Neurosalience

Randy McIntosh, Ph.D. has been a scientist at the Rotman Research Institute of Baycrest Centre at the University of Toronto since 1994 and, since the start of 2022, is the new Director of the Simon Fraser University Institute for Neuroscience and Neurotechnology in Burnaby British Columbia - just outside of Vancouver. Randy obtained his PhD in 1992 from the University of Texas at Austin in Psychology and Neuroscience and did a postdoc at the NIH with Barry Horwitz until 1994. His group uses neuroimaging and computational modeling to understand the dynamics of healthy brains as well as those from many different clinical populations, lending insight and providing potential biomarkers through comparing his dynamic brain models with empirical data. He is also part an international consortium called the TheVirtualBrain which is an open science neuroinformatics platform for modeling the brain. Along with the exciting news of Randy’s new position, he has also just published a two part book called A Complex Journey - which is a sci-fi novel that delves into the complexity of the brain. Discussion: In this discussion we talk about his research in modeling brain dynamics, and specifically about this ambitious yet increasingly impactful project involving The Virtual Brain. We also delve into the different kinds of brain modeling approaches and what these different models provide. Lastly we talk about his new position as well as his new institute’s unique goals of more effectively translating neuroscience to all inclusive clinical care for individuals.

Today we are discussing the general question of how neuroimaging (and mostly fMRI) fit into the landscape of neuroscience research approaches. More specifically we discuss the question of what, over the years, has neuroimaging taught us about the brain? In this fascinating discussion, we work through many related topics and get a solid sense of Dr. Passingham’s perspectives on these - including his views on mentoring, a critique or refinement of David Marr’s three criteria for understanding the brain, the need to put forth falsifiable hypotheses, his enthusiasm for for Optically Pumped Magnetometers, and the need for an array of tools and approaches - not just fMRI -  for understanding the brain. Guest: Dick Passingham, Ph.D. is currently Emeritus Professor of Cognitive Neuroscience at the Department of Experimental Psychology, University of Oxford, and is also an Emeritus Fellow of Wadham College, Oxford. In addition, he is Emeritus Honorary Principal Investigator at the Wellcome Centre for Human Neuroimaging at University College London.  His career has been spent at these two institutions, and from 1991–1995 also at the MRC Cyclotron Unit at the Hammersmith Hospital London. He has published over 200 research papers and eight books. Lastly, he was elected a Fellow of the Royal Society in 2009 in recognition of his achievements.

In this episode Dr Peter Bandettini and co-host Dr Brendan Ritchie interview Dr Grace Lindsay. They find out about her new book 'Models of the mind' and about the process of writing a book. In doing so, they consider different types of brain models, from simply descriptive to more mechanistic, from too simple to overfitted. They describe the challenge in neuroscience of network modelling - the many unknowns and limited data and how output of the model may help inform its accuracy. They then discuss specific models, such as Deep Neural Networks, and how this type of modelling may progress in the future. Last, Lindsay gives some thoughts about the future hopes, philosophies, and strategies of modelling - how doing it well is both an art and a science.

Pedro Valdes-Sosa, an expert in EEG analysis, discusses his early career, creative work in EEG signal interpretation, his visiting position in Chengdu, China, the growing EEG database, and his international consortium. He briefly touches on medical care in Cuba and Cuba's response to COVID-19. They also explore topics such as universal screening for hearing loss, challenges in source analysis for EEG and MEG, intelligence and brain structure in Latin America, sharing multinational EEG data, integrating science and public health, COVID-19 longitudinal study and brain-induced disorders, the impact of the pandemic on science inequity, and challenges and optimism in spreading science.

