Podcasts about montreal neurological institute

In this episode, we journey through the remarkable career of Dr. Rees Cosgrove—a trailblazer in functional neurosurgery, Director of Epilepsy and Functional Neurosurgery at Brigham and Women's Hospital, and Professor of Neurosurgery at Harvard Medical School.Dr. Cosgrove reflects on his formative years training in the very halls that were roamed by legends such as Wilder Penfield at the Montreal Neurological Institute, and takes us through pivotal chapters of his career leading programs at Massachusetts General Hospital, Brown University, and now the Brigham. With a repertoire that spans from the golden era of ablative neurosurgery to modern deep brain stimulation and MR-guided focused ultrasound—where he has performed over 600 sonications—Dr. Cosgrove provides a unique perspective on how the field has transformed over the past several decades.Throughout the conversation, we delve into the history and resurgence of surgical lesions for psychiatric and neurological conditions, the nuances of neuromodulation technologies, and the evolution of imaging that now defines precision in brain surgery. Dr. Cosgrove also shares his views on mentorship, the transmission of surgical wisdom, and how we can preserve the disappearing art of lesioning in an age increasingly dominated by stimulation.Whether you're a neurosurgeon, neuroscientist, or simply curious about how we interface with the brain to treat disease, this episode is a rare and insightful look into the mind of one of the field's most experienced and thoughtful pioneers.

Christian Drapeau, MSc. is a neurophysiology scientist and leading voice on stem cells who focuses on discovering and developing ways to naturally enhance human stem cell production, mostly through plant extracts that stimulate the body's own stem cell production. He was the first to propose and publish the hypothesis that stem cells constitute the "repair system" of the body, as published in his peer-reviewed Medical Hypotheses article in October 2002 and documented in the first edition of his breakthrough book Cracking the Stem Cell Code in 2010. These findings made him the first to name a new bodily system since the early 1900s. Owning nine patents related to stem cells, he has spent over 23 years conducting research to better understand the role they play and identifying ways to improve the performance of the body's repair system, the foundation of regenerative medicine. Christian Drapeau holds a degree in neurophysiology from the Montreal Neurological Institute in Montreal, Canada. He has given over 300 scientific lectures on stem cells in 51 countries, and is fluent in three languages. He has been Director of R&D and Chief Science Officer for a number of companies, including his most recent venture STEMREGEN, where he is Founder and Chief Science Officer and continues his work of researching and developing novel stem cell enhancers.  In this episode, Christian Drapeau gives us the stem cell basics, discusses their effectiveness and why boosting your own stem cells is a good idea.  Learn more about Christian Drapeau and get StemRegen products here: https://stemregen.co/coachtara  Instagram: @stemcellchristian Get 15% off Peluva minimalist shoe with coupon code COACHTARA here: https://peluva.com/ CHAPTERS 0:00 Intro 4:50 Stem cells basics 17:21 StemRegen results 23:36 Effectiveness 31:58 Heart disease 38:48 Aging

https://renegadehealthboss.com In episode 126, Heather Gray FDN-P welcomes Christian Drapeau, a leading expert in stem cell research. Christian shares his fascinating journey from studying blue-green algae at Klamath Lake to discovering the role of stem cells as the body's natural repair system. The discussion covers the groundbreaking implications of plant-based stem cell stimulation, Lyme disease, and the potential of algae in healing. In this podcast you will discover 00:00 Introduction to the podcast and guest Christian Drapeau, a leader in stem cell research. 01:24 Christian discusses his background in brain research and how his studies on blue-green algae led to the discovery of stem cells 05:18 Significance of stem cells and how they can transform into various types of cells within the body. 07:06 Christian and his team identified that blue-green algae could trigger the release of stem cells from the bone marrow. 08:11 Heather and Christian touch on the current buzz around stem cells and the controversies surrounding them. 08:32 Christian shares an intriguing story about Lyme disease research and the mysterious "boogers" discovered in blood samples 11:21 Discussion on blue-green algae may suppress these harmful microorganisms and its broader implications for health. 14:02 Introduction to the importance of a holistic approach in managing chronic illnesses and the role of biological medicine. 15:25 Discussion on the pioneering work of Dave Asprey and the significance of blue-green algae in stem cell activation. 17:10 Development behind using specific plants to trigger the release of stem cells, 18:42 Exploration of the unique environment of Klamath Lake, where the blue-green algae thrive 22:07 Remarkable recoveries from severe conditions such as heart disease and Parkinson's 24:25 Ongoing clinical trials and the promising future of stem cell treatments for various chronic illnesses. 27:58 Find more information about stem cell research and how to start your own journey toward better health. To Get BioMed: Contact Dr. Drobot here https://thebiomedcenter.com/ Tel:480-614-5820 Only contact the Scottsdale location To get CAROL Bike Click here https://carolbike.com/ use code RHB to get $100 off The CAROL Bike offers a 100-day return policy. A full refund, buy with confidence. Guest Bio: Christian Drapeau, MSc, is a neurophysiologist and pioneer in stem cell research, known for his work on enhancing natural stem cell production through plant extracts. He proposed the groundbreaking hypothesis that stem cells form the body's "repair system," published in 2002. With nine patents and over 23 years of research, he has made significant contributions to regenerative medicine. Drapeau holds a degree from the Montreal Neurological Institute and has lectured in 51 countries. He is the Founder and Chief Science Officer of STEMREGEN To learn more about Christian Drapeau: www.stemregen.co/RHB Get healthier food into your diet with these easy, yummy, fast meals today! Get more energy, less brain fog, and LESS pain when you start eating a low-inflammatory diet Download your free video series Real Cooking For Real Life here. https://renegadehealthboss.com/real-cooking-for-real-life-recipe-book/ #RenegadeHealthBoss #StemCells #RegenerativeMedicine #Neurophysiology #HealthInnovation #StemCellTherapy #youarenotcrazy #PlantBasedHealing #MedicalBreakthrough #itsnotinyourhead #HealthTech #StemCellResearch #CellularHealth #StemCellEnhancement #thelymeboss #thereishope #ScienceAndHealth --- Support this podcast: https://podcasters.spotify.com/pod/show/renegadehealthboss/support

I'm excited to share a special episode of the Wealthy Wellthy Podcast that dives deep into the world of stem cells and their potential for health and healing. In this episode, I had the pleasure of interviewing my friend, Christian Drapeau, a scientist whose journey is as unique as his discoveries. We were introduced through a mutual friend, Lynn Graft, and it's been a meaningful friendship ever since. Christian's background is anything but ordinary – from studying neurophysiology at the Montreal Neurological Institute to living in a monastery, his path has been a quest for deeper understanding and truth. During our conversation, Christian shared his transition into the world of stem cell research, which began with his study of a blue-green algae from Klamath Lake. His discovery that this algae acts as a stem cell mobilizer set the stage for his life's work. One of the most compelling parts of our discussion was Christian's personal story of healing and transformation. After a serious health scare that left me on five different prescriptions, I realized I needed a different approach to take control of my health. Christian's insights into natural healing and the body's innate ability to repair itself through stem cell mobilization resonated deeply with me. He explained how traditional medicine often focuses on treating symptoms rather than addressing the root cause, and how stem cell therapy offers a more holistic solution. Now, Christian is at the forefront of research into plant-based stem cell mobilizers, showing how these natural compounds can stimulate the body's repair systems. His work has led to real-life stories of healing, from reversing chronic diseases to repairing severe injuries. Listening to Christian, it's clear that his belief in the power of plants and natural healing is backed by rigorous science and a profound understanding of the body's potential.

Embark on a scientific journey in this episode of the Align Podcast as we delve into the fascinating world of stem cells with renowned neurophysiology scientist, Christian Drapeau. With over two decades of research, Christian brings to light the origins of stem cells, the potential of plant extracts in enhancing stem cell regeneration, the risks associated with exogenous stem cells, and the latest findings in longevity research. In this detailed discussion, Christian explains the different types of stem cells, their sources, and how cutting-edge science is utilizing plant-based extracts to promote the body's natural regenerative capabilities. He also addresses the ethical considerations and potential risks involved in stem cell therapy, providing a balanced view on this groundbreaking area of science. This episode is a must-watch for anyone interested in the latest advancements in medical science, particularly in how stem cells can be harnessed to improve health and potentially extend life spans. More About Christian: Christian Drapeau, MSc. is a neurophysiology scientist and leading voice on stem cells who focuses on discovering and developing ways to enhance human production of stem cells naturally, mostly through plant extracts that stimulate the body's own stem cell production. He was the first to propose and publish the hypothesis that stem cells constitute the "repair system" of the body, as published in his peer-reviewed Medical Hypotheses article in October 2002, and documented in the first edition of his breakthrough book Cracking the Stem Cell Code in 2010. These findings made him the first to name a new bodily system since the early 1900s. Owning multiple patents related to stem cells, he has spent over 23 years conducting research to better understand the role they play in the human body and identifying ways to improve the performance of the body's repair system, the foundation of regenerative medicine. Christian Drapeau holds a degree in neurophysiology from the Montreal Neurological Institute in Montreal, Canada. He has given over 300 scientific lectures on stem cells in 51 countries, and is fluent in three languages. He has been Director of R&D and Chief Science Officer for a number of companies, including his most recent venture STEMREGEN, where he is Founder and CEO and continues his work of researching and developing novel stem cell enhancers. He has 700,000 followers on TikTok (@StemCellChristian) where he discusses a variety of wellness topics and educates about stem cells. Where To Find Christian: Christian's Website TikTok: @StemCellChristian Instagram: @StemCellChristian STEMREGEN: https://www.stemregen.co/ Biohacking Conference: https://www.biohackingconference.com/ Thank You To Our Sponsors: Stemregen is a supplement that contains plant extracts that have been scientifically documented to trigger the release of more stem cells from the bone marrow, supporting everything from healthy aging and athletic recovery - to cellular rejuvenation from within.  To learn more about this breakthrough supplement, go to Stemregen.co. - Experience the Sunlighten Infrared Saunas for yourself! CLICK HERE and use code “ALIGN” when you fill out the Get Pricing form to save up to $600 on your purchase! -

Christian Drapeau is a pioneer in Adult Stem Cell research and has attained global recognition for his nutraceutical applications in the fields of regenerative medicine and wellness. Christian Drapeau holds a degree in Neurophysiology from the Montreal Neurological Institute, affiliated with McGill University in Montreal, Canada. He has been the Chief Science Officer for Cell Tech, Desert Lake Technologies, and Stemtech International.He is currently a member of the Scientific Advisory Board for Jeunesse Global and the President/CEO of Kalyagen where he continues his work of Research & Development, investigating novel stem cell enhancers.

If you are interested in working with Nathan, he is currently recruiting for a postdoc! Send your CV to lbc.spreng@gmail.com Today our guest is Nathan Spreng. Dr. Spreng is the James McGill Professor of Neurology and Neurosurgery and Director of the Laboratory of Brain and Cognition at the Montreal Neurological Institute and Hospital at McGill University. As an undergraduate, Dr. Spreng was initially interested in pursuing a major in poetry until he took a psychology class that sparked his interest in the brain. He received Ph.D. in 2008 from the University of Toronto in Brian Levine's lab, and post docs with Cheryl Grady at the University of Toronto and Dan Schacter at Harvard. After about 5 years as an assistant professor at Cornell University, he moved to McGill University. Throughout his career Dr. Spreng has been using fMRI to reveal subtle yet repeatable large-scale brain networks as they relate attention, memory, cognitive control, and social cognition. He has also helped to elucidate the central role that the default network plays in self-generated thought, and in how it dynamically interacts with multiple systems in the brain. In this episode Peter and Nathan have a far reaching conversation about his work and what it implies, covering his study of age dependence of resting state hippocampal-linked network ensembles, how to move from mapping networks to modeling and understanding mechanisms, the many possible clinical implications of his work, current understanding of Alzheimer's disease, our mutual appreciation for multi-echo EPI, his data release paper of a large multi-echo EPI and structural MRI data set, and much more. Enjoy listening! Episode producers: Alfie Wearn Omer Faruk Gulban

Dr. Thomas Durcan is an Associate Professor and Director of the Early Drug Discovery Unit at the Montreal Neurological Institute. He oversees a team of 40+ research staff and students, committed to applying patient-derived stem cells towards the development of phenotypic discovery assays and 3D neuronal organoid models for neurodegenerative and neurodevelopmental disorders. He talks about modeling sporadic ALS in a dish, partnering with the Michael J. Fox Foundation, and promoting open science.

In this week episode Lisa interviews world renown stem cell scientist Dr Christian Drapeau on the power of stem cells to heal the body and how we can mobilise many more of these stems cells from our bone marrow through the use of specific botanicals that have been clinically shown to do just that and how people suffering from a myriad of disease all have one thing in common and that is low circulating levels of stem cells.   We dive into the fascinating world of stem cell science and you will learn:           * The types of stem cells there are         * The various use cases for the different stem cells         * The history of embryonic stem cells and adult stem cells.         * The botanical discoveries he made that have shown to mobilise your own stem cells without needing invasive procedures that harvest your own stem cells from bone marrow or fat         *Lifestyle interventions shown to improve stem cell mobilisation and other habits that are detrimental to your stem cell supply.         * we dive into many stories giving insight to the mechanisms of actions, case studies that are astounding from burns victims healing 50 year old scars to diabetics getting off insulin, to heart repair, brain repair and more.         * we dive too into the clinical research he and others have done   Dr Christian is the author of "Cracking the Stem Cell Code" and is a tireless advocate for sharing this powerful and world changing information. If after listening to this show you want to try STEMREGEN, Dr Christian's product you can go to and use code "Lisa" for a discount off your purchase and check back in Lisa's own anti-aging shop as she will soon have STEMREGEN  in stock at www.shop.lisatamati.com [1] Dr Drapeau says “Our health industry calls for a new paradigm… One where we exit the disease-based model of care and enter a model based on maintaining optimal health.  To fully embrace this new approach, we must first understand the process by which our body maintains health of its own accord.  Through years of research, we have discovered that adult stem cells are the building blocks of this process, and we have discovered plants capable of tapping into the healing potential of adult stem cells in order to support our highest potential for vibrant health.”   ~Christian Drapeau, MSc Stem Cell scientist Botanical researcher Author   Dr Christian Drapeau Bio Christian Drapeau is a pioneer in Adult Stem Cell research and has attained global recognition for his nutraceutical applications in the fields of regenerative medicine and wellness. Christian Drapeau holds a degree in Neurophysiology from the Montreal Neurological Institute, affiliated with McGill University in Montreal, Canada.  He has been the Chief Science Officer for Cell Tech, Desert Lake Technologies, and Stemtech International. He is currently a member of the Scientific Advisory Board for Jeunesse Global and the President/CEO of Kalyagen where he continues his work of Research & Development, investigating novel stem cell enhancers. The natural role of stem cells in the body as the foundation of the body's daily repair and tissue regeneration system was first described in Christian's book Cracking the Stem Cell Code (2010). A new edition was published in 2021 presenting all the data on plant-based stem cell enhancers, along with descriptions of cases showing remarkable recovery using natural stem cell enhancers to support Endogenous Stem Cell Mobilization (ESCM). Working on the aquatic botanical Aphanizomenon flos-aquae (AFA), in the late 1990's, and observing that consumption of AFA was leading to benefits touching many aspects of human health, Christian Drapeau proposed that bone marrow stem cells constitute the natural repair system of the body and that AFA's mechanism of action consisted in supporting stem cell release from the bone marrow. Work done later confirmed these two hypotheses. In essence, he has delineated how the bone marrow releases adult stem cells into the bloodstream to carry out the daily task of tissue repair within all bodily systems, and that the most important parameter in this natural ability to repair is the number of circulating stem cells. More stem cells in circulation has been linked to greater health, and conversely fewer circulating stem cells has been linked to disease formation. This finding has profound implications for every area of regenerative medicine, from disease treatment and prevention to anti-aging. He also discovered that the aquatic botanical AFA works in the body by stimulating stem cell mobilization (release) from the bone marrow. By increasing the number of circulating stem cells, more stem cells are available to participate to the process of tissue repair and renewal.   Health Optimisation and Life Coaching with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clincian with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis She can help you navigate the confusing world of health and medicine and can advocate for you. She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whether you are facing challenges from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out.: Consult with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialised range of exclusive longevity, health optimising supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her mum but couldn't get in NZ. Check out the range at her LongLifeLabs shop   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books My latest book Relentless chronicles the inspiring journey of how my mother and I defied the odds after an aneurysm left my mum, Isobel, with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: Lisa's Books   Our NMN Bio Flagship Longevity Range A range by molecular biologist Dr Elena Seranova NMN: Nicotinamide Mononucleotide, an NAD+ precursor Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, decreases dramatically over time.   What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health so you can live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and rigorously tested by an independent, third-party lab. Start your cellular rejuvenation journey today.   Support Your Healthy Aging We offer powerful third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now: NMNBIO NMN (beta Nicotinamide Mononucleotide) 250mg | 30 capsules NMN (beta Nicotinamide Mononucleotide) 500mg | 30 capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 250mg | 30 Capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 500mg | 30 Capsules Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health Metabolic Health Listen to the episodes with Dr Seranova on the show: https://www.lisatamati.com/podcast--dr-elena-seranova/ https://www.lisatamati.com/podcast--dr-elena-seranova-part-3/   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr MInkoff here:  Ketone Products by HVMN The world's best  exogenous Ketone IQ Listen to the episode with Dr Latt Mansor Lisa's  ‘Fierce' Sports Jewellery Collection For Lisa's gorgeous and inspiring sports jewellery collection, 'Fierce', go to Jewellery   For Vielight Device Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com Use code "tamati" at checkout to get a 10% discount on any of their devices.   Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa and team

Bidirectional links between epilepsy and sleep have been known for thousands of years. Despite nearly a century of research using EEG investigations, the relationships are still not well understood.Dr. Laurent Sheybani interviewed Dr. Birgit Frauscher, an epileptologist and sleep specialist at the Montreal Neurological Institute. They discussed what is known about sleep patterns, how sleep may influence epileptic activity and vice versa, and how sleep research may lead to more effective epilepsy treatments.Studies mentioned in the interview include:Interictal Hippocampal Spiking Influences the Occurrence of Hippocampal Sleep Spindles (Frauscher et al., 2015, Sleep)Focal epilepsy disrupts spindle structure and function (Schiller et al., 2022, Nature Scientific Reports)Origin and significance of the cyclic alternating pattern: Review article (Terzano & Parrino, 2000, Sleep Medicine Reviews)SleepSEEG: automatic sleep scoring using intracranial EEG recordings only (von Ellenrieder et al., 2022, J. Neural Eng.)Recurrent Hippocampo-neocortical sleep-state divergence in humans (Guthrie et al., 2022, PNAS)Scalp spindles are associated with widespread intracranial activity with unexpectedly low synchrony (Frauscher et al., 2015, Neuroimage)  The International League Against Epilepsy invites you to explore the ILAE Academy: Interactive, practice based online courses for health care professionals who diagnose and treat epilepsy. Find more information at ilae-academy.org. Support the showSharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Twitter, and Instagram.

Dr. Robert Goodman is a neurosurgeon at Hackensack University Medical Center and has been an innovator in the treatment of epilepsy for more than 30 years. He established one of the first multidisciplinary epilepsy centers in New York City. He is a scholar and has over 100 peer-reviewed publications to his name. After completing his medical education at Johns Hopkins University, he went on to complete his neurosurgery residency at New York Presbyterian - Columbia University Medical Center. He later completed his fellowship training in epilepsy surgery at the Montreal Neurological Institute. Today he is back on the show to talk about temporal lobe epilepsy.

