares her vision and insights into this cutting-edge field.

As a fourth installment of this podcast into key industry leaders in neuromodulation, this is our conversation with Milad Girgis, who is the VP and General Manager of the Brain franchise at Boston Scientific. Milad has dedicated over 25 years to the Medical Device Industry, with two decades at Boston Scientific. Before diving into his impressive tenure at Boston Scientific, we explore the earlier phases of his career and identify key turning points that shaped his professional journey. Milad provides insights into what his typical day at Boston Scientific looks like. We also discuss the competitive DBS landscape and how they create unique selling points for their program. Milad shares exciting developments and future plans that are on the roadmap, giving us a glimpse into the innovations driving the industry forward. Finally, we illuminate Boston Scientific's approach to DBS with their unique strategy and focus on image guidance – among other concepts. Our conversation also addresses the academic community's curiosity about transitioning to industry roles, with our guest presenting a compelling case for why a career in the medical device industry can be rewarding. Join us as we explore and map some new potential horizons for neuromodulation.

In this episode, we have an insightful conversation with Dr. Ali Rezai, who is the Associate Dean of Neuroscience at West Virginia University (WVU) and Executive Chair and Director of its Rockefeller Neuroscience Institute (RNI). We take a deeper dive into Dr. Rezai’s career, which features his notable achievement of performing 900 neurostimulator implants by 2006. We highlight Dr. Rezai’s involvement in deep brain stimulation (DBS) and focused ultrasound (FUS), particularly in treating severe traumatic brain injury and addiction. This episode features interesting findings on the sustained effects of low-intensity FUS in addiction, as well as the possibilities of opening the blood-brain barrier for the treatment of Alzheimer’s disease. Dr. Rezai shares more about RNI’s core mission and his leadership experiences in various medical societies, namely CNS, NANS, and ASSFN. We also discuss anecdotes from his presentations to various politicians, including President George W. Bush. We cover a lot of ground in this episode, and it truly offers a comprehensive look into Dr. Rezai’s remarkable contributions to neuroscience and the broader medical field.

Mallory Hacker is an Assistant Professor for Neurology in the team of David Charles, who is Professor of Neurology, Vice-Chair for Business Development and Strategy, as well as the Medical Director for Telehealth at Vanderbilt University Medical Center in Nashville, Tennessee. In 2006, after a stay at Alim Louis Benabids team in Grenoble, France, David started to investigate the question of whether subthalamic DBS could lead to slowing of motor progression in patients with early stages of Parkinson’s Disease. In a one-of-a kind trial, he collected data on the first patients which were published in 2014.In subsequent follow up trials, many of which were first-authored by Mallory Hacker, Class II evidence that supports this hypothesis could be established. It was a great joy to host Mallory in my lab in Berlin in 2022 and we have looked at the effects of lead locations on patients enrolled in the pilot trial. This is what convinced me that there might be something: The few patients that did not progress at all in their motor symptoms after two years were all precisely stimulated at the optimal location within the STN, while the ones that did progress, were more off target. Indeed, these same optimally placed patients had lower stimulation amplitudes and received less medication – but still had a clearly better outcome. Since the original trial, David and Mallory have been hard at work in trying to secure funding for a phase III pivotal trial, and we discuss how difficult this process has been, but also, that there is hope on the horizon, regarding the next steps!

Harith Akram is the consultant neurosurgeon at the National Hospital for Neurology and Neurosurgery (UCLH) and the Unit of Functional Neurosurgery (UCL) at Queen Square. We discuss Dr. Akram's hobbies beyond the lab and OR and delve into his fascinating journey which culminated in him training in the UK, with many stops along the way. Harith shares insights into his illustrious career, highlighting the key mentors who shaped his path, including Drs. Marwan Hariz and Ludvic Zrinzo. With many anecdotes about these influential figures, he reveals the unique lessons each imparted on his training. We then explore Harith's research and clinical work, from the creation of the innovative 'Gilgamesh' to his highly cited STN symptom-specific sweetspots paper. He discusses the practical impacts of his research on surgical practices and his involvement in pivotal projects like the four-lead OCD trial and thalamic segmentations based on tractography. The conversation also touches on underutilized therapies, such as DBS for cluster headaches, and the exciting potential of a new MR sequence he designed (i.e., FAT1). Harith provides his perspective on the future of lesion-based therapies, particularly cingulotomies for OCD and pain. Harith shares his advice for young researchers, reflects on missed opportunities, and engages in rapid-fire questions that reveal his thoughts on the future of neuroscience and academia. Join us for an inspiring and informative episode that showcases Harith's remarkable journey and contributions.