Peter talks to Dr. Lucina Uddin about the constant struggle shared by all scientists in the field of neuroimaging to find the right paradigms, acquisition tools, and analysis approaches to add insight into fundamentals of brain organization and how it relates to behavior. They talk about cognitive flexibility, Autism, the salience network, and the need for an ontology of network nomenclature so that the field can better communicate, share, and understand findings. They also discuss the NIH’s goal of having a research domain criteria (RDoC) to organize and understand disorders in a more brain data-driven manner. Lastly, they discuss her perspective on advancing diversity in science. It was a fun conversation that put in perspective the many challenges facing functional brain imaging research. Guest: Lucina Uddin received her B.S. in 2001 in Neuroscience and her Ph.D in Psychology/Cognitive Neuroscience, both from UCLA. From 2006 to 2008 she did a postdoc at NYU School of Medicine and from 2008 to 2010 performed a second postdoc at Stanford Cognitive and Systems Neuroscience Laboratory. From 2010 to 2013 she was an instructor in the Stanford School of Medicine, Department of Psychiatry and Behavioral Science. In 2014 she moved to the University of Miami and in 2018 became, as an Associate Professor, the Director of Cognitive and Behavioral Neuroscience Division. She is a Handling Editor of the journal NeuroImage and Senior Editor of the journal Network Neuroscience. She’s written two books, “Insula” in 2014 and “Salience Network of the Human Brain” in 2016. She won the OHBM young investigator award in 2017 and the OHBM diversity award in 2021. Over the past 15 years, Lucina has rapidly risen in the ranks of respected cognitive neuroscientists who effectively and creatively use cutting edge MRI and fMRI. She and her lab investigate the relationship between brain connectivity and cognition in typical and atypical development, welding the tools of functional connectivity analyses of resting-state functional magnetic resonance imaging data as well as structural connectivity analyses of diffusion-weighted imaging data. For more info on the Neurosalience podcast and the guests, visit ohbmbrainmappingblog.com

Functional MRI is a profoundly successful and powerful technique that so many of us use. It’s still developing and adding to our insight about the human brain. While MRI was developed in the late 1970’s and early 80’s, it would be another decade before it was realized that MRI could be used to detect and map, non-invasively, human brain activation. My guests today, Ken Kwong, Bob Turner, and Ravi Menon were the first who showed this capability. Ken’s successful experiment in early May of 1991 was arguably the first. Ravi, who was the key player in the Minnesota group, had produced solid fMRI results by the summer of 1991, and I had my first successful experiment in Sept of 1991. Bob Turner was a key player in his physiologic manipulation experiments in Cats. He collaborated with Ken, and also showed results of his own at 4T shortly after as well. We were all there at the Society for Magnetic Resonance Imaging Meeting in San Francisco in August of 1991 when Tom Brady (who headed MGH NMR Center at the time), first showed in his plenary lecture, the crude but stunning jaw dropping brain activation movies. The moment I saw that, I knew what I wanted to do for the rest of my career. We have them all here to reflect on those heady days, what led up to their findings, and the bright future of fMRI. Guests: Ken Kwong has been conducting MRI research at the Mass General Hospital since the late 80’s when he pioneered diffusion imaging, as well as perfusion imaging approaches. He’s currently associate professor at the MGH Martinos Center. Robert Turner trained with inventor of Echo Planar Imaging, Peter Mansfield, among others, and while working at the NIH, performed those first critical experiments, demonstrating BOLD contrast as well as obtaining some of the first results in humans at 4T using his home built gradient coil. One of Bob’s major contributions to the field was his early work in gradient coil design - which remains fundamental to what we do. From 2006 to 2014 he was the Director of the Department of Neurophysics at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig and is currently retired and living in Cambridge, England. Ravi Menon was a post doc at Minnesota and a driving force in the effort to produce functional images using a highly challenging non-EPI approach at 4T. He has been a steady contributor to fMRI methods ever since and is currently a Robarts Scientist and Canada Research Chair in Functional Magnetic Resonance Imaging, Co-Scientific Director of BrainsCAN which is Canada First Research Excellence Fund, Scientific Director, Centre for Functional and Metabolic Mapping, and Professor of Medical Biophysics, Medical Imaging & Psychiatry at The University of Western Ontario