Dr. Robert Goodman is a neurosurgeon at Hackensack University Medical Center and has been an innovator in the treatment of epilepsy for more than 30 years. He established one of the first multidisciplinary epilepsy centers in New York City. He is a scholar and has over 100 peer-reviewed publications to his name. After completing his medical education at Johns Hopkins University, he went on to complete his neurosurgery residency at New York Presbyterian - Columbia University Medical Center. He later completed his fellowship training in epilepsy surgery at the Montreal Neurological Institute. Today we are going to be speaking with Dr. Goodman about responsive neurostimulation (RNS) and deep brain stimulation (DBS).

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Blake Richards on Why he is Skeptical of Existential Risk from AI, published by Michaël Trazzi on June 14, 2022 on LessWrong. I have recently interviewed Blake Richards, an Assistant Professor in the Montreal Neurological Institute and the School of Computer Science at McGill University and a Core Faculty Member at MiLA. Below you will find some quotes summarizing his takes on AGI. Blake is not really concerned about existential risk from AI. Like Yann LeCun, he finds that AGI is not a coherent concept, and that it would be impossible for an AI to be truly general (even if we restrict the no free lunch theorem to economically valuable tasks). Why I Interviewed Blake Although I do not agree with everything he says, I think there is value in trying to interact with AI researchers outside of the AI Alignment bubble, understanding exactly what arguments they buy and do not buy, eventually nailing down some cruxes that would convince them that AI existential risk is worth thinking about. Better understanding LeCun's position has been valuable for many on LessWrong (see for instance the 2019 debate with Bengio and Russell), and Blake thinking is close to Yann's, given they are part of a similar philosophical bent. Why you Might Want to Talk to Skeptics Another exercise I found insightful was (mostly incorrectly) assessing people's views on AI Alignment and AI timelines, which made me understand better (thanks Cunningham's law!) the views of optimists (they turned out to be pretty close to Richard Ngo's reasons for optimism at 11:36 here). In any case, I recommend to people who are in touch with ML researchers or practitioners to 1) get to a level where they feel comfortable steelmanning them 2) do a write-up of their positions on LW/EAF. That would help nail down the community's understanding of what arguments are convincing or not, and what would make them change their mind. To that end, here are what Blake has to say about his position on AGI and what could make his change his mind about existential risk. Generalizing to "All Sort of Tasks We Might Want It To do" "We know from the no free lunch theorem that you cannot have a learning algorithm that outperforms all other learning algorithms across all tasks. [...] Because the set of all possible tasks will include some really bizarre stuff that we certainly don't need our AI systems to do. And in that case, we can ask, “Well, might there be a system that is good at all the sorts of tasks that we might want it to do?” Here, we don't have a mathematical proof, but again, I suspect Yann's intuition is similar to mine, which is that you could have systems that are good at a remarkably wide range of things, but it's not going to cover everything you could possibly hope to do with AI or want to do with AI." Contra Transfer Learning from Scaling "What's happened with scaling laws is that we've seen really impressive ability to transfer to related tasks. So if you train a large language model, it can transfer to a whole bunch of language-related stuff, very impressively. And there's been some funny work that shows that it can even transfer to some out-of-domain stuff a bit, but there hasn't been any convincing demonstration that it transfers to anything you want. And in fact, I think that the recent paper. The Gato paper from DeepMind actually shows, if you look at their data, that they're still getting better transfer effects if you train in domain than if you train across all possible tasks." On Recursive Self-Improvement "Per this specificity argument, my intuition is that an AI that is good at writing AI code might not have other types of intelligence. And so this is where I'm less concerned about the singularity because if I have an AI system that's really good at coding, I'm not convinced that it's going to be good at other...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Blake Richards on Why he is Skeptical of Existential Risk from AI, published by mtrazzi on June 14, 2022 on The Effective Altruism Forum. (crossposted from LW) I have recently interviewed Blake Richards, an Assistant Professor in the Montreal Neurological Institute and the School of Computer Science at McGill University and a Core Faculty Member at MiLA. Below you will find some quotes summarizing his takes on AGI. Blake is not really concerned about existential risk from AI. Like Yann LeCun, he finds that AGI is not a coherent concept, and that it would be impossible for an AI to be truly general (even if we restrict the no free lunch theorem to economically valuable tasks). Why I Interviewed Blake Although I do not agree with everything he says, I think there is value in trying to interact with AI researchers outside of the AI Alignment bubble, understanding exactly what arguments they buy and do not buy, eventually nailing down some cruxes that would convince them that AI existential risk is worth thinking about. Better understanding LeCun's position has been valuable for many on LessWrong (see for instance the 2019 debate with Bengio and Russell), and Blake thinking is close to Yann's, given they are part of a similar philosophical bent. Why you Might Want to Talk to Skeptics Another exercise I found insightful was (mostly incorrectly) assessing people's views on AI Alignment and AI timelines, which made me understand better (thanks Cunningham's law!) the views of optimists (they turned out to be pretty close to Richard Ngo's reasons for optimism at 11:36 here). In any case, I recommend to people who are in touch with ML researchers or practitioners to 1) get to a level where they feel comfortable steelmanning them 2) do a write-up of their positions on LW/EAF. That would help nail down the community's understanding of what arguments are convincing or not, and what would make them change their mind. To that end, here are what Blake has to say about his position on AGI and what could make his change his mind about existential risk. Generalizing to "All Sort of Tasks We Might Want It To do" "We know from the no free lunch theorem that you cannot have a learning algorithm that outperforms all other learning algorithms across all tasks. [...] Because the set of all possible tasks will include some really bizarre stuff that we certainly don't need our AI systems to do. And in that case, we can ask, “Well, might there be a system that is good at all the sorts of tasks that we might want it to do?” Here, we don't have a mathematical proof, but again, I suspect Yann's intuition is similar to mine, which is that you could have systems that are good at a remarkably wide range of things, but it's not going to cover everything you could possibly hope to do with AI or want to do with AI." Contra Transfer Learning from Scaling "What's happened with scaling laws is that we've seen really impressive ability to transfer to related tasks. So if you train a large language model, it can transfer to a whole bunch of language-related stuff, very impressively. And there's been some funny work that shows that it can even transfer to some out-of-domain stuff a bit, but there hasn't been any convincing demonstration that it transfers to anything you want. And in fact, I think that the recent paper. The Gato paper from DeepMind actually shows, if you look at their data, that they're still getting better transfer effects if you train in domain than if you train across all possible tasks." On Recursive Self-Improvement "Per this specificity argument, my intuition is that an AI that is good at writing AI code might not have other types of intelligence. And so this is where I'm less concerned about the singularity because if I have an AI system that's really good at coding, I'm not convinced t...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Blake Richards on Why he is Skeptical of Existential Risk from AI, published by Michaël Trazzi on June 14, 2022 on LessWrong. I have recently interviewed Blake Richards, an Assistant Professor in the Montreal Neurological Institute and the School of Computer Science at McGill University and a Core Faculty Member at MiLA. Below you will find some quotes summarizing his takes on AGI. Blake is not really concerned about existential risk from AI. Like Yann LeCun, he finds that AGI is not a coherent concept, and that it would be impossible for an AI to be truly general (even if we restrict the no free lunch theorem to economically valuable tasks). Why I Interviewed Blake Although I do not agree with everything he says, I think there is value in trying to interact with AI researchers outside of the AI Alignment bubble, understanding exactly what arguments they buy and do not buy, eventually nailing down some cruxes that would convince them that AI existential risk is worth thinking about. Better understanding LeCun's position has been valuable for many on LessWrong (see for instance the 2019 debate with Bengio and Russell), and Blake thinking is close to Yann's, given they are part of a similar philosophical bent. Why you Might Want to Talk to Skeptics Another exercise I found insightful was (mostly incorrectly) assessing people's views on AI Alignment and AI timelines, which made me understand better (thanks Cunningham's law!) the views of optimists (they turned out to be pretty close to Richard Ngo's reasons for optimism at 11:36 here). In any case, I recommend to people who are in touch with ML researchers or practitioners to 1) get to a level where they feel comfortable steelmanning them 2) do a write-up of their positions on LW/EAF. That would help nail down the community's understanding of what arguments are convincing or not, and what would make them change their mind. To that end, here are what Blake has to say about his position on AGI and what could make his change his mind about existential risk. Generalizing to "All Sort of Tasks We Might Want It To do" "We know from the no free lunch theorem that you cannot have a learning algorithm that outperforms all other learning algorithms across all tasks. [...] Because the set of all possible tasks will include some really bizarre stuff that we certainly don't need our AI systems to do. And in that case, we can ask, “Well, might there be a system that is good at all the sorts of tasks that we might want it to do?” Here, we don't have a mathematical proof, but again, I suspect Yann's intuition is similar to mine, which is that you could have systems that are good at a remarkably wide range of things, but it's not going to cover everything you could possibly hope to do with AI or want to do with AI." Contra Transfer Learning from Scaling "What's happened with scaling laws is that we've seen really impressive ability to transfer to related tasks. So if you train a large language model, it can transfer to a whole bunch of language-related stuff, very impressively. And there's been some funny work that shows that it can even transfer to some out-of-domain stuff a bit, but there hasn't been any convincing demonstration that it transfers to anything you want. And in fact, I think that the recent paper. The Gato paper from DeepMind actually shows, if you look at their data, that they're still getting better transfer effects if you train in domain than if you train across all possible tasks." On Recursive Self-Improvement "Per this specificity argument, my intuition is that an AI that is good at writing AI code might not have other types of intelligence. And so this is where I'm less concerned about the singularity because if I have an AI system that's really good at coding, I'm not convinced that it's going to be good at other...

Blake Richards is an Assistant Professor in the Montreal Neurological Institute and the School of Computer Science at McGill University and a Core Faculty Member at MiLA. He thinks that AGI is not a coherent concept, which is why he ended up on a recent AGI political compass meme. When people asked on Twitter who was the edgiest people at MiLA, his name got actually more likes than Ethan, so hopefully, this podcast will help re-establish the truth. Transcript: https://theinsideview.ai/blake Video: https://youtu.be/kWsHS7tXjSU Outline: (01:03) Highlights (01:03) AGI good / AGI not now compass (02:25) AGI is not a coherent concept (05:30) you cannot build truly general AI (14:30) no "intelligence" threshold for AI (25:24) benchmarking intelligence (28:34) recursive self-improvement (34:47) scale is something you need (37:20) the bitter lesson is only half-true (41:32) human-like sensors for general agents (44:06) the credit assignment problem (49:50) testing for backpropagation in the brain (54:42) burstprop (bursts of action potentials), reward prediction errors (01:01:35) long-term credit-assignment in reinforcement learning (01:10:48) what would change his mind on scaling and existential risk

Join Aalia and Marion Van Horn, Ph.D. as they discuss the concept of neuroplasticity and the impact of our early life experiences on brain development. Marion obtained her Ph.D. in Neurophysiology from McGill University and is currently a postdoc researcher at the Montreal Neurological Institute, where she studies mechanisms underlying developmental neuroplasticity. She studies how external factors, like experiences and environment, can influence how neurons explore and is trying to better understand the nitty gritty signaling pathways underlying how neurons make strong synaptic connections with other neurons to make functional neural circuits in the brain. In addition to her research, Marion is actively involved in science communication and knowledge translation. Marion leans on the research that tells us that early life experiences are important for shaping the brain and uses this as an excuse to slow down and appreciate the time she has with her children. And while parenting is not easy, she reminds us that the books we read our children, the conversations we have and the banana bread we make are all experiences that will help build a better brain in the long run. She is the producer and co-host of the Curious Neuron Podcast, which provides zero-cost, evidence-backed information for parents and caregivers. 

In this episode we speak to Dr. Robert Zatorre. Dr. Zatorre is a cognitive neuroscientist at the Montreal Neurological Institute of McGill University. He helped to pioneer a new field of study that focuses on the intersection of music and the brain and is a founder and the co-director of an international laboratory for Brain, Music, and Sound research. We all know that music gives us pleasure but you'll be fascinated to find out exactly why. What is happening inside our heads when we listen to music? Why do some people like music more than others? Why do some songs become earworms and get stuck in our head? In this episode we sit down with a world renowned expert to answer these and many other fascinating questions. Visit Dr. Zatorre's Auditory Cognitive Neuroscience Laboratory at: zlab.mcgill.ca/ to learn more and access the lab's original research publications. ... Beatseeker has been selected by Feedspot as one of the Top Music Technology Podcasts on the web: https://blog.feedspot.com/music_technology_podcasts/ Learn more: beatseeker.fm Insta: @beatseekerpod Twitter: @beatseekerpod Facebook: facebook.com/beatseekerpod Patreon: https://www.patreon.com/beatseeker Beatseeker is sponsored by the Boombox Music League: boomboxsoftware.com

In the first episode of our fifth season, our host Peter Brenders talks with Dr. Angela Genge, Executive Director of the Clinical Research Unit at the Montreal Neurological Institute, about CNS research, recruiting patients for rare disease trials and the effect of Covid-19 on clinical trials. Get on the email list at healthbiz.substack.com

The hashtag #HydrationChallenge has made its rounds all-around social media trending pages recently. While it sounds good on the surface, keep yourself hydrated consistently and constantly, the science behind it is less than assuring. GUEST: Dr. Tim Caulfield, Canada Research Chair in Health Law and Policy, and a Professor with the Faculty of Law and School of Public Health at the University of Alberta Elon Musk and his Neuralink Corporation are developing a brain implant chip that can augment your mental functions with AI. What could this look like in 10 years? What are the limits of this? GUEST: Blake Richards, Assistant Professor in the Montreal Neurological Institute and the School of Computer Science at McGill University and a Canada A.I. Chair at the Quebec Artificial Intelligence Institute The remaining members of Queen rake in a truly outstanding amount of royalties from the Freddie Mercury written hit Bohemian Rhapsody alone. How much? Scott and his guest will tell you. As well the band has rereleased a classic album on a vintage format... but it's not vinyl, nor is it CD. GUEST:: Lou Molinaro, Member of The Hamilton Music Advisory Team and Instructor at the Harris Institute for Music See omnystudio.com/listener for privacy information.

In this episode, Marion shares what it's like to be a neuroscientist studying developmental neuroplasticity. She obtained her Ph.D. in Neurophysiology from McGill University and is currently a postdoc researcher at the Montreal Neurological Institute, where she studies the molecular and cellular mechanisms underlying developmental neuroplasticity. She studies how external factors can influence how neurons explore and is trying to better understand the nitty-gritty signaling pathways underlying how neurons make synaptic connections with other neurons to make functional neural circuits. Marion is also a mom of three and is fascinated about how early life experiences can influence the development of her kids! Marion tells us about her research in the lab studying neuroplasticity in tadpoles and tells about how she applies what she has learned in her research to her own children's development – including why she prioritizes getting her kids 1-3 hours outside every day! Want the links to the scientific articles we mentioned? Click the link!https://www.curiousneuron.com/podcast/2021/5/13/ep-26-how-to-support-your-childs-brain-developmentJoin us on Instagram:@curiousneuronpodcast@curious_neuronPlease rate this podcast and leave us a review to help support us!

Dr. Angela Genge is Director of the Clinical Research Unit at the Montreal Neurological Institute. She is a neuromuscular neurologist and leads the Amyotrophic lateral sclerosis (ALS) clinical program and multidisciplinary clinic. Dr. Genge has received numerous awards, most recently the 2018 Forbes Norris Award, the DIVA of Distinction Award, and the Governor General Diamond Jubilee Award. Ms. Leigh Stephens is a social worker and a psychosocial counsellor at the ALS Society of Quebec. She supports people living with ALS and their caregivers at every stage of the disease, from diagnosis through end of life and bereavement. Her work developing programs and services for caregivers led to her involvement in the consultation process for the development of the National Policy for Caregivers in Quebec. Dr. Genge will speak about ALS, how it progresses and what treatments are available. Ms. Stephens will provide an understanding of the types of programs and services that exist for persons living with ALS and their caregivers. We would like to thank the Lindsay Memorial Foundation for sponsoring this episode of McGill Cares. Original Air Date: December 16, 2020 McGill Cares is a weekly webcast series designed to support informal caregivers. During candid, 30-minute interviews with leading experts, Claire Webster, Alzheimer Care Consultant and Founder of the McGill Dementia Education Program, explores topics related to caring for a loved one with dementia. For more information about the McGill Dementia Education Program or to make a donation, please visit www.mcgill.ca/dementia. If you have specific topics or questions that you would like us to address during our weekly webcasts, please email us at dementia@mcgill.ca.

"Imaging Focal Hyperexcitability in the Epileptic Brain" The Anne Klibanski Visiting Lecture Series was created to support and advance the careers of women. These lectures bring together faculty from institutions that have hosted Anne Klibanski Scholars with MGH scholars, on topics that overlap both research areas. This lecture was be given by Alice Lam, MD, PhD, Assistant Professor of Neurology, MGH/HMS and Eliane Kobayashi, MD, PhD, Assistant Professor of Neurology, Montreal Neurological Institute, McGill University. Webinar available at https://youtu.be/S45LKp903tY

Stefania tells the story of Dr. WILDER PENFIELD, founder of the Montreal Neurological Institute, and one of Canada's first Neurosurgeons whose work on mapping the human brain led to new methods and techniques in brain surgery, and further developed the surgical treatment of Epilepsy. Born: January 26, 1891, Spokane, Washington; Died: April 5, 1976, Montreal, QC.   Episode Sources: 1. Wikipedia: en.wikipedia.org/wiki/Wilder_Penfield 2. From the Mcgill - Neuro Page on Wilder Graves Penfield. https://www.mcgill.ca/neuro/about/history/notable-figures/wilder-graves-penfield 3. New York Times: "W.G. Penfield, Neurologist, Dies". April 6, 1976. https://www.nytimes.com/1976/04/06/archives/wg-penfield-neurologistdies-refined-techniques-to-treat-epilepsy.html 4. The Legacy of Patient H.M. for Neuroscience. Larry R. Squire. NCBI. PMC. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649674/ 5. Why Wilder Penfield is the Greatest McGillian, by Brenda Milner . June 18, 2011. https://www.youtube.com/watch?v=zkgzokHDD2k 6. Heritage Minutes: Wilder Penfield. https://en.wikipedia.org/wiki/Wilder_Penfield 7. Penfield, Epilepsy and the Functional Brain https://www.youtube.com/watch?v=4EDPLccSoO8 8. Neurosurgery, Groundhog day, and Dr Penfield. https://www.youtube.com/watch?v=iePt8ZioO6c&feature=emb_title 9. Maclean's Magazine. "Interview with Dr. Wilder Penfield". April 19, 1976. https://archive.macleans.ca/article/1976/4/19/interview 10. Geni. www.geni.com. Wilder Graves Penfield, OM, CC, CMG, FRS. https://www.geni.com/people/Wilder-Graves-Penfield-OM-CC-CMG-FRS/6000000024062642437  

