#56: Harith Akram – Connectomic DBS, Sweetspots and Building a Supercomputer

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.

Jens Volkmann is a Professor and the chair of Neurology at University Hospital Würzburg in Germany and one of the key DBS experts in the field. I have intensely collaborated with Jens and his team and he has been a mentor for me since a long time. In fact, in this conversation, Jens reminded me of exactly when we first met, during a summer school in cortona, italy, where I was fortunate enough to listen to fantastic talks by exciting faculty including Jens about the future of Deep Brain Stimulation. Jens has been a pioneer of image guided DBS and has come up with fantastic concepts and models around the mechanism of action of DBS. He has also largely contributed to advancing the fields based on clinical studies and is very broadly informed about the past, present and future of the field in both human and animal work around the technology. I hope you enjoy this conversation as much as I did, and thank you for tuning into Stimulating Brains!

  Phil Starr is a Professor of Neurological Surgery at University of California, San Francisco and a developer of implantable brain devices. At UCSF, he co-directs a multidisciplinary neurology/neurosurgery movement disorders clinic together with Dr. Jill Ostrem. I’ve been a long-time admirer of Phil’s work and in this conversation we blaze through quite a few of his numerous publications. One key breakthrough and invention of Phils work has been to include Ecog recordings – both intraoperatively but also chronically – to investigate brain signals in various states. We talk about the Open Mind Consortium, Mentorship and the cross-pollination between academia and industry. One key highlight of Phils work is a paper which was accepted for publication in Nature Medicine, at the time of recording this just yesterday. In it, the three co-first authors Carina Oehrn, Stephanie Cernera and Lauren Hammer demonstrate the chronic use of a newly identified cortical physiomarker, which is now referred to as the finely tuned gamma activity. I hope you enjoy this conversation as much as I did, and thank you for tuning into Stimulating Brains!

Dr. Mark Hallett is arguably the person that put transcranial magnetic stimulation (TMS) on the map. Besides that, he is an authority in the field of movement disorders and motor control, with specific focus – spread throughout the years – on Parkinson's Disease, dystonia and functional movement disorders. In our conversation, Dr. Hallett shares anecdotes from the early time of the TMS field, his large number of mentors and even larger number of mentees, how he was able to treat the pianist Leon Fleisher with botolinum toxin, the enigmatic pathomechanism of dystonia, the mysterious cases of the Havanna syndrome, and his work with functional neurological disorders. We include guest questions by none less than Drs. Mark S. George, Mike D. Fox, Christos Ganos, Robert Chen, Joseph Claßen, Shan Siddiqi and Joseph Taylor. Dr. Hallett is an NIH Distinguished Investigator and the Chief of the Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda. He trained at Harvard Medical School, NIH, Massachusetts General Hospital and the Institute of Psychiatry in London. He is past President of the International Federation of Clinical Neurophysiology and the President of the newly founded Functional Neurological Disorder Society. Dr. Hallett is also remote past President of the Movement Disorder Society and past Editor-in-Chief of Clinical Neurophysiology. He has won many awards including, in October 2019, the World Federation of Neurology Medal for Contributions to Neuroscience. His work mainly deals with principles of motor control and the pathophysiology of movement disorders. He authored >1,200 scientific papers with more than 160,000 citations and has an H-index of 212. According to research.com, Dr. Hallett is the 75th most cited researcher in the US, and 104th in the world.

In our ongoing exploration of the DBS ecosystem through the lens of key industry leaders, below is our conversaion with Amaza Reitmeier who is the Vice President and General Manager of Brain Modulation at Medtronic. We learn differences between life in academia and industry, with a key potential of industry work to get the ability to make change at scale. In this episode, we discuss what the future of brain modulation may offer, with some aspirational commentary on several potential opportunities for DBS and related therapies. Some of the opportunities we discuss are currently under development by Medtronic or others, while other opportunities may still be in a nascent state without a concrete roadmap for incorporation into a particular product or therapy.