Maurizio Corbetta is Full Professor and Chair of Neurology in the Department of Neuroscience at the University of Padua, Italy. He is also the founding director of the new Padua Neuroscience Center, a highly interdisciplinary research programme centered on the idea of brain networks in health and society. After receiving is M.D. from the University of Pavia in Italy, he carried out a residency in Neurology at the University of Verona. In 1990 he moved to US, carting out a fellowship in NeuroImaging at Barnes Hospital at Wash U in St. Louis. While in St. Louis, he worked his way up to being the Norman J. Strupp Professor of Neurology, and Professor of Radiology, Anatomy, Neurobiology Bioengineering and Neuroscience at Wash University, as well as Director of Stroke and Brain Injury Rehabilitation at the Rehabilitation Institute of St. Louis. He moved back to Italy, to teh University of Padua, in 2016. Prof. Corbetta has pioneered experiments on the neural mechanisms of human attention using Positron Emission Tomography (PET). He has discovered two brain networks dedicated to attention control, the dorsal and ventral attention networks, and developed a brain model of attention. His clinical work has focused on the physiological correlates of focal injury. He has developed a pathogenetic model of the syndrome of hemispatial neglect. He is currently developing novel methods for studying the functional organization of the brain using functional connectivity MRI, magneto-encephalography (MEG), and electro-corticography (EcoG). He is also working on the effects of focal injuries on the network organization of brain systems with an eye to neuromodulation. He is known for the high level of rigor and deep insight of his research, and has over 16 papers with over 1000 citations. Discussion In our conversation, we discuss some of the key people that influenced him, the incredible team of people at Washington University, as well as some of his early work. We also discuss his perspective on the utility and information in resting state fMRI. He’s senior author of one of the most provocative and compelling explanations for resting state activity that I’ve seen: titled The secret life of predictive brains: what’s spontaneous activity for? Pezzulo et al TICS 2021. We go on from there to discuss his perspective of the substantial importance and profound potential of systems level neuroimaging to not only basic neuroscience but also to clinical practice. Toward the end of our discussion, he highlights how diagnosis and treatment of stroke with neuromodulation can leverage current state of the art neuroimaging techniques.

Guest: Anastasia Yendiki is a faculty member at the MGH Martinos center and a member of the Laboratory for Computational Neuroimaging (LCN).  Her background is in statistical signal and image processing. She received her Ph.D. in Electrical Engineering from the University of Michigan at Ann Arbor, where she worked on inverse problems in tomographic reconstruction for nuclear imaging. As a postdoctoral research fellow at the Martinos Center, Harvard Medical School and Massachusetts General Hospital, she trained in functional and diffusion-weighted MRI. She is responsible for the development of the diffusion MRI analysis tools in FreeSurfer, including TRACULA (TRActs Constrained by UnderLying Anatomy), a diffusion-weighed MRI analysis stream in Bruce Fischl’s FreeSurfer, for automatically reconstructing a set of major white matter pathways from diffusion MRI data using global probabilistic tractography with anatomical priors. She is also interested in ex vivo imaging of human brain circuits with diffusion MRI and optical imaging to both validate and train algorithms for in vivo tractography. Discussion In this wide-reaching discussion we delve into all aspects of her work developing diffusion-based tractography, including her work on better algorithms, current unknowns and challenges, her validation studies, clinical applications, and Connectome scanner at MGH. Towards the end we discuss the planned connectome II scanner and some of the most exciting challenges the field faces.

Denis LeBihan, M.D., Ph.D., is a clinician and physicist, a relentless innovator in the field of MRI and fMRI since the late 80’s, and—as we hear in this podcast—a broad, deep, and highly creative thinker who remains passionate about his work. Denis is the founding director of NeuroSpin in Orsay, France and spends time in Japan as a guest professor at the University of Kyoto and National Institutes of Physical Sciences in Okazaki.   Denis Le Bihan has achieved international recognition for his truly fundamental contributions to the development of diffusion MRI, diffusion tensor imaging (DTI), and the concept of IVIM to image perfusion. It is the b in his name from which the ubiquitous b-factor in diffusion comes from. He has more recently demonstrated the ability to image brain activation-related diffusion coefficient changes. In this podcast, we discuss the intellectual history of Denis’ career. He produced the first diffusion-weighted images, helped establish diffusion tensor imaging, and advanced the concept of imaging perfusion as having an “apparent diffusion coefficient” (ADC) and order of magnitude higher than water diffusion. He has also demonstrated that water diffusion, when imaged with very high b-values, decreases with brain activation. Cell swelling increases the surface area of cells where low diffusion coefficient water resides, thus lowering overall diffusion coefficient. This last result is still debated but generally gaining acceptance with each new paper demonstrating the effect. He also spends some time in the episode talking about his foray into modeling brain function, tapping into inspiration from Einstein and relativity. Overall, it was a fun and inspiring conversation!

In this episode Peter Bandettini speaks with the Chairs of three large neuroimaging societies: Randy Gollub from the Organization for Human Brain Mapping (OHBM), Fernando Calamante from the International Society for Magnetic Resonance in Medicine (ISMRM) and Ron Mangun from the Cognitive Neuroscience Society. Together they consider how COVID-19 has impacted the annual meetings of these societies and some of the innovative strategies used to increase interactivity at online or hybrid meetings.  For more info on the Neurosalience podcast and the guests, visit: www.ohbmbrainmappingblog.com