Gary Null Show Notes 02/08/21 CDC: Over 500 Deaths Now Following mRNA Experimental Injections – “Vaccine Hesitancy” Increasing Invasive Insects and Diseases Are Killing Our Forests How ExxonMobil Uses Divide and Rule to Get Its Way in South America How the Pandemic Left the $25 Billion Hudson Yards Eerily Deserted Bayer makes new $2 billion plan to head off future Roundup cancer claims Billionaire capitalists are designing humanity’s future. Don’t let them Citizen scientists are filling research gaps created by the pandemic After COVID, Davos Moves to The “Great Reset” COVID-19: Here’s why global travel is unlikely to resume ‘till 2024     The Acute and Chronic Cognitive Effects of a Sage Extract: A Randomized, Placebo Controlled Study in Healthy Humans Northumbria University (UK), January 31, 2021 The sage (Salvia) plant contains a host of terpenes and phenolics which interact with mechanisms pertinent to brain function and improve aspects of cognitive performance. However, previous studies in humans have looked at these phytochemicals in isolation and following acute consumption only. A preclinical in vivo study in rodents, however, has demonstrated improved cognitive outcomes following 2-week consumption of CogniviaTM, a proprietary extract of both Salvia officinalis polyphenols and Salvia lavandulaefolia terpenoids, suggesting that a combination of phytochemicals from sage might be more efficacious over a longer period of time. The current study investigated the impact of this sage combination on cognitive functions in humans with acute and chronic outcomes. Participants (n = 94, 25 M, 69 F, 30–60 years old) took part in this randomised, double-blind, placebo-controlled, parallel groups design where a comprehensive array of cognitions were assessed 120- and 240-min post-dose acutely and following 29-day supplementation with either 600 mg of the sage combination or placebo. A consistent, significant benefit of the sage combination was observed throughout working memory and accuracy task outcome measures (specifically on the Corsi Blocks, Numeric Working Memory, and Name to Face Recall tasks) both acutely (i.e., changes within day 1 and day 29) and chronically (i.e., changes between day 1 to day 29). These results fall slightly outside of those reported previously with single Salvia administration, and therefore, a follow-up study with the single and combined extracts is required to confirm how these effects differ within the same cohort. In conclusion, we have observed a consistent significant benefit of a sage combination intervention  in healthy adult humans on working memory and accuracy of performance cognitive domains. This significant activity was observed both acutely (after just 2 h following consumption) and chronically (after 29 days of administration). The pattern and magnitude of significance points towards an increase in product efficacy over the administration period and, taken together, suggests that future trials should focus on disentangling the working and spatial memory effects of this intervention in humans with an extended timeframe of perhaps several months. Validating the CaMKII mechanism in humans would also be advantageous. Blink! The link between aerobic fitness and cognition University of Tsukuba (Japan), February 3, 2021 Although exercise is known to enhance cognitive function and improve mental health, the neurological mechanisms of this link are unknown. Now, researchers from Japan have found evidence of the missing link between aerobic fitness and cognitive function. In a study published in Medicine & Science in Sports & Exercise, researchers from the University of Tsukuba revealed that spontaneous eye blink rate (sEBR), which reflects activity of the dopamine system, could be used to understand the connection between cognitive function and aerobic fitness. The dopaminergic system is known to be involved in physical activity and exercise, and previous researchers have proposed that exercise-induced changes in cognitive function might be mediated by activity in the dopaminergic system. However, a marker of activity in this system was needed to test this hypothesis, something the researchers at the University of Tsukuba aimed to address. “The dopaminergic system is associated with both executive function and motivated behavior, including physical activity,” says first author of the study Ryuta Kuwamizu. “We used sEBR as a non-invasive measure of dopaminergic system function to test whether it could be the missing link between aerobic fitness and cognitive function.” To do this, the researchers asked healthy participants to undergo a measure of sEBR, a test of cognitive function, and an aerobic fitness test. They also measured brain activity during the cognitive task using functional near-infrared spectroscopy. “As expected, we found significant correlations between aerobic fitness, cognitive function, and sEBR,” explains Professor Hideaki Soya, senior author. “When we examined these relationships further, we found that the connection between higher aerobic fitness and enhanced cognitive function was mediated in part by dopaminergic regulation.” Furthermore, activity in the left dorsolateral prefrontal cortex (l-DLPFC) during the cognitive task was the same or lower in participants with higher sEBR compared with lower sEBR, even though those with higher sEBR appeared to have greater executive function, and thus higher neural efficiency. “Although previous studies have indicated that aerobic fitness and cognitive function are correlated, this is the first to provide a neuromodulatory basis for this connection in humans. Our data indicate that dopamine has an essential role in linking aerobic fitness and cognition,” says first author Kuwamizu. Given that neural efficiency in the l-DLPFC is a known characteristic of the dopaminergic system that has been observed in individuals with higher fitness and executive function, it is possible that neural efficiency in this region partially mediates the association between aerobic fitness and executive function. Furthermore, physical inactivity may be related to dopaminergic dysfunction. This information provides new directions for research regarding how fitness affects the brain, which may lead to improved exercise regimens. For instance, exercise that specifically focuses on improving dopaminergic function may particularly boost motivation, mood, and mental function. Vegan diet better for weight loss and cholesterol control than Mediterranean diet Physicians Committee for Responsible Medicine, February 5, 2021 A vegan diet is more effective for weight loss than a Mediterranean diet, according to a groundbreaking new study that compared the diets head to head. The randomized crossover trial, which was published in the Journal of the American College of Nutrition, found that a low-fat vegan diet has better outcomes for weight, body composition, insulin sensitivity, and cholesterol levels, compared with a Mediterranean diet. The study randomly assigned participants–who were overweight and had no history of diabetes–to a vegan diet or a Mediterranean diet in a 1:1 ratio. For 16 weeks, half of the participants started with a low-fat vegan diet that eliminated animal products and focused on fruits, vegetables, whole grains, and legumes. The other half started with the Mediterranean diet, which followed the PREDIMED protocol, which focuses on fruits, vegetables, legumes, fish, low-fat dairy, and extra virgin olive oil, while limiting or avoiding red meat and saturated fats. Neither group had a calorie limit, and participants did not change exercise or medication routines, unless directed by their personal doctors. As part of the crossover design, participants then went back to their baseline diets for a four-week washout period before switching to the opposite group for an additional 16 weeks. The study found that within 16 weeks on each diet: Participants lost an average of 6 kilograms (or about 13 pounds) on the vegan diet, compared with no mean change on the Mediterranean diet. Participants lost 3.4 kg (about 7.5 pounds) more fat mass on the vegan diet. Participants saw a greater reduction in visceral fat by 315 cm3 on the vegan diet. The vegan diet decreased total and LDL cholesterol levels by 18.7 mg/dL and 15.3 mg/dL, respectively, while there were no significant cholesterol changes on the Mediterranean diet. Blood pressure decreased on both diets, but more on the Mediterranean diet (6.0 mm Hg, compared to 3.2 mmHg on the vegan diet). “Previous studies have suggested that both Mediterranean and vegan diets improve body weight and cardiometabolic risk factors, but until now, their relative efficacy had not been compared in a randomized trial,” says study author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee. “We decided to test the diets head to head and found that a vegan diet is more effective for both improving health markers and boosting weight loss.” The authors note that the vegan diet likely led to weight loss, because it was associated with a reduction in calorie intake, increase in fiber intake, decrease in fat consumption, and decrease in saturated fat consumption. “While many people think of the Mediterranean diet as one of the best ways to lose weight, the diet actually crashed and burned when we put it to the test,” says study author Neal Barnard, MD, president of the Physicians Committee. “In a randomized, controlled trial, the Mediterranean diet caused no weight loss at all. The problem seems to be the inclusion of fatty fish, dairy products, and oils. In contrast, a low-fat vegan diet caused significant and consistent weight loss.” “If your goal is to lose weight or get healthy in 2021, choosing a plant-based diet is a great way to achieve your resolution,” adds Dr. Kahleova. Study finds childhood diet has lifelong impact University of California at Riverside, February 3, 2021 Eating too much fat and sugar as a child can alter your microbiome for life, even if you later learn to eat healthier, a new study in mice suggests. The study by UC Riverside researchers is one of the first to show a significant decrease in the total number and diversity of gut bacteria in mature mice fed an unhealthy diet as juveniles. “We studied mice, but the effect we observed is equivalent to kids having a Western diet, high in fat and sugar and their gut microbiome still being affected up to six years after puberty,” explained UCR evolutionary physiologist Theodore Garland. A paper describing the study has recently been published in the Journal of Experimental Biology. The microbiome refers to all the bacteria as well as fungi, parasites, and viruses that live on and inside a human or animal. Most of these microorganisms are found in the intestines, and most of them are helpful, stimulating the immune system, breaking down food and helping synthesize key vitamins. In a healthy body, there is a balance of pathogenic and beneficial organisms. However, if the balance is disturbed, either through the use of antibiotics, illness, or unhealthy diet, the body could become susceptible to disease. In this study, Garland’s team looked for impacts on the microbiome after dividing their mice into four groups: half fed the standard, ‘healthy’ diet, half fed the less healthy ‘Western’ diet, half with access to a running wheel for exercise, and half without. After three weeks spent on these diets, all mice were returned to a standard diet and no exercise, which is normally how mice are kept in a laboratory. At the 14-week mark, the team examined the diversity and abundance of bacteria in the animals. They found that the quantity of bacteria such as Muribaculum intestinale was significantly reduced in the Western diet group. This type of bacteria is involved in carbohydrate metabolism. Analysis also showed that the gut bacteria are sensitive to the amount of exercise the mice got. Muribaculum bacteria increased in mice fed a standard diet who had access to a running wheel and decreased in mice on a high-fat diet whether they had exercise or not. Researchers believe this species of bacteria, and the family of bacteria that it belongs to, might influence the amount of energy available to its host. Research continues into other functions that this type of bacteria may have. One other effect of note was the increase in a highly similar bacteria species that were enriched after five weeks of treadmill training in a study by other researchers, suggesting that exercise alone may increase its presence. Overall, the UCR researchers found that early-life Western diet had more long-lasting effects on the microbiome than did early-life exercise. Garland’s team would like to repeat this experiment and take samples at additional points in time, to better understand when the changes in mouse microbiomes first appear, and whether they extend into even later phases of life. Regardless of when the effects first appear, however, the researchers say it’s significant that they were observed so long after changing the diet, and then changing it back. The takeaway, Garland said, is essentially, “You are not only what you eat, but what you ate as a child!” Turns Out Maple Syrup Is Anticarcinogenic Kindai University (Japan), February 2, 2021 Darker coloured syrup is suggested as healthier than lightly coloured syrup. Maple syrup is a classic natural sweetener that has been making a comeback recently as an alternative to refined sugar. The syrup is tapped from different species of maple trees, with the Canadian province of Quebec being a top producer. Along with a rich and complex flavor, maple syrup offers an abundance of amino acids, manganese and zinc, as well as phenolic compounds, including lignans and coumarin. A new study called “Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells” was guided by Dr. Tetsushi Yamamoto, a molecular and cell biologist from the Faculty of Pharmacy at Kindai University in Osaka, Japan. The research evaluated the effect of three different types of maple syrup. The main objective was to identify if maple syrup could be used as a phytomedicine within cancer treatment. Dr. Yamamoto and his research team classified the different types of maple syrup according to colour, as well as cell proliferation, and migration and invasion capability for colorectal cell cancer (CRC). Results showed that CRC cells administered maple syrup showed lower rates of carcinogenic cells when compared with cells administered only sucrose. Additionally, the study suggests that maple syrup should not only be classified by its sugar content, but also according to its nutritional and physiochemical components. This study showed that maple syrup, particularly when coloured darker, might be suitable as a phytomedicine, which may offer a more gentle alternative to traditional chemotherapy. This outstanding revelation is in contrast to other studies, which support the idea that sugar perpetuates cancer and other chronic diseases. However, this disparity might concern diverse types of sugar, including sucrose, fructose and glucose. Also, sugar behaves differently when consumed in diverse nutritional contexts. In this context, researchers experimented with different sucrose concentrations, ranging from 0.1% to 10%. Results showed that only maple syrup with a 10% concentration of sucrose inhibited colorectal cancer cell growth. The study explained that this is because higher concentrations might have cytotoxic effects due to high osmotic pressure. Brains are more plastic than we thought McGill University, January 31, 2021 Practice might not always make perfect, but it’s essential for learning a sport or a musical instrument. It’s also the basis of brain training, an approach that holds potential as a non-invasive therapy to overcome disabilities caused by neurological disease or trauma. Research at the Montreal Neurological Institute and Hospital of McGill University (The Neuro) has shown just how adaptive the brain can be, knowledge that could one day be applied to recovery from conditions such as stroke. Researchers Dave Liu and Christopher Pack have demonstrated that practice can change the way that the brain uses sensory information. In particular, they showed that, depending on the type of training done beforehand, a part of the brain called the area middle temporal (MT) can be either critical for visual perception, or not important at all. Previous research has shown the area MT is involved in visual motion perception. Damage to area MT causes “motion blindness”, in which patients have clear vision for stationary objects but are unable to see motion. Such deficits are somewhat mysterious, because it is well known that area MT is just one of many brain regions involved in visual motion perception. This suggests that other pathways might be able to compensate in the absence of area MT. Most studies have examined the function of area MT using a task in which subjects view small dots moving across a screen and indicate how they see the dots moving, because this has been proven to activate area MT. To determine how crucial MT really was for this task, Liu and Pack used a simple trick: They replaced the moving dots with moving lines, which are known to stimulate areas outside area MT more effectively. Surprisingly, subjects who practiced this task were able to perceive visual motion perfectly even when area MT was temporarily inactivated. On the other hand, subjects who practiced with moving dots exhibited motion blindness when MT was temporarily deactivated. The motion blindness persisted even when the stimulus was switched back to the moving lines, indicating that the effects of practice were very difficult to undo. Indeed, the effects of practice with the moving dot stimuli were detectable for weeks afterwards. The key lesson for brain training is that small differences in the training regimen can lead to profoundly different changes in the brain. This has potential for future clinical use. Stroke patients, for example, often lose their vision as a result of brain damage caused by lack of blood flow to brain cells. With the correct training stimulus, one day these patients could retrain their brains to use different regions for vision that were not damaged by the stroke. “Years of basic research have given us a fairly detailed picture of the parts of the brain responsible for vision,” says Christopher Pack, the paper’s senior author. “Individual parts of the cortex are exquisitely sensitive to specific visual features – colors, lines, shapes, motion – so it’s exciting that we might be able to build this knowledge into protocols that aim to increase or decrease the involvement of different brain regions in conscious visual perception, according to the needs of the subject. This is something we’re starting to work on now.” Higher Fiber Intake May Improve Lung Function   University of Nebraska, January 28, 2021 Eating a fiber-rich diet may help protect you against lung disease, a new study suggests. “Lung disease is an important public health problem, so it’s important to identify modifiable risk factors for prevention,” study author Corrine Hanson, an associate professor of medical nutrition at the University of Nebraska Medical Center, said in a journal news release. “However, beyond smoking very few preventative strategies have been identified. Increasing fiber intake may be a practical and effective way for people to have an impact on their risk of lung disease,” she added. The findings were published recently in the Annals of the American Thoracic Society. Researchers looked at federal government data from almost 2,000 American adults. They were between 40 and 79 years old. The researchers found that 68 percent of those who had the highest fiber consumption (about 18 grams or more daily) had normal lung function compared to 50 percent for those with the lowest fiber intake. And, only 15 percent of those who ate a lot of fiber had airway restriction, but 30 percent of those with the lowest fiber intake did, the study showed. People with the highest fiber consumption also did better on two important breathing tests. They had larger lung capacity and could exhale more air in one second, the study said. Although the study found a link between fiber consumption and better lung health, it wasn’t designed to prove a cause-and-effect relationship. But, if the findings are confirmed in future studies, public health campaigns may one day “target diet and fiber as safe and inexpensive ways of preventing lung disease,” Hanson said. Previous research has suggested a diet high in fiber protects against heart disease and diabetes, and that fiber reduces inflammation in the body, the researchers said.

Dr. Marion Van Horn is a Research Associate at the Montreal Neurological Institute whose work focuses on brain development, developmental plasticity, and synaptic pruning. She is also a mom of three, and as a mom, she has some amazing techniques for supporting your kids’ brain development. We also dive into how we can protect ourselves and our families from COVID-19. You will learn about... What Dr. Marion researches in her lab What neuroplasticity is and how to support it within children The importance of play for kids The benefits of lowering expectations How much time we need to spend outside Getting enough sleep and sticking to a routine Improving synaptic pruning The role of nutrition in cognitive development How we can support ourselves against COVID-19 during pregnancy Resources: LinkedIn: https://www.linkedin.com/in/marion-van-horn-phd-b937b35/ (linkedin.com/in/marion-van-horn-phd-b937b35) Twitter: https://twitter.com/marionvanhorn (@marionvanhorn) Read: https://www.goodreads.com/book/show/34466963-why-we-sleep ("Why We Sleep") Connect with Kelly: https://kellyleveque.com/ (kellyleveque.com) Instagram: https://www.instagram.com/bewellbykelly/ (@bewellbykelly) Facebook: https://www.facebook.com/bewellbykelly/ (www.facebook.com/bewellbykelly) Be Well By Kelly is a production of http://crate.media (Crate Media)

The book Fundamentals of Human Neuropsychology was born of a need that Dr. Bryan Kolb recognized while completing his postdoctoral fellowship at the Montreal Neurological Institute with Dr. Brenda Milner.  Dr. Kolb had asked his colleagues for a textbook on the human brain and, finding none, decided to create a course about “neuropsychology.”  Now, Drs. Kolb and Whishaw’s textbook is about to be released in its 8th edition.  John and Ryan talk with Dr. Kolb about his book, the contribution of animal research to human neuropsychology, the importance of the history of our field, advice on working with a co-author, and much more. Show notes are available at www.NavNeuro.com/60 _________________ If you’d like to support the show, here are a few easy ways: 1) Get APA-approved CE credit for listening to episodes: www.NavNeuro.com/INS  2) Tell your friends and colleagues about it 3) Subscribe (free) and leave an Apple Podcasts rating/review: www.NavNeuro.com/itunes 4) Contribute to the discussion in the comments section of the website (click the episode link listed above) or on Twitter (@NavNeuro)   Thanks for listening, and join us next time as we continue to navigate the brain and behavior! [Note: This podcast and all linked content is intended for general educational purposes only and does not constitute the practice of psychology or any other professional healthcare advice and services. No professional relationship is formed between hosts and listeners. All content is to be used at listeners’ own risk. Users should always seek appropriate medical and psychological care from their licensed healthcare provider.]

Our guest this week is Lani Cupo, a multifaceted and tempestuous PhD student in Neuroscience. In this episode we discuss the seduction of the cognitive sciences, the integrated program in neuroscience offered through the Montreal Neurological Institute, the effect of perspective-taking on the perception of Native American art using priming, quantitative and qualitative analysis, the suppression of unwated thoughts, what it means to be WEIRD, biased and prejudiced; we talk animal vs. human research, taking pictures of the brain with giant magnets and other imaging techniques, the effects of maternal illness and THC (the psychoactive ingredient in marijuana, weed, pot, cannabis, etc.) exposure on disorders in offspring, how a mother's compromised immune system affects fetal development, jelly-bean mice, what we learn from a baby's first poop (!), the importance of laying the foundation of a solid work-life balance early on in your career, and finally my own question gets flipped on me! It's another jam packed episode so tune in, and as always, you can find and connect with us on Facebook, Instagram and Twitter! Your feedback is invaluable, so if you like what you heard or have an idea of how the podacast could be improved, we want to hear from you -- shoot us a message, DM, or email at abstractcast@gmail.com Thanks for listening! --- Send in a voice message: https://anchor.fm/abstractcast/message

How does the brain change itself, and can those changes be passed on to the next generation? ‘Yes’ and ‘yes’ according to Dr. Bryan Kolb, a neuroscientist at the University of Lethbridge, author of a classic neuropsychology textbook and a recipient of Canada’s highest civilian honor. Listen in to learn about brain plasticity as well as epigenetics, the science of how genes flip on and off and can be inherited in their new state. TRANSCRIPT: Intro: 0:01 Inventors and their inventions. Welcome to Radio Cade the podcast from the Cade Museum for Creativity and Invention in Gainesville, Florida. The museum is named after James Robert Cade, who invented Gatorade in 1965. My name is Richard Miles. We’ll introduce you to inventors and the things that motivate them, we’ll learn about their personal stories, how their inventions work and how their ideas get from the laboratory to the marketplace. Richard Miles: 0:38 Brain plasticity, and epigenetics. What do those terms mean? And why do they matter? I’m your host Richard Miles, and I’m very pleased to welcome a very distinguished guest, Dr. Bryan Kolb neuroscientist at the University of Lethbridge in Canada, the author of numerous books and articles on neuropsychology and the recipient of the order of Canada, Canada’s highest, Civilian honor. Welcome to Radio Cade Bryan. Bryan Kolb: 0:59 Thank you. Richard Miles: 1:01 Bryan. I read somewhere that your groundbreaking textbook Fundamentals of Neuropsychology, is the most stolen book in England. What is up with that? Bryan Kolb: 1:08 Well, apparently it’s true. It’s stolen form libraries that obviously doesn’t happen in Canada or the U.S. People buy the book. We had a heck of a time getting it published in the late 1970s, because nobody believed there was such a field and it turns out there is and the book did very well. Richard Miles: 1:24 For an author obviously an author would like to get paid on the sales, but to have your book stolen probably better than your book being dropped off at used bookstores. But let’s talk about that. The book itself was very important because it was pathbreaking breaking . It’s published in , I think in 1980. And you talked about brain plasticity, not just that, but that was one of the fundamental things. And basically your definition, I believe is the ability of the brain to reorganize its structure, function and connections in response to experiences. So why don’t you sort of walk our listeners through, what does that mean? How can we think about brain plasticity in a useful way? Bryan Kolb: 2:01 If you imagine being born into the world, the brain has no idea what world its going to be, could be in Alaska? It could be at the equator. You could be in Africa. And so the brain biologically needs to be able to change itself, to adapt to the environment that it’s in. That’s sort of the background as to why evolution would have done this. It’s not just true of us. It’s true in worms. So all animals have this capacity to change their brain response to the environment that they find themselves in. And of course, if your listeners would learn anything from this discussion today, we have to change their brains. Somehow distorted material, the brain has to change. It’s just not magic. Richard Miles: 2:39 So If I understand this correctly and we’re not stuck with the brain were born with right? Basically from the minute we’re born, the brain is constantly reshaping itself. Give me a magnitude of the degree to what we’re talking about. Is it just a little bit that the brain sort of prunes a few neurons here and there and adds , or how dramatic is it? Say we take a , a new born and we look at them when they’re one year old or five years old or 12 years old, what kind of changes have occurred in the interim in terms of the brain changing itself? Bryan Kolb: 3:11 So they, the changes are not small there quite dramatic. So when we’re born, we have twice as many neurons as we’re going to need. Twice as many as we have now, which seems a little odd. And then over the next couple of years, we make connections at an enormous rate. And we ended up with far more connections than we need. And so around age two, we start getting rid of them. And depending on which part of the brain we’re looking at, it’s going to begin around to other regions. The higher levels of cognition is later. Let’s say, we’re starting to lose the frontal connections and neurons around age five. We will lose half of them and at the beginning of adolescents or puberty the rate we lose them at is remarkable. It’s about a hundred thousand connections per second. It’s a hundred thousand, a hundred thousand, a hundred thousand, a hundred thousand. So if you think about 13 year old girls, they are not the easiest group to deal with because their brain is changing so fast. The kids of course are inventing themselves at that age. They’re becoming who they’re going to be. And what that means is they’re creating the brain of the environment that they’re headed into. So if you look at a one year old, the one year old still doesn’t really know what the environment’s going to be certainly is growing connections. The neurons aren’t being born or not many, any longer. And then as the child begins to adapt to the environment that it’s in, whatever that happens to be, then it starts to change. So if you think about language, if you imagine a child who’s born in a house, or a home that speaks Japanese or Korean, they’re not going to hear the sounds L or R. But they can discriminate those sounds when they’re six months old, but as time goes on, they start losing the ability to make those sound discriminations . And so as an adult, they have this difficulty discriminating, L and R. Similarly, if we’re born in a house that speaks English, there are sounds that other languages that we simply cannot discriminate once we’re adults, because we lose that ability. So the brain is getting rid of things it’s not going to use, getting rid of connections that are not necessary. Now, one question you could ask is what happens if you don’t get rid of these connections? What happens if you keep them all? And the answer is cognitive disabilities. So children who do not lose a lot of these connections, cognitively are impaired. So we historically would have called them retarded. We don’t any longer, but that’s basically what it is. Richard Miles: 5:34 I remember watching one of your talks. And you talked about language and it was somewhat similar to when you buy like a new Apple product that’s sold all over the world and you see it installing the files. It installs with all sorts of Russian and Japanese and Portuguese, I guess, to make your keyboard compatible or something like that. Is that sort of what we’re talking about, that a newborn has basically all of this software loaded to do lots of different things, but based on the environment, they’re not going to need all that. And what I found was fascinating is that it’s counterintuitive that that loaded up brain, I guess, is somewhat of a disadvantage and that you want to sort of prune or make it more efficient. Is that more or less accurate? Bryan Kolb: 6:14 That’s a wonderful analogy. Yeah, that’s exactly right. I’m going to use that in the future. Yeah. That’s, it’s fully loaded, ready to go, but it’s not efficient. And so if we can make things more efficient, then we’re going to have a greater cognitive capacity. Richard Miles: 6:29 Well, good. I’m glad I got the analogy, right . I’ve had guests where I rolled out an analogy and they, and they said , no, that’s completely wrong. Okay. Well, I clearly didn’t understand the concept. So we’ve described plasticity the ability of the brain to change itself. And you’ve also done a lot on something called epigenetics. So before we go into the implications, all this, certainly from an educational perspective, why don’t you also define what epigenetics is? So that way we can talk it both in the same conversation. Bryan Kolb: 6:57 Sure. So if you look at any cell in the body, it has the same DNA. So cells that make your skin and your bones, your eyes, your brain all have the same DNA, yet the cells are different. And so the question is, why are they different? Well, they’re different because different genes are turned on and different genes are turned off. So the idea of epigenetics is that gene expression, the turning on or turning off of genes is regulated by experience, by things that are going on around us. And those things could be inside us or those things could be outside of us. So the idea is that if you’re going to change the brain, if you’re going to have plastic changes, the changes are going to result from changes in the activity of genes. This activity of genes is affected by experience. And so the idea of epigenetics is that we have a certain experience that might be a stressful event. It might be a wonderful event, might be a drug who knows what it is, but those things will change the expression of genes, which changes creation of proteins, manufacturer proteins and so on in the body or in grand (inaudible). Richard Miles: 7:59 So this is really a revolutionary insight because I think prior to this, you’ve had this debate for centuries about nature versus nurture, right? What you’re born with, what you inherit as part of your genes and then your environment and all of your experiences, whether that’s the way you were raised or the way you’re educated or whatever happens to you that shapes you. But this seems to imply that it’s not just a mix of those two, they’re actually together in the form that your experiences can make you well, why don’t you explain it particularly with the role of the father, which that’s really, really fascinating that these changes occur even before somebody essentially is conceived. Bryan Kolb: 8:38 That’s right in fact, it’s paradoxical. It seems at first that the father could have a bigger influence on the gene expression of the offspring than the mom. But it’s related to the fact that the changes in gene expression can be transmitted by the sperm. So the idea here is that if you take the father, who’s had some sort of stressful event, maybe was a soldier in Iraq or something, just a horrible experience. That’s going to change the gene expression in the sperm of the dad, which as a result is going to change the way in which the developing brain or his offspring is going to progress. It’s true that the mom has also evolved but her eggs don’t change. So the eggs that she is born with that will eventually be used to create babies. They don’t change. They’re not changed by experiences, but the sperm is, cause the sperm dies every 40 days or so when you create new sperm. And so that new sperm is being affected by the experiences that the dad has had. That means that the same dad could have a different kind of gene expression transmitted to different children, depending on the experiences that they’ve had in the previous two or three months or maybe longer. So that’s the idea there, and these changes can cross generations or can be shown in the grandchildren. Maybe the great grandchildren who knows defect gets much smaller over time. So if you have your daughter or your son and they have experiences too, and so it’s going to affect change expression. And so the influence of that event, that the father had pre conceptually to you, is going to start decreasing, but nonetheless, there is a footprint of it there. If you go back to this idea that epigenetics, if you remember, there was a scientist called Lamarck. Lamarck believed there was, that genes could learn essentially that learning, could it be transmitted from generation to generation. And people thought decided this was crazy. It’s not like that. Well, it turns out he was correct. He didn’t know the mechanism, but in fact it looks like that’s, what’s actually happening. So you’re right. Nature and nurture are working together, back and forth, back and forth. Richard Miles: 10:38 So just so I understand this correctly, Bryan, I can’t change my own DNA. I’m stuck with my DNA and not all genes can switch on or off. Right. You’re only talking about a certain subset of genes or do all, all genes, have the ability to essentially be turned on or turned off. Bryan Kolb: 10:55 I don’t know the answer to that, but my guess is that most of the ability to be turned on or turned off. But I imagine some can’t. Good question. Richard Miles: 11:03 You talked about the example of PTSD from someone in Iraq or war zone. I assume that also goes the other direction. For instance, if I inherited the DNA of being a very good baseball player, for instance, and then I became a great baseball player, I hit the major leagues, the likelihood, then that say my kids would inherit , that ability are now much greater, right? Because I’ve done that gene for pitching or catching or whatever I’ll ask you. Does that explain why you often see sports stars? You know, fathers and sons who are in the major leagues, whether it’s baseball or hockey or football at a rate that would be implausible, unless there’s some sort of genetic connection, right? Bryan Kolb: 11:42 Correct. We should make it clear that there’s not a gene we’re talking about multiple genes. Nothing is, it’s usually aging, the odd diseases for the most part. That’s not the case, but yeah, that would be why you get somebody like Gordie Howe and his three sons, all playing pro hockey at the same time. Richard Miles: 11:58 I always felt a little bit, sorry for maybe the one kid that didn’t get it. Right? Like there’s no Peyton Manning and Eli Manning. And I think their father was a famous quarterback as well. Right. But there’s one son that doesn’t have it. So I’ve always wondered what his Thanksgiving dinner is like at those households. Okay. So Bryan, I think I’ve got it. And I hope our listeners have got it that basically brain plasticity brain can and does change itself a lot, but there are certain windows, right? So it’s not like a continuous process that every year your brain either grows a certain number of neurons or loses them. There are windows in which that’s sort of concentrated and that your research and other people’s have found has a tremendous influence on particular education. And then everything that sort of flows from good or bad education, a lot of life outcomes are going to stem from whether you were well-educated or did well in school or , or not. So why don’t you talk a little bit about what research has shown is the correlation between those windows of brain development and future outcomes? Bryan Kolb: 13:00 Well, the earliest window obviously is the prenatal window, but the first one to three years is a window of a lot of change. Then a period it’s not quite as soon, but it’s not changing as much until the onset of puberty. And then we have this period in adolescence of huge change. Now we used to think that the brain was pretty much finished developing by about age 18, but it’s not. And so it continues on into the third decade. And so we’re looking at changes going up to say 30, 32, depending on whether you’re a man or a woman. If you ask people who are say over 40 or 50, when they became who they are, most people would say somewhere around 30, clearly there are changes that when we look back on. We can see what are going on for a long time. Then we have a reduction in plasticity, but mercifully it doesn’t stop. So that even at my age, I’m 72, I can still learn things. I don’t learn them as quickly as my grandchildren unfortunately, but I can still learn things. The brain is still plastic . However, there are disorders which the plasticity really does decline like Alzheimer’s and Parkinson’s and other demanding diseases where we now see that the brain really isn’t changing very easily. But for most people the changes can continue on into senescence, but at a very much, much slower rate, for sure. So we have these two windows one shortly after birth and the other one in early adolescence in particular. The second one’s really important because we’re worrying about kids experimenting with drugs when they’re 13, 14, when the brain is really changing. One of the things that Terry Robinson and I discovered about 20 years ago was that every psychoactive drug that you take actually produces permanent changes in the structure of neurons. And those changes that occur with kids who are experiencing with drugs have different consequences than they do with you, or me, particularly cannabis is a worry investigating the effects of cannabis at age 13, 14, 15, the effects can actually be dramatic in the twenties with respect to mental health and so on. So that’s a big worry about plasticity. There’s something that’s pathological. I just want to throw one other thing in here. That is, if you have an idea and you can remember the idea, it means that you changed your own brain, but that idea has changed the brain, which is you think about it quite remarkable, but that’s the only way you can remember it. Richard Miles: 15:20 One of the things we talk about at the Cade Museum, particularly with regards to education is the value of interactive experience that a lot of inventors, a lot of entrepreneurs often don’t do well, or haven’t done well on a classic school system. They have sort of different experiences and what I found fascinating, about one of the things that I saw you talk about was the language development skills in the first 18 months of life. And that it’s not enough to be simply exposed, to say a large vocabulary passively. You really have to get in the rhythm of being able to have a conversation in a given take away. And that has profound differences or profound outcomes on how somebody does later in life. So can you explain how exactly that works and what the research shows about those differences? Bryan Kolb: 16:08 You know , one of the metaphors we use here is serve and return. So the idea is that if you are passively listening to the language, whether it’s on TV or the radio or whatever artist in the background, you’re not actually actively engaged socially with the center of that information, but you need to be. So if I say something to you and your child, and then you respond, that’s the serve and return idea. There’s a really nice experiment, trying to teach kids. I believe it was Japanese, but it was not English, English, speaking kids. And they either saw this woman trying to teach them on TV. Or she was in the TV, the old kind of TVs , where there was a big Catholic retreat . So she’s actually there see woman , but she can actually serve and return with the kids in the one case and in the other she can’t. And I guess which kids learn Japanese, the ones who actually have the personal interaction. So the social support, the social interaction is really critical to the plastic changes in the brain. Richard Miles: 17:05 So I guess one question really is we’re recording this and then, you know, the middle of 2020 in the midst of the 19 sort of lockdown , what that means for education and schooling. Is there anything to suggest that a serve and return as you call it style online is just as effective or less effective than face to face? Because obviously there’s a whole bunch of other types of communication that go on between people face to face the visual cues and facial cues does a lot of that get lost during an online experience or the fact that you can actually talk to and be taught from somebody online. Is that good enough? Bryan Kolb: 17:41 It’s a really good question. And I’m sure there are people studying that as a professor who is going to have to be online. These students their not going to be on my screen. I won’t be able to see them. That’s impossible on Zoom to do that. And so are they going to get the same education? I doubt that, but if it’s two people as you and I are an hour on screen, I suspect that we’re going to get a lot of the serve and return affects whether children can be engaged in the same way as empirical question that I’m sure that many developmental psychologists are studying right now. It’s , it’s a really, really good question. Richard Miles: 18:15 One of the things I really want to ask you about is it seems like the most important window. If I understand your research correctly is that sort of first 18 months were certainly the absence of direct communication with an infant is really disastrous. And I think it’s from those remaining or some studies and other studies have just shown. It’s just terrible, but there are these other windows later on where you’ve got a window of learning, I guess, let me give you three scenarios and give me your reaction to these three scenarios in terms of what does the research say? If anything, about practical decisions as people trying to sort out scenario number one would be you have a 12 year old and you’re trying to decide, do I have them study music or do sports number two you’re 18 years old. And do you study chemistry or you study history and then number three late in life, you’re , let’s say 56. And should you learn French on Duolingo or just drink Bordeaux all day. Very specific nature. The third scenario it’s asking for a friend, what can you tell us about brain plasticity at those other stages, adolescence early adulthood, and then middle age ? Bryan Kolb: 19:22 Well, one of the most important things that children can do using your, I think it was age 12, piano lessons versus sports is music has a profound influence on how we age. So basically it’s like learning a foreign language. So we know that people who have musical training prior to say age 20 age, better incidence of dementia is much lower. And so on later in life music engages the entire grid. It’s a difficult decision will be, not be in sports because you need the exercise, exercise increases the blood flow into the brain. So you’d want to do both in a sense, but it’s not impossible chemistry versus history. The person in the 20th, the brain is more likely to change in positive ways. If you’re doing things that are interesting, if you’re not engaged, if I’m taking chemistry and I hate it, which was true, but let’s imagine it was, I’m not going to learn it and they’re not going to remember it. So you may be that I was fascinated with European history and I got really engaged in that. So I think it the amount of engagement that’s going to make a difference to how plastic the brain will be. In terms of the 56 year old. I’ve been playing the guitar for over 50 years. When I bought a banjo in 1988 , I never learned to play it. And so I decided this year to learn to play it. And my wife got a new piano. And so she’s taking out the piano. She took piano lessons as a child for 8 or 10 years. And then once she went to vet school and she never play it again, we’ve carted this bloody piano from place to place. So I keeps saying nobody plays it. So now she has luckily a new piano, a little baby grant . She’s taking piano lessons again, she’s close to my age. So we’re both learning to play these instruments. And now we’re playing duets together. It’s really not the Banjo, or the piano, the guitar. It’s really a lot of fun, but the brain clearly can change in the older person. I have to say, the Bordeaux helps make it fun. Richard Miles: 21:13 Well, I have another banjo story, not quite as successful. My wife gave me a banjo about 15 years ago, hoping that I would learn how to play it. I did try to learn, but it turns out we had a friend who really was quite good. And we decided just to give the banjo to him because the, some benefit for humanity would be much better fee on the banjo and not me, but he actually answered the question. I was about to ask how much research has been done, particularly on people in their later years, let’s say 50 or 60 above those who choose to do something new or resurrect something that they used to know how to do well, versus those who don’t. Are there different outcomes in terms of health or cognitive disability? Or what do we know about that stage? Bryan Kolb: 21:52 Yes, there seems to be. And music is one of the ones that looks like really beneficial later in life. You can buy all these games and so on that are supposed to improve your cognition and later life there’s absolutely zero evidence that, that really generalizes to anything music is one thing that does, probably the only other thing that has as big an effect would be learning a new language, which is like learning music and exercise and the exercise again, because of the increased blood flow in the brain and elsewhere in the body. But those three would probably be the most beneficial ones. Richard Miles: 22:22 One of the insights is it . If you do choose to do something later in life, it sounds like it should be something new, right? Rather than doubling down on a skill that you already have and you decide, well, I’m already a good musician. I’m going to be a better musician or I’m a really good whatever I ski well, or I’m going to do better at it. Does that not challenge the brain as much as if you take up something, even an elementary level that you really don’t know how to do, let’s say learn Chinese or learn to play an instrument that you’ve never picked up before. Is that better exercise or better stimulation for the brain at that age? Bryan Kolb: 22:55 I would think so. As long as you’re engaged with it and not frustrated by it, you will do to some extent obviously, but one of my colleagues was saying, well, he’s been playing the guitar for so long and he plays the same music over and over again. I said, you really need to play new music, brother . It’s a different style of music or different materials playing the same songs over and over again, really , isn’t engaging the brain very much. It’s just a motor skill. It’s , it’s a program that comes out and it’s not really changing anything. Richard Miles: 23:21 Bryan, I always like to ask guests about their background, sort of what influences them. And since we are talking about brain plasticity and education and new experiences, can you tell us a little bit about your growing up, your father worked in the oil industry, right. And your mother was a dancer for a while professional dancer. What was it like growing up? What do you remember your early influences and when do you feel your brain changing? Let’s go with that. Bryan Kolb: 23:47 I’m not sure I felt it changing, but I grew up in Calgary and yeah, my dad was in oil business. He liked to say that he went to the University of Turner Valley and people would , oh yeah I’ve heard of that. Well, Turner Valley was the first big oil field in Canada and he was a rough neck prior to the war. And so he never actually went to university because there was no money. He did extremely well in school. He still had his high school marks and he liked to compare those mine . And I didn’t shine compared to his, my mom was a dancer and she would spend a lot of time sort of dancing around the house. I remember, but she was a house flyer . The thing that I kept hearing was you’re going to be the first person in a family to go to university, which I was. And when I went, I didn’t know what the university really was just more school. And I thought, well, maybe I’ll be a lawyer not realizing what lawyers do, well it sounded okay. As I was finishing my first degree, one of my professors asked me what I was going to do. And I said , I had no idea. And he says , well, why don’t you go to graduate school? I didn’t , you know what that was? So he explained it and he says, come with me. He was the Associate Dean of graduate service. He said, fill this form out. And so I did, and I was accepted at the University of Calgary to do master’s work. And I did it in what, at that time, basically it was in animal behavior that I was studying since I’m pretty dumb in 2020, but the learning ability of squirrels and chipmunks and rats and so on comparing them. My mother was convinced this wasn’t my father, particularly this wasn’t going to be a career. So I had become interested in the fact that these animals were so different. Behaviorally had to be related to their brain . So decided to sort of look doing neuroscience, what we now call neuroscience . It didn’t really exist. Then handed off to Penn State and worked with somebody who was one of the leaders in the field, particularly with respect to the frontal lobe , did my PhD with him. Then I went to University of Western Ontario to do a neurophysiology for two years. And then I went to the Montreal Neurological Institute to study humans with brain injuries, surgically induced brain injuries, which was going back to my PhD kind of stuff. And that’s when I discovered neuropsychology and went, you know, there must be a book on this and I would talk to the graduate students and other postdocs and everybody agreed there wasn’t a book. And there was no such course. So I decided to design a course. And when I moved back to Alberta people in the Mcgill that I was nuts to leave Mcgill and go to this little, very new University (inaudible), but it was not far from where I’d grown up. And I just thought, I want to go home to the mountains. I decided, you know, we really need to write a book. Now I was 28 and you know , 28 year olds don’t start fields. They don’t start writing books in the field, but I didn’t know that. And so I convinced my new colleague in which I had to do it with me. So we wrote this book and the rest was history. We were just finishing the eighth edition, which I think will be the last one, 40 years later. So that’s sort of the nutshell of the educational history. Richard Miles: 26:40 So you were 28 when you wrote the book, meaning your brain wasn’t quite done being developed. So that’s probably right . We wrote the book, right? Bryan is, cause you didn’t know any better, but as you said, one final question, you’ve been a pioneer in this field of neuropsychology . What is sort of the next chapter, which does the field look like now? What are your grad students or your young postdoc fellows? What are they working on? Can you give us a sort of sneak peek of what sort of research we might see coming or being published in the next decade or two? Bryan Kolb: 27:08 Sure. So the biggest change in behavioral neuroscience has been the advances in noninvasive imaging. So MRI functional MRI and all the various variations of this. So historically in order to understand how the human brain work, we studied lab animals and we induced and we still do induce injuries in these animals and then see what happens. We measured electrophysiology and so on, but we couldn’t really do to any noninvasive way. I remember when I was at the MNI in 1975, the first CT scan in Canada was installed and the radiologists were going crazy over this cause they could actually see through the skull. In hindsight, it was pretty crappy because it was new, but now it’s fabulous. The MRI can really make a difference to how we study the brain and functional magnetic resonance energy means that we can see the brain in action online. We can see the blood flow moving one place to another as we’re doing things. And so this has really made a difference. So that’s one big difference going to where I think students are going. One of the things we’re doing is we’re trying to do grand rounds presentation to the pediatric neurologist at the University of Calgary children’s hospital. It was mostly on animal work and they wanted me to come and see the kids in intensive care. And I said, well, what’s the standard of care? What do you do with these kids? And basically they said, well, we cool them down for 24 or 48 hours to reduce the inflammation. And then we hand them to the parents and say, good luck. We can do a lot better than that. We can make a program up is based on our animal studies, trying to work with these kids. So tactile stimulation is huge. So tactile stimulation or animal studies, we’ve shown that tactile stimulation produces profound changes in brain. We can really reverse or reduce the effects of early brain injury , the effects of drugs, all kinds of stuff with tactile circulation. So we have a program that just kinda got messed up a bit with COVID, but we’ll resume doing that. We have another program that students are really interested in applications to indigenous communities, where the early experiences are often not very good. The information about brain plasticity is absent for the moms and the dads. They don’t realize that this serve and return is so crucial to language development and cognitive development. So I think there’ll be more and more of this kind of activity. And I think the use of animals is going to go down in large ways. We can use far fewer animals by using imaging techniques in the animals as well. So these are the changes that we’re going to see. And of course this is flows in humans with noninvasive imaging but one of the things we have to remember is that when you’re looking at the noninvasive imaging, the whole brain seems to be involved in everything, but when you damage the brain, it doesn’t look that way. So we still have to keep studying patients to try and get some sense of what the crucial regions are for particular kinds of coordinating activities. Richard Miles: 30:06 Bryan, that is tremendous research that you’ve done and what you’ve sketched out of what’s coming. And the implications I think are really just enormous across, not just the field of education, but a whole bunch of different fields and will impact a lot of the research that’s going on and the application I want to thank you very much for joining me on the show today and stay safe up there in Calgary and hope we can have you back on the show at some point. Bryan Kolb: 30:27 Thank you it’s been fun. Outro: 30:30 Radio Cade is produced by the Cade Museum for Creativity and Invention located in Gainesville, Florida. Richard Miles is the podcast host and Ellie Thom coordinates inventor interviews, podcasts are recorded at Heartwood Soundstage and edited and mixed by Bob McPeak. The Radio Cade theme song was produced and performed by Tracy Collins and features violinists , Jacob Lawson.

COVID-19, clinical trial processes, pharmaceutical R&D, vaccine development, use of preventative medications, Alzheimer's disease, PTSD After obtaining his medical degree in Belgium in 1972, Pierre Etienne moved to McGill University, where he did postgraduate work in neurochemistry. There he directed a program on the biochemical, physiological, and neuropathological basis of Alzheimer's disease. After a brief passage in experimental medicine at Ciba-Geigy (now Novartis), he went back to McGill in 1987, dividing his time between the Montreal Neurological Institute and the Allan Memorial Institute. In 1989 he joined Pfizer as Director of Experimental Medicine, responsible for all Phase 2 A programs for US and Japan discovered compounds. In 2003, he became CEO of PhageTech, Inc., a privately-held biotechnology company based in Montreal, Canada. PhageTech exploited a proprietary platform based on phage-bacterial intracellular interactions to research and develop new classes of synthetic antibiotics. Phagetech later became Targanta Therapeutics that went public on NASDAQ (TARG) in the summer of 2008. In December 2009, he started a new life as a physician at the Douglas Institute. In July 2011, he was appointed Director of the Clinical Research Division. He is the co-Director of the Alzheimer’s disease prevention program (Stop-AD). --- Send in a voice message: https://anchor.fm/scientificsense/message Support this podcast: https://anchor.fm/scientificsense/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.20.093393v1?rss=1 Authors: emir, u., Sood, J., Chiew, M., Thomas, A., Lane, S. Abstract: Purpose: The human cerebellum has connections to brain systems controlling motor, social, and cognitive function due to the multiple linkages to the forebrain, the thalamus, and the spinal cord. The cerebellum poses many challenges to magnetic resonance spectroscopic imaging (MRSI) due to the caudal location, the susceptibility to physiological artifacts and partial volume artifact due to its complex anatomical structure. Thus, in present study, we propose a high-resolution MRSI acquisition scheme for the cerebellum. Methods: A reduced field of view (FOV) metabolite-cycled full-intensity short echo-time magnetic resonance spectroscopic imaging (MRSI) at 3T with a nominal resolution of 62.5 uL was developed. Single-slice reduced-FOV MRSI data were acquired from the cerebellum of 5 healthy volunteers with an in-plane resolution of 2.5 x 2.5 mm2 in 9 minutes 36 seconds. Spectra were quantified with LCModel. A spatially unbiased atlas template of the cerebellum was used for analyzing metabolite distributions in the cerebellum. Results: Using LCModel analysis, we found that the acquired spectra allowed for the mapping of total N-acetylaspartate, total creatine, total choline, glutamate+glutamine and myo-inositol with CramerRao lower bounds below 50%. A spatially unbiased atlas template of the cerebellum-based region of interest (ROIs) analysis resulted in spatially dependent metabolite distributions in 9 ROIs. The group-averaging across subjects in the Montreal Neurological Institute-152 template space enabled generation of high-quality metabolite maps in the cerebellum. Conclusion: These findings demonstrate that reduced-FOV, zoomed, MRSI can perform robustly on MRI systems and within a clinically feasible acquisition time. Copy rights belong to original authors. Visit the link for more info

Neurosurgeon Dr. Wilder Penfield was born on this day back in 1891. To learn more we spoke with Dr. William Feindel who worked with Dr. Penfield at the Montreal Neurological Institute back in the 1950s.

Trained in computer science and biology, Robert's passion for combining medicine and AI throughout his work and research has grown extraordinarily. As a software developer at the Montreal Neurological Institute, Robert worked on integrating state-of-the-art deep learning techniques in the healthcare industry, specifically brain imaging. As CTO of Aifred Health, in pursuit of better mental health care. Follow his journey on Twitter at: @robert__fratila LinkedIn: https://www.linkedin.com/in/robertfratila/

Are obese people addicted to food? It’s an often proposed idea and something researchers in Montreal investigated Dr Alain Dagher (MD. FRCP) supervised the research team. He is a professor in the department of neurology at the Montreal Neurological Institute… »

While the human brain is hardwired to feel pleasure for basic survival necessities, such as eating and sex, music—although obviously pleasurable—doesn’t offer the same evolutionary advantages.Robert J. Zatorre, Ph.D., talks about his Cerebrum article, “Why Do We Love Music,” (dana.org/Cerebrum/2018/Why_Do_We_Love_Music/) his pioneering research at McGill University’s Montreal Neurological Institute, and research that shows that music has the power to change an individual’s brain.

How can Bruce overcome a fear of pain? Find out on this week's episode of School of Batman! This week, we're joined by Ali Khatibi. Ali has a PhD in Psychology from KU Leuven and is currently a post-doctoral researcher at the Montreal Neurological Institute at McGill University. You can find more about Ali on Twitter at https://twitter.com/AliiKhatibi. __________________ Impact Moderato by Kevin MacLeod is licensed under a Creative Commons Attribution license (creativecommons.org/licenses/by/4.0/) Source: incompetech.com/music/royalty-fre…isrc=USUAN1100618 Artist: incompetech.com/ Cool Vibes - Film Noire by Kevin MacLeod is licensed under a Creative Commons Attribution license (creativecommons.org/licenses/by/4.0/) Source: incompetech.com/music/royalty-fre…isrc=USUAN1100863 Artist: incompetech.com/ Mechanolith by Kevin MacLeod is licensed under a Creative Commons Attribution license (creativecommons.org/licenses/by/4.0/) Source: incompetech.com/music/royalty-fre…isrc=USUAN1100879 Artist: incompetech.com/

Julie Eng, Daniel Zuckerbot and David Peck talk about their new film The Science of Magic, change blindness, assumptions, subverting reality, free will, doubt and the problems of perception. Synopsis Magic has become the latest investigative tool for scientists exploring human cognition, neurobiology, and behaviour. Across Canada, the US and Europe, our film follows researchers who are bringing magicians’ tricks into the laboratory.  With impossible magic, amazing facts, and opportunities for viewers to participate in the magic, this extraordinary exploration peeks behind the curtain into a fascinating world where ancient magic meets modern science.  Canadian magician and executive director of the arts organization Magicana, Julie Eng not only mystifies us with magic, she also takes us to Montreal’s McGill University to meet Jay Olson. He is one of the scientists spearheading this novel and powerful approach to experimental psychology.  On the streets of Montreal Julie and Jay use card tricks to help us understand how magic can be used to explore human consciousness. But these simple tricks have given way to more elaborate experiments. We join Jay at the Montreal Neurological Institute for an extraordinary demonstration involving an MRI machine that can apparently not only read minds but can even use its electromagnetic fields to manipulate your most private thoughts.  Watch the trailer here. Biography Julie Eng is best described as a charming and enchanting performer who is passionate about her craft. Both her peers and her clients consider this award-winning magicienne one of the up-and-coming performers of her generation. Her interest in magic began early; raised in a family of magicians, she has been a stage performer since she was a child. As she earned her Commerce degree, Julie’s true love for the unique art of magic blossomed into a career. And now, for over three decades, Julie has brought her magical expertise to thousands of private functions, festivals, conventions and special events around the globe. Julie is also the executive director of Magicana – an arts organization and registered charity dedicated to the study, exploration and advancement of magic as a performing art. Inside of her work with Magicana, Julie is one of the founding organizers for two unique community outreach programs, My Magic Hands and Senior Sorcery. Julie was also a part of another one of Magicana’s productions, a theatrical show, Piff Paff Poof which was designed specifically to introduce the experience of the theatre to young families.   Over the years, Julie has developed a refreshing and distinctive style – a mix of elegance, surprise and humour – that has made her a popular entertainment choice. Whether on stage or mingling with her audience, Julie’s magic is distinguished by her dexterous skill, confident presentation and professional manner. Julie has also received accolades from her fellow magicians, who have invited her to perform at magic conventions across North America. She has been featured in, MAGIC, Genii and The Linking Ring, internationally distributed trade magazine. Julie’s energetic performances are well suited to a multitude of venues: corporate receptions, trade shows and product launches, hospitality suites, conventions and client appreciation and development events. Julie’s style, charm and repertoire have consistently garnered high praise from her clients, including some of the largest and most creative companies in Canada and the United States. Daniel Zuckerbort’s first experience in the Canadian film industry was in 1974 when, while studying history of science, religion and philosophy at the University of Waterloo, he got a summer job as a researcher for a documentary. Though only 20 at the time this was far from his earliest foray into the Canadian art scene. At the age of 15 he began working as an assistant in the technical crew at Theatre Passe Muraille. This was in 1969 and Passe Muraille was the centre of avante garde theatre. In recent years Daniel’s specifically theatre related work has been limited to directing actors in some of his productions as well as having made a number of documentaries about performers. A working magician himself for some years, he taught magic privately and for the Toronto Board of Education. He is also one of the founding board member of Magicana a registered charity dedicated to the exploration of magic as a performing art and to increasing the public’s understanding and appreciation of this art. For more information see www.magicana.com From the early 80s, through much of the 90s he was also involved managing the organization and activities of large groups of volunteers. These activities included helping organize neighborhood newspapers in Canada and abroad (including England, Scotland, Iceland, and Jamaica). Daniel is fluent in Spanish. His interests in the history of technology have come to a happy meeting in his current experiments in textile production, dye chemistry and casting metal (copper, bronze, brass, and iron) using kilns and crucibles that he has built himself. His creative endeavors are not limited to film or the forge. He is a writer in a range of genres and one of his short writings was published in the Spring 2011 edition of the literary journal Descant. ---------- Image Copyright: Julie Eng and Daniel Zuckerbot and Reel Time Images. Used with permission. For more information about his podcasting, writing and public speaking please visit his site here. With thanks to producer Josh Snethlage and Mixed Media Sound. See acast.com/privacy for privacy and opt-out information.

Rob connects with Wayne Sossin PhD, of the Sossin Lab at the Montreal Neurological Institute and Hospital at McGill University, who is researching how memories could be scrubbed from the brain to treat things like PTSD

In the news this week, the launch of NeuroCDRD – a new initiative to accelerate development of treatments for neuro diseases; OICR researchers invent a new molecular barcode technology; and Aurinia Phramceuticals prices a US$150.5 million public offering of common shares. We have all this and more coming up on Biotechnology Focus Radio. Story 1 Our first story this week highlights Calgary, AB’s Oncolytics Biotech® Inc. The company has entered into a collaborative research project  with cancer charity Myeloma UK and multi-national biotech firm, Celgene.  In the joint initiative Myeloma UK has launched MUK eleven, a first-of-its-kind immunotherapy trial that aims to modulate the immune system to target myeloma. The Phase 1b trial will study Oncolytics immuno-viral therapy and lead product REOLYSIN®, in combination with Celgene Corporation's immunomodulatory drugs (IMiDs), Imnovid® (pomalidomide) or Revlimid® (lenalidomide), as a rescue treatment in relapsing myeloma patients. MUK eleven’s chief investigator Gordon Cook, Consultant Haematologist at Leeds Teaching Hospitals Trust  says this trial is about taking a new approach of activating a patient's own immune system to target their myeloma (immunotherapy) using a natural virus and lenalidomide or pomalidomide. REOLYSIN will be combined with Celgene's Imnovid® or Revlimid® in patients whose myeloma is progressing while on these IMiD treatments. The dose escalation trial will look at the safety and tolerability of these combinations, and will investigate whether the addition of REOLYSIN extends disease control in this patient group. This clinical study expands on earlier pre-clinical work by Professor Cook that demonstrated that REOLYSIN has dual modes of action against multiple myeloma; being both directly cytotoxic and also activating immune effector cells to target and destroy cancer cells. Further, this immune-mediated activity can be enhanced by immunomodulatory agents to eliminate disease. The trial will aim to recruit 44 patients across up to six Myeloma UK Clinical Trial Network centres in the UK. MUK eleven is part of the Myeloma UK Clinical Trial Network, a portfolio of early stage trials coordinated by the Clinical Trials Research Unit at the University of Leeds, focused on testing and speeding up access to promising new treatments for patients. Story 2 In a unique public-private partnership, Montreal’s Cyclenium Pharma Inc. and Toronto’s Hospital for Sick Children (SickKids) have entered into a research agreement designed to facilitate the discovery of novel modulators for multiple new and existing biological targets of pharmacological interest across a variety of disease areas, including cardiovascular, immunology and oncology.  Cylenium is a company focused on discovery and development of novel drug candidates through the use of its proprietary macrocyclic chemistry. The collaboration will give SickKids researchers immediate access to the company’s QUEST Library™ of next generation macrocyclic molecules and associated chemical hit and lead optimization capabilities. The initial objective of the partnership is to identify compounds capable of interacting with specific therapeutic targets being studied at SickKids, thereby providing tools to improve the understanding of their involvement in the pathophysiology of specific diseases, with the ultimate goal of discovering novel therapeutic or diagnostic agents. Cyclenium president, CSO and CEO Dr. Helmut Thomas.adds that his company’s library will be made available to researchers through the SickKids Proteomics, Analytics, Robotics & Chemical Biology Centre (SPARC BioCentre). The SPARC BioCentre is a high-throughput drug screening facility at SickKids. One of the first studies to be initiated involves targets implicated for the treatment of cancer and immune disorders. For Cyclenium, this is the latest in an extensive series of international discovery collaborations established with prominent companies and research institutions to explore the exciting potential of its unique macrocycle chemistry technology, including Astellas Pharma, Haplogen GmbH, Fundación MEDINA, German Cancer Research Center (DKFZ), McGill University/Goodman Cancer Research Centre, Institute for Research in Immunology and Cancer (IRIC)/Université de Montréal, and Southern Research Institute. Story 3 Clinical-stage drug developer Aurinia Pharmaceuticals last week announced the pricing of secondary public offering for gross proceeds of approximately $150.5 million US. As part of the offereing the company is selling 22.3 million shares at $6.75 per share. Leerink Partners LLC and Cantor Fitzgerald & Co. are acting as joint book-running managers for the Offering, that is expected to close March 20th. The cash will be very beneficial as the Victoria-based company intends to initiate a Phase 3 trial for its lead drug candidate, voclosporin, in treating lupus nephritis. The trial will commence in the second quarter. The drug successfully went through a positive 48-week data phase 2b trial in 2016 and 2017, and seems on track to becoming the first drug to demonstrate a clear benefit for the disease. As an aside, Aurinia’s stock had hit an all-time high of $10.50 per share on March 13, the eve of the public offering announcement. By offering its shares at $6.75 the next day, new investors received a 36 percent discount. Canada’s Motley Fool reported that while it may seem as if investors are getting a raw deal, it should be noted that the stock began 2017 at just $2 per share. Motley Fool further commented that there are only 53.45 million shares outstanding today, and the company ended 2016 with less than $40 million in cash. In other words, while the number of shares will be diluted by 41.7%, the company will more than quadruple its cash. Story 4 In Toronto,  a team of cancer researchers have identified a protein biomarker expressed on the surface of tumour cells in high-grade serous ovarian cancer, the most common and lethal subtype of the disease. The findings, featured on the cover of the March 7 issue of Cell Reports, show that patients with high levels of the biomarker, CD151, have a poor prognosis, says lead author Mauricio Medrano, a molecular biologist and research associate at Princess Margaret Cancer Centre, University Health Network. “Ovarian cancer is many diseases,” says Dr. Medrano. “By identifying CD151 and its underlying role in cancer cell survival, we hope to develop a therapy to target it. As a marker for poor prognosis, with further research, there is the potential to develop a clinical screening tool to help personalize cancer treatment for patients.” The research was led by principal investigator Dr. Robert Rottapel, senior scientist and Professor, Departments of Medical Biophysics and Immunology, University of Toronto. In lab experiments, the research team used cell lines derived from 40 patient tumour samples to identify that CD151 contributes to the survival of cells of high-grade serous ovarian cancer origin. The team further analysed tissue samples from a cohort of approximately 1,000 patients to establish the correlation of high levels of CD151 to poor prognosis. Dr. Medrano says the study provides a lot of new information about other possible targets, not only CD151, that could be important and can provide new ideas for how to target ovarian cancer.” The research was supported by the Ontario Institute for Cancer Research, Ovarian Cancer Canada, the Canadian Ovarian Cancer Research Consortium’s biobank funded by the Terry Fox Research Institute, and The Princess Margaret Cancer Foundation. Story 5 Also In Toronto, Researchers at the Ontario Institute for Cancer Research (OICR), together with international collaborators, have invented a technique to avoid a major problem with common laboratory techniques and improve the sensitivity of important cancer tests. The findings, recently published in the journal Nature Protocols, describe a process by which the sensitivity of DNA sequencing can be improved. The technology, called SiMSen-Seq, could aid in detecting the recurrence of cancers, catching possible disease relapses faster than current methods and improving patient outcomes. Essentially the scientists have created a DNA barcode with a hairpin structure that as Dr. Paul Krzyzanowski, Program Manager of OICR’s Genome Technologies Program explains opens up to be read when heated and contracts when cooled. This allows researchers to ‘hide’ the barcode and analyze more patient DNA fragments in a single reaction he says. Cirrently, for DNA sequencing, scientists often use a technique called polymerase chain reaction (PCR) to increase the amount of DNA available from a sample. However, PCR can introduce mistakes that can limit researchers’ ability to detect real mutations in the original DNA molecules. To track the original molecules in a sample, molecular tags called DNA barcodes are added. This technique is essential for sensitive detection of mutations but can lead to other errors, as components of the tags can interfere with each other and affect the final results. Dr. Krzyzanowski led the development of analysis pipeline software used in SiMSen-Seq which flags errors in sequencing results and corrects them computationally. Current genome sequencing technologies return results with error rates of about one per cent, meaning that for researchers to be certain that a mutation exists it has to be detected in a sample at a rate of greater than one per cent. Dr. Krzyanowski says that the SimSen-Seq technology has lowered this error rate 100-fold, meaning that the recurrence of cancers could be detected at lower levels and earlier than before, allowing patients to receive additional treatment sooner. His team has already patented the technique, and while it can conceivably be performed in any molecular biology lab, the group also hopes to make their expertise in using the method available to the research community. Those interested in accessing this service can do so through OICR’s Collaborative Research Resources directory. Story 6 In our final story, three leading players in Canada’s health sciences sector are joining forces to create a novel drug development platform that will help advance new therapeutics for some of the most debilitating conditions such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and Parkinson’s disease. The initiative, under the banner of ‘NeuroCDRD’, is jointly led by The Centre for Drug Research and Development (CDRD), the Montreal Neurological Institute and Hospital at McGill University (MNI), and Merck. Its initial focus is the creation of a high-content hiPSC (human-induced pluripotent stem cell) screening platform that will help researchers better model neurological disease. Development of new drugs for neurological diseases has long been hampered by the lack of predictive humanized models, and many treatments that have looked promising in animal studies have in turn failed in subsequent human clinical trials. To mitigate this challenge, this new collaboration will use the MNI’s renowned hiPSC platform and bring together experts from MNI’s neurological and CDRD’s drug screening and assay development teams to develop a new generation of disease-specific research models using patient-derived hiPSCs. The idea is to significantly reduce research timelines and costs, making it possible to develop future hiPSC models for neurological diseases with smaller patient populations. As Gordon McCauley, President and CEO of CDRD explains this collaborative initiative not only combines the cutting-edge science of academia, that it will also benefit from CDRD’s translational abilities, and the commercial resources of a top industry partner like Merck. “By working together, we are a catalyst for Canadian life sciences leading the world,” he said. And that wraps up another weekly episode of the Biotechnology Focus RADIO. A special shout out to Laskey Hart who works tirelessly to produce each weeks show, and to the Biotechnology Focus research team for tracking this weeks stories.  As we’re always on the lookout for your story ideas and podcast suggestions we’d love to hear from you our listeners, to let us know what’s hot on the Canadian biotech scene.  Be sure reach out to us via twitter @biotechfocus, or by email at  press@promotivemedia.ca with your suggestions. And of course, you can also catch up on past episodes online via our podcast portal at www.biotechnologyfocus.ca .

On this weeks show, and amazing turnaround in the fortunes of the MaRS West Tower, CQDM and Brain Canada team up once again, and a significant step in the fight against cancer. We have all this and more on this week’s Biotechnology Focus Radio Show Podcast. Welcome to another episode of Biotechnology Focus Podcast. I’m your host Shawn Lawrence, here to give you a rundown of this week’s top stories on the Canadian biotech scene,   Story CQDM and Brain Canada are join forces again in the funding of two new research projects to address unmet needs in brain research. Together, the two organizations are awarding a total of $3 million to the projects which will oversee the development  cutting-edge tools, technologies and platforms designed to accelerate the discovery of new drugs for brain and nervous system disorders. The two distinguished research teams will unite nine researchers from seven public and private organizations across Canada. The first project is led by Edward Fon at the Montreal Neurological Institute and Hospital (MNI) joined by multi-provincial collaborators from McGill University, Université Laval and University of British Columbia. The second project led by Jean-Martin Beaulieu at University of Toronto is a public-private collaboration with the Research Institute of the McGill University Health Centre and ImStar Therapeutics in Vancouver. Additionally, these researchers will benefit from CQDM’s unique mentoring program. They will have the opportunity to collaborate with influential senior scientists from the pharmaceutical industry who bring expertise and support to the projects, to help better align research with the needs of industry and patients. The Brain Canada funds are provided through a partnership with Health Canada, known as the Canada Brain Research Fund. Story Princess Margaret Cancer Centre scientists have discovered a distinct cell population in tumours that inhibits the body’s immune response to fight cancer. According to principal investigator Pamela Ohashi, director, Tumour Immunotherapy Program at the cancer centre, University Health Network. Dr. Ohashi holds a Canada Research chair in Autoimmunity and Tumour Immunity, the findings, published online in Nature Medicine, are critical to understanding more about why patients will or will not respond to immune therapies.  Specifically, Dr. Ohashi and her team uncovered a potential new approach to modulate the immune response to cancer. She adds that by looking at tumour biology from this different perspective, researchers will have a better understanding of the barriers that prevent a strong immune response. This can help advance drug development to target these barriers. Dr. Ohashi discusses her team’s discovery of a new population of cells that regulate immune response in the following audio clip. https://www.youtube.com/watch?v=l-vbE-DRTdY Dr. Ohashi’s research team along with international collaborators analyzed more than 100 patient samples from ovarian and other cancer types to discover a distinct population of cells found in some tumours. This population of cells suppresses the growth of cancer-fighting immune cells, thereby limiting the ability of the immune system to fight off cancer. For patients, down the road Dr. Ohashi envisions a new era of combined therapies to simultaneously target and kill these suppressive cells while augmenting the immune response against cancer.  The team’s next avenue of research will be focused on identifying a “biomarker” that can identify this distinct suppressive cell elsewhere in the body – for example, in blood or other samples – as a potential predictive clinical tool to determine when these cells are present in patients, which currently cannot be done. Dr. Ohashi’s research was funded by the Canadian Institutes of Health Research and The Princess Margaret Cancer Foundation. Story Aequus Pharmaceuticals has landed $100,000 in federal funding through the National Research Council’s Industrial Research Assistance Program. The company plans to use funds towards an ongoing proof-of-concept clinical study for its lead product candidate, AQS1301, a once-weekly transdermal aripiprazole patch. Aripiprazole is an atypical antipsychotic and the active ingredient in Abilify®, a leading medication in the U.S. used for the treatment of a number of psychiatric disorders including bipolar I disorder, schizophrenia, major depressive disorder and irritability associated with autistic disorder. Aripiprazole is currently available in once-daily oral tablets and a once-monthly injectable form, however, medication adherence continues to be a significant challenge for patients. Offering the medication in a patch form potentially could make it more convenient to use, and improve patient adherence says Anne Stevens, COO and director of Aequus Pharmaceuticals . The product is currently in clinical development, butAequus expects to confirm its regulatory development plan in a pre-Investigational New Drug (pre-IND) meeting with the US Food and Drug Administration (FDA) in the second half of 2017. Aequus anticipates results of the current repeat dose, 28-day study in the first quarter of 2017. The results will be used to inform the final design of the patch to be advanced into the regulatory phase of its clinical trials. Story Genome British Columbia is making an investment into Augurex Life Sciences through its Industry Innovation (I²) funding program. The company was founded on an invention shared between the University of Alberta and the University of British Columbia in 2006. The funding is repayable and is allocated to promising technologies (products, processes or services) at the early stages of commercial development, and aims to provide risk capital that is concurrently matched by other public or private funding sources. The investment will go towards helping the company launch several blood test products from its pipeline and advance its overall therapeutic program. With a focus on autoimmune diseases affecting joints such as rheumatoid arthritis (RA), Augurex has already developed its first blood test, called JOINTstat™, which measures the 14-3-3η(eta) protein in blood for early RA diagnosis, joint damage risk monitoring, and also predicts RA development in people with joint pain. Since this is a very early contributor to disease and correlates with joint damage prognosis, it facilitates the identification of patients for early RA intervention and tighter control of treatment so that clinical and remission targets can be reached; the highest priorities in rheumatology care. Additionally, a portfolio of 14-3-3η-centric biomarkers has emerged from Augurex’s work, with demonstrated applications in multiple autoimmune diseases with joint involvement. As an aside, JOINTstat has since been studied in over 4,000 patients, and is Health Canada approved. It was launched in Canada by LifeLabs and has been in clinical use since late 2013 in the U.S. Recently, the test was also CE marked and TGA approved making it certified for clinical use in Europe and Australia.  Story California Capital Equity, LLC, has increased its equity position in Laval, QC’s ProMetic Life Sciences, exercising 44,791,488 share purchase warrants at a price of $0.47 per share for total proceeds of $21,051,999.36. The venture capital firm  based in LosAngeles, CA, specializes in providing growth and development capital to start-up through mezzanine stages. The firm’s equity and debt investments are typically in small and medium sized companies. It first invested in ProMetic in 2008. Dr. Patrick Soon-Shiong, CEO of California Capital Equity cited the company’s robust proprietary therapeutic platforms and promising growth potential as key factors behind the firm’s latest investment.  Story Our final story this week, In an amazing turnaround for what once was a struggling center for innovation and entrepreneurship, that once upon a time event required the government of Ontario to step in and offer bridge financing to keep it afloat, MaRS Discovery District now reports that it has completed a significant private financing of its West Tower, with proceeds of this transaction to be used to repay most of the Ontario government's interest-bearing loans to MaRS. The caveat, is the repayment comes almost three years ahead of schedule.  Taking part in the private financing are Manulife, Sun Life Financial and iA Financial Group, who together led the $290-million transaction by investing in 19-year bonds issued by Phase II Investment Trust. According to Ilse Treurnicht, CEO of MaRS, the West Tower is now fully leased, and could soon generate the operating income required to be entirely self-sustaining, putting MaRS on stable footing. Last year we featured two of the more noteworthy tenants at the building, Johnson & Johnson’s JLABS @ Toronto, and the Bridge@CCRM in our June/July issue of Biotechnology Focus. And now, offering over 1.5 million square feet of state-of-the-art lab and office space in the heart of Toronto's Discovery District, the MaRS Centre is now home to more than 140 research labs and companies spanning the entire innovation ecosystem, including Multinational medical firms such as Johnson & Johnson's JLABS @ Toronto, which itself houses over 40 biotech and health startups, Merck, growing  life science firms such as Synaptive Medical, Deep Genomics, Interface Biologics, Highland Therapeutics, and Triphase Accelerator; and life science incubators like Blueline Bioscience. Leading research groups from the University of Toronto (which owns a 20% stake in the West Tower), University Health Network (including Princess Margaret Cancer Centre), Ryerson University and the Ontario Institute for Cancer Research also call the West tower home. The facility has even attracted other major tenants like Autodesk, Facebook, Merck, PayPal, Etsy, Airbnb, IBM, CIBC and RBC. In all, ventures within the MaRS network raised $2.6 billion in capital and generated $1.3 billion in revenue between 2008 and 2015, and today employs more than 5,200 people. Well that wraps up another episode of the Biotechnology Focus Podcast. We hope you enjoyed it. Be sure to let us know what you think, and we’re also always looking for story ideas and suggestions for future shows, and of course we’d love to hear from you as well, simply reach out to us via twitter @biotechfocus, or by email at the following email address  press@promotivemedia.ca. And remember, you can also listen to past episodes online via our podcast portal at www.biotechnologyfocus.ca . For all of us here at Biotechnology Focus, thanks for listening.

It’s that time of year again, when you’ve got the urge to get close to that special someone, light some candles, and put on the latest OYM episode for a night of sweet, sweet neuroscience.  And this year, we’re delighted to welcome our official valentine, Daniel Almeida, to the guest host chair.  He’s a Master’s student who’s excited about developing a new microscopy technique in his lab, and is putting his background in sex research to good use with this week’s paper about oxytocin and sexual behavior in Prairie Voles.  But first, we’ve got some local neuroscience news to discuss.  The Montreal Neurological Institute in Montreal has announced a new plan to promote open science by asking it’s researchers to make all data and programs available and no longer supporting the creation of new patents. We’re also talking about reproducibility again, with the launch of a the new F1000 research channel, thePreclinical Reproducibility and Robustness Channel, and a comment piece in Science that highlights the many hurdles involved in the ‘self-correcting’ aspect of science.

Elevate your Mind   A study at the Montreal Neurological Institute at McGill University suggests that listening to music "can arouse feelings of euphoria and craving," even stimulating dopamine release in the brain — a chemical affiliated strongly with pleasure, reward and even addiction. Not that I needed the emprical data set to believe it, but countless studies do show that music has a LASTING impact on the brain plasticity.. There you go... save yourself a session and treat your brain to some free therapy :) Semi-chilled, slightly dark, resolutely progressive set.. Musical food for your brain cells. Find the right setting, load the set up and let your brain do the rest..   In many a way, where classical meets electronica.. Set got scratchy towards the final tracks.. It happens.. Pesky downbeats...   Playlist:     2015 The Bridge (Shur-I-Kan Remix. vs Original Mix). Jody Wisternoff feat. Sian Evans 2014 Till I Come (Nick Devon & Inner Rebels Remix). Chris Karpas, Mass Digital 2010 Aegean Sea (Nikos Diamantopoulos Remix). G-Pal 2014 Summer Fun (Slam Duck Remix). RDUO         2013 Divine (Vincenzo Remix). The Saint Petersburg Disco Spin Club, Eleonora 2014 Till I Come (Original Mix). Chris Karpas, Mass Digital 2015 Every Single Piece (Original Mix). Redondo, Bolier feat. She Keeps Bees 2014 Waves (Robin Schulz Remix). Mr. Probz 2014 Click, Search (Jody Wisternoff Remix). Danalog 2014 Walk With Me (Original Mix). Jetlag feat. Esther 2014 The Sin (Original Mix). Bee Hunter 2014 Golden Sky (Sons of Maria Remix). Passenger 10, feat. Lika Morgan 2005 Lost Soul (Afterlife New Mix). Bliss   Highlights: "The Bridge" from Jody Wisternoff popped out a few weeks ago in Matt Darey, Chicane and even Pete Tong top ten. Perfect blend of progressive and classical. Love the track so much that you are getting a double dose.. Beautiful just beautiful "Till I Come": appearing twice (at lest you know the set is unedited and exactly as it came out of the mixer).. Needed the first remix to set the darkish nocturnal mood and the second one because it is perfectly produced. And yes the smal vocal sample is from the ATB classic.. "Aegean Sea" from Nikos Diamontopoulos. Very fine, very stuble work from an immense producers. This is a headphone track, so intricate it is.. "Summer Fun" old trancy feel, almost Moroderesque.. "Divine" from Russian producers SPDSC.. at the crossroads of progressive and nu disco.. because it was time to introduce some vocal (albe it dubbed). "Every Single Piece" from Redondo and Mr. Probz summer anthem "Waves".. when I first heard "Every Piece" I knew it needed to feature side by side with Waves.. Love the production and the "lightness" of it all.. Out of the darker side, into the dim light :) Another Jody Wisternoff tune with Click, Search.. The english born producer, half of the Way Out West outfit, is one out the most talented producers and songwriter of the 21st century progressive scene. "Walk with Me" from Jetlag Prod. (Belgium).. New on the Anjunadeep label as the vibe wrote "this is how commercial house music should sound. Provocative, thoughtful but most importantly – good". "The Sin" from Bee Hunter.. A tactfully produced progressive/trancy production, light and right in the vibe I was going for.. "Golden Sky" nice indie track with a massive remix from the Sons of Maria.. Just yum! Vocalist is Lika Morgan, can't wait to hear more from her. Wanted to finish the loop on a semi-classical track, hence dag up "Lost Soul" one of my favourite chill out tune.. Bliss from Bliss! I hope ( I know) I served you a very good selection of tracks with just so so mixing at times.. This one fell straight from the mixer and it looks I have much more in a similar vibe to come.   A bientôt mes amis.     Xtian        

Denise Klein PhD, of the Montreal Neurological Institute talks about the different interests to be covered at the upcoming symposium on Biligualism and the Brain.

[intro music]   Host – Dan Keller Hello, happy new year, and welcome to Episode Twenty-Six of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Tim Kennedy about remyelination and neural development. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   According to a new clinical trial, azathioprine, or AZA, may be as effective as interferon beta. The generic immunosuppressant was effective in both reducing relapses and reducing new brain lesions in the multicenter trial. This may not be surprising since the drug has been used off-label to treat MS for several decades. If trials continue to go well, AZA may become the go-to alternative for patients who can’t afford brand name interferons.   A pair of Canadian studies recently showed that both neurodegeneration and inflammation may start in the early stages of pediatric multiple sclerosis. One team found epitope spreading in the blood of children shortly after the onset of MS, suggesting a potential new diagnostic tool. Though children comprise only 2 to 10 percent of the MS population, data gleaned from them may provide insights into the disease as a whole.   If you enjoyed our end-of-the-year interview with Alan Alda and find MSDF to be helpful, please consider supporting us with a donation. We share Mr. Alda’s philosophy that closing the gaps between scientific disciplines is key to improving scientific progress. To make a donation, visit msdiscovery.org and click on the green “Support MSDF” button next to “Research Resources”.   [transition music]   Now to the interview. Tim Kennedy is a researcher at the Montreal Neurological Institute. He met with MSDF to talk about the role of certain molecules and receptors necessary for oligodendrocyte development, maintenance, and function and their implications for remyelination.   Interviewer – Dan Keller Welcome, Dr. Kennedy. Let's talk about the life of oligodendrocytes. These are important for myelination and probably play a role in remyelination. What is the life of an oligodendrocyte? How does it start out? And what does it react to?   Interviewee – Tim Kennedy Many labs around the world have been studying the life history of an oligodendrocyte and also the lineage of the cells and how they differentiate during normal development. One of the reasons for doing this is that oligodendrocyte precursor cells are present in the mature nervous system and almost certainly contribute to remyelination in demyelinating diseases like MS. Oligodendrocyte precursors are born in the early embryonic CNS, and from the very restricted regions where they're born they then migrate away to populate all of the regions of the mature CNS where myelin occurs. In the lab here, we've been very interested in the molecular cues that direct and influence oligodendrocyte precursor migration. These include a family of proteins called netrins that we work on. And receptors for netrin like a protein called DCC. DCC stands for deleted in colorectal cancer. It was originally identified in cancer, and we now know that it has a critical role in the central nervous system in the migration, maturation, and maintenance of myelin by mature oligodendrocytes.   MSDF Some of these molecules take on different functions as the oligodendrocytes mature. How do they react, or what do these molecules do over time?   Dr. Kennedy When an oligodendrocyte precursor is born, it makes the netrin receptor DCC, but it doesn't make netrin. What the cell does is it responds to netrin in the environment, and through DCC reacts to it, and the netrin directs the cells to migrate. It tells them to initially migrate away from the position where they're born and sends them in the direction of axon tracks that require myelination. In mature myelinating oligodendrocytes, one of the huge surprises we had is that both of these proteins are made. Now, both netrin and DCC are required for normal neural development. If we examine a conventional knockout mouse that lacks either netrin-1 or DCC, those mice die within a few hours of being born, and there's a massive disorganization of the nervous system. So these are essential for normal neural development. When we look at the mature nervous system, we see that every single oligodendrocyte, every single mature myelination oligodendrocyte, makes readily detectable levels of netrin-1 and also the receptor for netrin-1, DCC. And a very simple statement of the question that we wanted to answer is what's the point of that? Why do these cells make these proteins that are essential for normal neural development but make them in the adult nervous system? In every adult human that we encounter, every single person, we're making netrin-1 and DCC in our brains right now. So what's the point? One of the functions that we've recently identified is that DCC produced by oligodendrocytes is required for the maintenance of myelin. Now what that means is that initially when we looked at the distribution of netrin-1 and DCC in relation to myelin we see that they're enriched at paranodal junctions. Paranodes are at the ends of internodes that are the regions of compact myelin that wrap and insulate an axon. The paranodes are a specialization that's made by the oligo that then connects it and ties it down to the surface of the axon. The paranodes flank the node of Ranvier, which is the key point, the specialized region along an axon that regenerates the action potential. So if we think of the internode of compact myelin as the region where the oligodendrocyte insulates the axon and allows the action potential to jump from node to node, the paranodes are the specializations at the end that tie it down. Now, the paranode is where we see the netrin and DCC enriched. If we take away either netrin-1 or DCC from oligodendrocytes, what we see is that the paranodes begin to come apart. Now in a very recent publication, what we did was use a genetic trick called cre-lox recombination to selectively take DCC out of mature myelinating oligodendrocytes. In these mice, the mice develop perfectly normally, the nervous system develops normally, the myelin develops normally. But then, at two months of age, we induce the deletion of DCC only from oligodendrocytes. Now having taken DCC out of oligodendrocytes, what we see is that first the paranodal junctions start to come apart, and then as we let the mice age the compact myelin itself starts to become disorganized. Now, that's interesting because what we're able to document in these mice is a progressive disorganization of the myelin produced by the oligodendrocyte. The progression is interesting, obviously, because we believe that this has identified a new mechanism that maintains myelin, and we would then relate that to the progression of demyelinating disorders like multiple sclerosis. A consequence of having lost DCC is that the action potential conduction velocity in the nervous system is delayed, and when we look at the mice themselves – and look at their behavior, put them through behavioral tests – what we see is that they become uncoordinated and slower in their movements. So again, this would all be consistent with this disruption of the myelin along the axons in the central nervous system due to the loss of DCC. And it's an indication that DCC being made by oligodendrocytes is absolutely essential to maintain the appropriate organization of myelin.   MSDF That explains why myelin may become disorganized. Now, if there is a state in which it's already disorganized, which we look at someone with MS, is there any indication here how to remyelinate knowing what you now know about what's required for maintenance of myelin?   Dr. Kennedy Certainly. What's really exciting having found that DCC is essential to maintain myelin is that this is a new biochemical mechanism that is required to organize and maintain the structural paranodal junctions, and that that's critical for the integrity and the maintenance of compact myelin. Now, DCC is a transmembrane receptor, and every single component of the signal transduction pathway downstream of DCC is potentially a drug target that could be manipulated to enhance the maintenance of myelin. So this is a new biochemical mechanism that exists in oligodendrocytes that promotes myelin maintenance. And that has enormous potential for trying to encourage the persistence of myelin in demyelinating disease.   MSDF What about remyelination? I think you've said oligodendrocytes are born to myelinate. What's stopping them?   Dr. Kennedy If we go back to the oligodendrocyte precursor in early development, what our studies of the developing nervous demonstrated was that oligodendrocyte precursors are repelled by netrin-1. The normal function of netrin-1 in the early embryo is to drive oligodendrocyte precursors away from where they're born so that they can go out into the rest of the central nervous system, find axons that need to be myelinated and myelinate them. That indicates that in the early embryo netrin-1 is a repellent for these cells. Again, we recently reported that in human MS plaques netrin-1 is present in those plaques. Where that's likely coming from is from the wreckage of cells that have died in those plaques. So I had said that mature myelinating oligodendrocytes express netrin-1. When those cells die and when the myelin is lost, the debris from those cells remains behind and potentially even builds up in plaques. There are a number of inhibitors of oligodendrocyte precursor migration that we now know are present in human MS plaques. These include proteins like chondroitin sulfate proteoglycans, semaphorins, and now netrin. What that strongly suggests is that when oligodendrocyte precursors are migrating in the adult brain to sites of demyelination with the intention of remyelinating an axon that has been demyelinated these inhibitors will very likely prevent those cells from entering the plaque and doing what they were born to do, which is to remyelinate. A very exciting thing about MS research today is that we know that the brain contains stem cells that produce oligodendrocyte precursor cells that readily give birth to these cells. So all of us have oligodendrocyte precursor cells in our head. Those cells are born to myelinate. They will migrate towards plaques where demyelination has happened, and if they're allowed to enter the plaque find the axon that needs to be remyelinated. And if they can be encouraged to overcome whatever it is that is blocking them from remyelinating, potentially that aspect of MS remyelination could be encouraged to happen.   MSDF Do you have some ideas on how to overcome this blockage either clearing away the debris or making the oligodendrocytes insensitive to the inhibitors and the debris?   Dr. Kennedy Both of those approaches would be very appropriate. So encouraging the nervous system to clear away the debris we would predict that that would encourage remyelination to happen. In addition, although I said there were multiple inhibitors present in MS plaques – and those inhibitors have different receptors – downstream of those receptors it's very likely that common signal transduction mechanisms are engaged. So targeting those common signal transduction mechanisms inside the migrating oligodendrocyte precursor cell could very potentially nullify all of the inhibitors at once. If it was possible to turn off the sensitivity to those inhibitors, then we would predict that the cells would enter the plaque more readily, and more of the cells would then be able to encounter the axons that require remyelination, and we would obviously predict that that would promote remyelination happening.   MSDF What are some of the big questions now to look at, solve?   Dr. Kennedy The oligodendrocyte is an absolutely fascinating cell type. It's a highly specialized cell type, critically clinically important. We still understand very little about these cells. The mechanisms that I've been talking about that regulate the maintenance of myelin, those have only very recently been discovered. And I think it's extremely exciting that this type of thing is being found in oligodendrocytes. But these are still very mysterious cell types. I think the more we understand about the cell biology of the oligo the more we'll be able to target pathways in the biochemistry of oligodendrocytes to try and promote things like myelin maintenance and the ability to remyelinate. Being able to do those things and essentially manipulate these cells in specific ways, we can then overcome specific clinical issues.   MSDF Does this go beyond MS? Are there other conditions that it applies to?   Dr. Kennedy I think there are two things built into that question. One is that there are many diseases for which the cause either isn't clear – and MS would be in that category – or there are also diseases that have many different causes, but they may manifest in similar ways. So by understanding oligodendrocytes and being able to encourage oligodendrocytes to remyelinate, that could have broad applicability for treating the symptoms of many different forms of demyelinating disease irrespective of the cause of those diseases. Beyond that, as we come to better understand how cells move in the nervous system, how they migrate, how they form attachments, how they connect to each other, and how they maintain those connections, those kinds of insights are going to have broad applicability for all sorts of neurodegenerative diseases where the basic problem in the neurodegenerative disease is that the networks that are the nervous system are coming apart. And if we can encourage those networks to just stay together or rebuild themselves, then I think that again has broad applicability to many types of neurodegenerative diseases in the myelinating field and outside of myelination, as well.   MSDF It sounds like it may even have applicability to not only neurodegeneration but in development where you may have miswiring such as potentially an autism or something like that.   Dr. Kennedy Yeah. An exciting thing is that a lot of the mechanisms that I'm thinking about and we're thinking about in the lab is that the insights that got us working on myelin, that brought us to work on myelin really came from neural development and better understanding neural development; the studies of neural development identified proteins and gene families that have very, very potent actions in the nervous system. When we then looked at expression, we saw that they were expressed in the mature CNS, and that brought forth a whole other group of questions related to the function of the normal adult nervous system and also the degeneration of the adult nervous system in neurodegenerative disease. The exciting thing about that is that as we understand the molecular biology of the central nervous system better that's going to be applicable to development, to normal function, to enhanced function, and also promoting function in degenerative conditions.   MSDF I appreciate it. Thank you.   Dr. Kennedy You're very welcome.   [transition music]   Thank you for listening to Episode Twenty-Five of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]          

[intro music]   Host – Dan Keller Hello, and welcome to Episode Nineteen of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features the second half of an interview with Dr. Samuel Ludwin. This time Dr. Ludwin and I discuss the implications of treating multiple sclerosis subtypes. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   This week we reported some good news: a large case-controlled study showed that there is no causal link between vaccines and multiple sclerosis. However, the study came with the caveat that there is some increased risk for developing MS in younger patients who receive vaccines. This increased risk is likely due to the vaccines triggering a pre-existing asymptomatic condition, the researchers said. The study, which was published in the journal JAMA Neurology, was most concerned with the role that vaccines for hepatitis B and human papillomavirus play in the long-term risk for developing MS.   We also reported on a new iPad app that will allow clinicians and MS patients to track their disease course. The app, called Bioscreen, is currently in beta-testing at the University of California, San Francisco. The developers, including Pierre-Antoine Gourraud who is on MSDF’s scientific advisory board, assert that Bioscreen has the potential to be a powerful tool for researchers, clinicians, and patients. At the core of the app is a dataset of around 600 patients who have been participating in a data collection survey for the past 10 years. Physicians can compare their patient’s disease course with other confirmed MS cases and use that information to influence their recommendations. The researchers also believe that patients’ ability to visualize their own disease in this way will improve adherence to medical recommendations and ultimately strengthen the bond between patient and physician.   Every week we publish at least one “Research Roundup” where we curate stories from around the web related to multiple sclerosis. Recently we published roundups about advances in spinal cord injury treatment, the recipe for selling the perfect bogus drug, and the report of a rare brain infection in a patient taking dimethyl fumarate, trade name Tecfidera. To view Research Roundups, go to the “News Briefs” section of the “News and Future Directions” tab at msdiscovery.org. Look for the blue Research Roundup logo and stay up-to-date with all the latest MS news.   [transition music]   Now to the interview with Dr. Samuel Ludwin, a neuropathologist who is currently a visiting scientist at the Montreal Neurological Institute. Last week we aired an interview with Dr. Ludwin in which he discussed remyelination therapies. This week he speaks with MSDF about MS subtypes.   Interviewer – Dan Keller Welcome, Dr. Ludwin. Let’s talk about some of the subgroups of multiple sclerosis, as has been proposed by Professor Hans Lassmann, and you wrote an editorial some time ago about it. First of all, can you tell me what subgroups he identified and what progress there has been made since then?   Interviewee – Samuel Ludwin This is a very groundbreaking paper, very controversial, and over the years many people who have followed this particular pattern, others who’ve not been able to reproduce it and believe that the conclusions are not valid. However, what Claudia Lucchinetti and Hans Lassmann showed in a mammoth first-time examination of very acute lesions; they had access to a particularly unique group of specimens that are from both the Mayo Clinic and other areas, where very early lesions were examined. And in looking at this, they looked at patterns of tissue breakdown and the mechanisms of tissue breakdown, and essentially came up with four different categories. The two most important ones are very important to discuss because in the one, the features were very, very consistent with the kind of immune injury that one finds in experimental allergic encephalomyelitis where we know the damage has been caused by the injection of the antigen with a subsequent immune reaction to that antigen. And the other main group was one where there appeared to be a primary damage of some sort to the oligodendrocyte and then a subsequent immune reaction.   Now this is important for a couple of reasons, and the first is that there is a big debate going on in the multiple sclerosis literature or research as to whether the disease starts from the outside peripheral activation of immune cells and then homes in on the brain because they are cross-antigens or cross-antibodies or cross-cells, or whether the process actually starts with damage to something in the brain which subsequently sets off the – and this is called the “inside-out” or “outside-in” controversy at the same time. What this might mean, according to the way they have done the study – which was a very good one – was they suggested that there might be multiple mechanisms towards the end result of damage to oligodendrocytes and myelin, and subsequently the physical appearance of multiple sclerosis lesions.   Other people have challenged this and suggested that maybe it is a question of timing, and the mechanism is the same in all patients, but we’re looking at a different kind of progression and timing. And that controversy is still being discussed, as is the inside-out, outside-in phenomenon. But when you look at some of the things that might be causing these inside-out or their type 3 pattern where the primary damage could be in the oligodendrocyte, there are many reasons that the mechanism could be due to either stroke-like causes such as a lack of oxygen or blood flow that damages the oligodendrocyte, possibly certain infections that may target the oligodendrocyte. And we know that there are many mouse models where you can target oligodendrocytes with certain viruses. And those overlap very significantly with mechanisms of tissue damage in other diseases.   So it is a very important paper because it has set people thinking about multiple mechanisms. The fallout from this is that, in fact, when you have different mechanisms of causing disease, there are potentially different ways of treating it. And if you have a primary immune-based phenomenon from the outside, antiinflammatories as are given on disease-modifying therapies are perhaps the way to go, whereas if you’ve got something that is damaging it from the inside and some other cause, we need to elucidate what that cause is and go straight for that particular cause. In addition, what we are trying to find out is whether we can predict what sort of pattern has caused the disease, either with imaging or with biomarkers, and be able to do this without biopsies and other things so that patients can be treated accordingly. It’s an advance on perhaps what we might call personalized medicine in multiple sclerosis.    MSDF Are there imaging or clinical correlates of these different types of processes? You’re not going to do a biopsy on most people.   Dr. Ludwin No, there isn’t. But in fact, there are some therapeutic differences. For instance, in the type 2 pattern, which is the autoimmune pattern or the outside-in pattern, these patients respond very well to plasmapheresis where one is removing the offending gammaglobulin. And patients with the type 3, which is the main oligodendrocyte-based pattern of the disease, they don’t respond to that well. And that’s perhaps the best clinical differentiation that we know at the moment that helps us. A lot of the data is not clear. They based a lot of the data on the fact that they felt that every patient had a uniform pattern in the lesions. Other people have questioned this and found that there might be a multitude of different kind of patterns in the same patient, and therefore it supported modifications of the same inherent cause.   MSDF Does the efficacy of plasmapheresis correlate with the presence of oligoclonal bands in the CSF, or that’s not a correlation?   Dr. Ludwin There doesn’t seem to be a correlation, leastwise I know. Certainly plasmapheresis where we know that there is antibody, such as in neuromyelitis optica is more effective as a treatment early for diseases where we know that there is circulating antibody, but patients will have oligoclonal banding, I think, in both patterns.   MSDF You’d alluded to damage to the oligodendrocyte in one of these forms as the primary dysfunction or lesion. Does that imply that something is being exposed, an antigen that might be reacted to, or how is that leading to damage?   Dr. Ludwin Absolutely, that if you get damage to a tissue, various proteins are being broken down and antigenic epitopes are being exposed, which then are transported back to the peripheral lymphoid tissue for reactions to take place. I mean, there are counter-arguments to this. One can ask why, with a lot of trauma injury, a lot of stroke injury which is far more common than MS, why you don’t get a secondary immune response to that, even though we know many people with the genetic makeup makes them susceptible to MS or exist in the normal population, and almost certainly some of them have strokes. So there are questions on both sides and arguments. And we know from other experiments that you can induce circulating antigens with tissue destruction of any cause, and potentially these are circulating to be able to produce reactive antibodies in the periphery.   MSDF I think Lassmann showed that even in healthy people you can find CNS antigens in the cervical draining lymph nodes, which raises the same question you just brought up; why do some people have a reaction and some not?   Dr. Ludwin Absolutely, and there are now all sorts of theories coming out of the genetics that there are multiple genes, each having a small effect, but in totality may be adding up to a genetic defect that will allow some of these circulating cells to suddenly start having an effect.   MSDF Now it seems, in terms of thinking of personalized medicine, so much of it is empiric – what works works, and you try something else if it doesn’t. Is there a possibility of any harm from these treatments to people for whom it doesn’t work? Do you have to be very concerned about also first not do harm, especially considering you can’t tell the difference among these types from the start?   Dr. Ludwin Yeah, I think that it’s too early to apply personalized medicine to patients in this particular area in the different types. If you’re looking at personalized medicine that, you know, we treat patients as individuals, or we should, because a lot of the therapy is based on empiric choice and anecdotal experience sometimes with the clinician, and there’s no absolute algorithm that everybody uses to treat a patient. So in that sense, we already do practice it. But you’re quite right, a lot of that is anecdotal or empirical rather than mechanistic.   The do no harm is a very interesting point also, because you mustn’t forget that basically multiple sclerosis is an inflammatory disease, and very frequently we tend to look at inflammation as being something that’s bad. But the reason the body mounts an inflammatory infiltrate is usually to cure something or to clean up something that is attacking it from the outside. So in any kind of these interferences, we have to choose a very find balance between stopping an inflammatory infiltrate or reaction that may be doing a lot of good for the patient, while preventing it from its worst excesses.   And here, empiricism comes in quite well at the moment; we know which of these drugs that we give are more likely to give side effects, we know more about side effects than we do about potential for not allowing growth. We will stop a particular cytokine or block a particular protein in its action, but I think we should always be aware that the protein, if it’s a normal one and not abnormal protein, may be there for a reason and the patients will do worse if they don’t have this mess cleaned up, so to speak.   MSDF We’re also finding today that we’re almost living in a proinflammatory environment; it has repercussions in heart disease, dental disease, MS, fat is proinflammatory. So do all these things add to the risk in MS if there’s other inflammatory processes going on?   Dr. Ludwin Well, it’s not only the inflammatory processes that’s going on, it’s the things that are causing them. As you’re right, we are now discovering that things like salt, fast foods, the changes in the microbiota all tend to make us more proinflammatory. And certainly in experimental animals and now some human studies, it has been shown that experimental immune disease is worsened by a high salt intake which leads to increased salt in the tissues, as well as being prevented by some of these diseases. If you change the gut microbiota in many of these diseases from normal commensals into something that may be pathogenic, you will set off inflammatory autoimmune disease. It’s been shown very beautifully in ulcerative colitis and Crohn’s disease, and the same thing is now being looked at very strongly in multiple sclerosis, so certainly a proinflammatory environment.   On the other hand, it should be remembered that there’s certain kind of infections that produce a reaction that may very well be protective, and there’s some evidence that some of the parasites produce a factor and we believe it could be related to a particular type of protective T-cell that will then allow for patients to become resistant to multiple sclerosis. And there’s some very good data from South America that populations who’ve been exposed to parasites and have them are actually more resistant to multiple sclerosis, because the parasite has induced a protective antiinflammatory molecule in the cell as well. So it’s a very complex balance and we’re gradually discovering more and more about where this balance lies.   MSDF Might the prevalence of parasites account, at least in part, for the geographic distribution of MS?   Dr. Ludwin Well, parasites are just one part of it. There is a very strong feeling, and it comes back to also the gut microbiota – but it’s more than just gut microbiota; it’s environment microbiota – that this has a major role. And for many years, it wasn’t just parasites. People in the Third World had a much lower incidence of multiple sclerosis, and this could have been also from genetic reasons or from susceptibility. But it was not just for multiple sclerosis. All autoimmune disease was much lower in frequency in these populations, and the theory was that most of the people who grew up in developing countries were exposed to large numbers of bacteria and they developed robust immune systems, normal-functioning immune systems that could help them deal with it. And the theory is that in developed countries, the over-usage of antibiotics has aborted normal immune responses, and so in response to that autoantibodies are created and we are suffering the consequence of living too clean a life. And so I think if you look at that argument, it’s not just multiple sclerosis, it really has been mooted for the inflammatory bowel disease, juvenile diabetes, rheumatoid arthritis, and other immune diseases as well.   MSDF Thank you, this has been very good.   Dr. Ludwin Pleasure.   [transition music]   Thank you for listening to Episode Nineteen of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]

[intro music]   Host – Dan Keller Hello, and welcome to Episode Eleven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Jack Antel about remyelination and microglia. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Our latest data visualization reveals a mystery in relapsing-remitting MS. It appears that the annualized relapse rates of patients in the placebo arms of clinical trials – the placebo arms – have been decreasing since 1993. What could possibly account for this? We invite your hypotheses. Visit the MSDF website and go to our data visualizations page under “research resources.” From there you can connect to a discussion forum we’re hosting to share your opinions.   Deep brain stimulation is an extreme brain surgery that can lead to dramatic improvements in patients with Parkinson’s disease or obsessive-compulsive disorder. But in MS patients with tremor, the risk-benefit ratio varies a great deal from patient to patient. The surgery involves placing an electrode into the thalamus and stimulating the surrounding neurons to reduce tremor. However, no one is sure why the procedure works in some people with MS tremor and not in others. Last week, we published a news synthesis—including a dramatic video—on the efficacy of this surgery to treat the otherwise untreatable tremor in some MS patients.   We also reported on results from the phase 1 clinical trial of an anti-LINGO-1 remyelination agent. The drug, called BIIB033, is produced by Biogen Idec and proved safe and tolerable in healthy individuals and people with MS. In mouse models, the drug is shown to work by blocking LINGO-1. LINGO-1 prevents oligodendrocyte progenitor cells from differentiating into myelin-producing cells. The company is now conducting a phase 2 study to determine proper dosage in patients with MS.   [transition music]   Now to the interview. Dr. Jack Antel is a neurologist at the Montreal Neurological Institute and Hospital. His team studies remyelination and repair. He spoke with MSDF about how microglia and progenitor cells affect this process.   Interviewer – Dan Keller Welcome, Dr. Antel.   Interviewee – Jack Antel Thank you very much.   MSDF Where do things stand now? What is the thinking of remyelination? Is it a dynamic process? Is it something that happens all at once? Is there a balance between injury and repair?   Dr. Antel From the perspective of multiple sclerosis itself, we look to our pathologists who've examined the actual MS tissue, and they have established criteria by which they identify that remyelination has occurred, and thus this has been a major incentive to see whether one can accelerate that process. One can now somewhat question the certainty that we are distinguishing between actual remyelination and perhaps partial injury of myelin, and maybe part of what we've seen is actual injury rather than actual repair. The other side of the coin is from the experimental biologist who clearly have shown remyelination to occur and have identified progenitor cells as being the basis of remyelination in animal models. Now we have to bring the observation from the clinical pathology in humans together with those observations are we still certain that all of remyelination is dependent on new cells, or can previously myelinating cells still contribute. And in the context of the human disease, the issue is what is the total potential of the cells? Why doesn't everybody remyelinate? This is because there's intrinsic differences in the myelin cells that humans have. Could the myelin cells themselves be subject to injury? And also, the complicating feature is how much injury is there? So that, if the axons have been damaged, maybe they are not receptive to remyelination. And also, the chronic changes in the environment of all the other glial cells and their products in the human situation, which is after all a disease of months and years not of days and weeks, maybe this is an important influence as to why remyelination occurs or doesn't.   MSDF You had mentioned partial myelination or demyelination. When one looks at a path slide, is it possible to tell whether it's going up or down? Can you distinguish one from the other?   Dr. Antel So that active injury of myelin can be identified because in the active MS lesion myelin debris is freed up and picked up by the phagocytic cells – either the microglia or macrophages – so one can see that there is active injury. If one looks just at the myelin sheath itself, the criteria for remyelination is these sheaths have become rather thinned out, and the segment of the myelin sheath is shorter than in the naturally myelinated cell condition. The issue becomes whether are we absolutely sure that this is remyelination, or could one model developing this histologic feature in some way by injury? And I think that would be a very good challenge for the experimentalists to see if they can get an injury model that reproduces some myelin injury without actually killing the myelinating cells.   MSDF Besides being a target for the immune response, how do glia participate in the immune response?   Dr. Antel So the glia – we can refer both to the astrocytes and microglia – and as you mentioned one of the important issues I think with these cells is how they talk to the immune cells that are coming from the outside into the brain and modulating their properties. In addition, these glial cells themselves can influence the myelination process in several ways. One is that they can produce some of the same molecules that the immune cells produce or novel molecules that can either promote or directly inhibit the capacity of myelinating cells to function – so direct signaling effects on the myelinating cells. The other is they are producing molecules that change the environment so that processes either grow out or don't grow out from the myelinating cells. So we have to consider the glia, which are very dynamic and thus become a target for therapeutic manipulation, in terms of both their effects on immune cells but also can they be so, if you will, "good guys" or "bad guys" in terms of the promoting the myelination process.   MSDF We think of some of the present drugs as modulating the immune system and trafficking and its effect on effector cells. But do you think that some of these may be affecting bystander cells, or I suppose maybe they're not bystanders if they're actively involved. Could they have an affect on glia?   Dr. Antel I think that this is an emerging opportunity in the field because we are now having the first generation of drugs that actually access the central nervous system. The initial generation of drugs, many of the monoclonal antibodies, we felt were acting outside of the nervous system – either on immune cells themselves or on the cells that comprised the blood-brain barrier but with some particularly of the small molecule drugs that access the central nervus system – that these drugs have the capacity to interact with the neural cells. If we use as an example the family of agents that we refer to as this sphingosine-1-phosphate receptor modulators, S1P agents, there has long been data that these receptors are expressed on all cells, including all of the neural cells, and there is existing data that S1P modulators can affect the function of glial cells. Now how this translates into effects that are clinically relevant is the challenge that's ongoing now.   MSDF How does all of this relate to progressive MS?   Dr. Antel So progressive MS, I believe, is an entity that we have not totally understood yet, and we have to consider it in its parts, namely is progressive MS reflective of ongoing injury to the myelinating cells or the underlying axons? Is this a reflection of the injured cells no longer able to maintain themselves are they metabolically failing? And that can we distinguish these processes because if it's ongoing immune injury – whether related to the adaptive or innate immune system – then it makes sense to target those process. If it's an injury or metabolic failure, then that would be another approach. I think we have to consider whether progressive MS, again has evolved over many, many years, and whether one of our challenges is reducing the initial injury process can avoid many of these long-term events.   MSDF In secondary progressive MS, do you see that there's sort of a tipping point? Is there something different in secondary progressive once that occurs?   Dr. Antel It's difficult to provide an answer, and I think here is an area particularly where careful clinical studies are guiding us that the initial notion that multiple events triggered a later process would have been a very nice system to have because then stopping a process early would have predicted a beneficial later response. We are struck that the clinical data is suggesting that progression can occur perhaps even in the absence of ongoing inflammation whether the two are dissociated, at least in some cases, is a real concern. And thus, just controlling the initial immune response – because it triggers a later event – may not be sufficient. And the reverse, which I think has received perhaps less attention, is that from the clinical perspective multiple people have multiple disabling acute events and do not develop the progressive process. So it is not clear that the two are absolutely linked; whether there are genetic susceptibility factors that determine this have not yet emerged; whether it's the nature of the injury; or whether we have multiple diseases processes.   MSDF We often think of bench-to-bedside as the pathway for advancements. Now you had told me earlier that you're working with people in the opposite direction; you're finding things in the human condition and then leading to laboratory validation. Can you tell me a little bit about that?   Dr. Antel I think this is a very important aspect and why it is important that the clinical and clinical pathology experts really identify the core issues so that they can be taken to a laboratory and experimentally addressed. That in MS, we're dealing with a disease that develops over months and years making it more difficult to model it precisely. It's a disease where we have not established the initiating event. Whereas in the animal system, we usually use a arbitrary antigen if we were going to model an immune mediated disorder. We model the demyelination/remyelination process usually by acute toxins in the animal systems; whereas this is not the case in MS that specific exposure. And so I think we need to continue to develop our model systems that can induce some type of progressive disorder that is not specifically introduced perhaps by a specific antigen, at least the antigens we use currently.   MSDF Knowing that remyelination is possible, is there an implication that it may be going on in all of us in healthy brain at all times where you actually get turnover? And if so, can you capitalize on this kind of system?   Dr. Antel So the issue of turnover of myelin, I think, has not been emphasized sufficiently until recently both from the perspective if we have continuous turnover whether this may be one of the mechanisms whereby antigens are presented to the immune system. The other in terms of the turnover rate of myelin or oligodendrocytes – whether the health of these cells is damaged by the disease process, and whether a limiting factor over time is that the injury of the cells, which could be quite subtle – so that the cells are not killed, but they've impaired their function either to maintain the interaction with axons or the necessary transport of key molecules down the processes. Whether interruption of this then results in the inability of the cells to maintain their myelination properties and to continue the turnover or what might be a repair activity. And we interpret this as a later progression of the disease.   MSDF On the topics we've been discussing, is there anything important to add?   Dr. Antel I think the importance is that we now are turning our attention to these topics. That it is very timely that we do this – because until we could control the actual disease activity through immunomodulatory therapies – if that aspect was not controlled it would be much more difficult to think of trying to control the overall disease process. And also, as we couple the biology with careful clinical observations and the advances in imaging of the human brain, so that it gives us greater opportunities to bring our theories from the lab to the clinics and see whether we really impact in a positive way on the processes we've been discussing.   MSDF Very good. We appreciate it.   Dr. Antel My pleasure.   [transition music]   MSDF Thank you for listening to Episode Eleven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie [intro music]     Host – Dan Keller Hello, and welcome to Episode Eleven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Jack Antel about remyelination and microglia. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Our latest data visualization reveals a mystery in relapsing-remitting MS. It appears that the annualized relapse rates of patients in the placebo arms of clinical trials – the placebo arms – have been decreasing since 1993. What could possibly account for this? We invite your hypotheses. Visit the MSDF website and go to our data visualizations page under “research resources.” From there you can connect to a discussion forum we’re hosting to share your opinions.   Deep brain stimulation is an extreme brain surgery that can lead to dramatic improvements in patients with Parkinson’s disease or obsessive-compulsive disorder. But in MS patients with tremor, the risk-benefit ratio varies a great deal from patient to patient. The surgery involves placing an electrode into the thalamus and stimulating the surrounding neurons to reduce tremor. However, no one is sure why the procedure works in some people with MS tremor and not in others. Last week, we published a news synthesis—including a dramatic video—on the efficacy of this surgery to treat the otherwise untreatable tremor in some MS patients.   We also reported on results from the phase 1 clinical trial of an anti-LINGO-1 remyelination agent. The drug, called BIIB033, is produced by Biogen Idec and proved safe and tolerable in healthy individuals and people with MS. In mouse models, the drug is shown to work by blocking LINGO-1. LINGO-1 prevents oligodendrocyte progenitor cells from differentiating into myelin-producing cells. The company is now conducting a phase 2 study to determine proper dosage in patients with MS.   [transition music]   Now to the interview. Dr. Jack Antel is a neurologist at the Montreal Neurological Institute and Hospital. His team studies remyelination and repair. He spoke with MSDF about how microglia and progenitor cells affect this process.   Interviewer – Dan Keller Welcome, Dr. Antel.   Interviewee – Jack Antel Thank you very much.   MSDF Where do things stand now? What is the thinking of remyelination? Is it a dynamic process? Is it something that happens all at once? Is there a balance between injury and repair?   Dr. Antel From the perspective of multiple sclerosis itself, we look to our pathologists who've examined the actual MS tissue, and they have established criteria by which they identify that remyelination has occurred, and thus this has been a major incentive to see whether one can accelerate that process. One can now somewhat question the certainty that we are distinguishing between actual remyelination and perhaps partial injury of myelin, and maybe part of what we've seen is actual injury rather than actual repair. The other side of the coin is from the experimental biologist who clearly have shown remyelination to occur and have identified progenitor cells as being the basis of remyelination in animal models. Now we have to bring the observation from the clinical pathology in humans together with those observations are we still certain that all of remyelination is dependent on new cells, or can previously myelinating cells still contribute. And in the context of the human disease, the issue is what is the total potential of the cells? Why doesn't everybody remyelinate? This is because there's intrinsic differences in the myelin cells that humans have. Could the myelin cells themselves be subject to injury? And also, the complicating feature is how much injury is there? So that, if the axons have been damaged, maybe they are not receptive to remyelination. And also, the chronic changes in the environment of all the other glial cells and their products in the human situation, which is after all a disease of months and years not of days and weeks, maybe this is an important influence as to why remyelination occurs or doesn't.   MSDF You had mentioned partial myelination or demyelination. When one looks at a path slide, is it possible to tell whether it's going up or down? Can you distinguish one from the other?   Dr. Antel So that active injury of myelin can be identified because in the active MS lesion myelin debris is freed up and picked up by the phagocytic cells – either the microglia or macrophages – so one can see that there is active injury. If one looks just at the myelin sheath itself, the criteria for remyelination is these sheaths have become rather thinned out, and the segment of the myelin sheath is shorter than in the naturally myelinated cell condition. The issue becomes whether are we absolutely sure that this is remyelination, or could one model developing this histologic feature in some way by injury? And I think that would be a very good challenge for the experimentalists to see if they can get an injury model that reproduces some myelin injury without actually killing the myelinating cells.   MSDF Besides being a target for the immune response, how do glia participate in the immune response?   Dr. Antel So the glia – we can refer both to the astrocytes and microglia – and as you mentioned one of the important issues I think with these cells is how they talk to the immune cells that are coming from the outside into the brain and modulating their properties. In addition, these glial cells themselves can influence the myelination process in several ways. One is that they can produce some of the same molecules that the immune cells produce or novel molecules that can either promote or directly inhibit the capacity of myelinating cells to function – so direct signaling effects on the myelinating cells. The other is they are producing molecules that change the environment so that processes either grow out or don't grow out from the myelinating cells. So we have to consider the glia, which are very dynamic and thus become a target for therapeutic manipulation, in terms of both their effects on immune cells but also can they be so, if you will, "good guys" or "bad guys" in terms of the promoting the myelination process.   MSDF We think of some of the present drugs as modulating the immune system and trafficking and its effect on effector cells. But do you think that some of these may be affecting bystander cells, or I suppose maybe they're not bystanders if they're actively involved. Could they have an affect on glia?   Dr. Antel I think that this is an emerging opportunity in the field because we are now having the first generation of drugs that actually access the central nervous system. The initial generation of drugs, many of the monoclonal antibodies, we felt were acting outside of the nervous system – either on immune cells themselves or on the cells that comprised the blood-brain barrier but with some particularly of the small molecule drugs that access the central nervus system – that these drugs have the capacity to interact with the neural cells. If we use as an example the family of agents that we refer to as this sphingosine-1-phosphate receptor modulators, S1P agents, there has long been data that these receptors are expressed on all cells, including all of the neural cells, and there is existing data that S1P modulators can affect the function of glial cells. Now how this translates into effects that are clinically relevant is the challenge that's ongoing now.   MSDF How does all of this relate to progressive MS?   Dr. Antel So progressive MS, I believe, is an entity that we have not totally understood yet, and we have to consider it in its parts, namely is progressive MS reflective of ongoing injury to the myelinating cells or the underlying axons? Is this a reflection of the injured cells no longer able to maintain themselves are they metabolically failing? And that can we distinguish these processes because if it's ongoing immune injury – whether related to the adaptive or innate immune system – then it makes sense to target those process. If it's an injury or metabolic failure, then that would be another approach. I think we have to consider whether progressive MS, again has evolved over many, many years, and whether one of our challenges is reducing the initial injury process can avoid many of these long-term events.   MSDF In secondary progressive MS, do you see that there's sort of a tipping point? Is there something different in secondary progressive once that occurs?   Dr. Antel It's difficult to provide an answer, and I think here is an area particularly where careful clinical studies are guiding us that the initial notion that multiple events triggered a later process would have been a very nice system to have because then stopping a process early would have predicted a beneficial later response. We are struck that the clinical data is suggesting that progression can occur perhaps even in the absence of ongoing inflammation whether the two are dissociated, at least in some cases, is a real concern. And thus, just controlling the initial immune response – because it triggers a later event – may not be sufficient. And the reverse, which I think has received perhaps less attention, is that from the clinical perspective multiple people have multiple disabling acute events and do not develop the progressive process. So it is not clear that the two are absolutely linked; whether there are genetic susceptibility factors that determine this have not yet emerged; whether it's the nature of the injury; or whether we have multiple diseases processes.   MSDF We often think of bench-to-bedside as the pathway for advancements. Now you had told me earlier that you're working with people in the opposite direction; you're finding things in the human condition and then leading to laboratory validation. Can you tell me a little bit about that?   Dr. Antel I think this is a very important aspect and why it is important that the clinical and clinical pathology experts really identify the core issues so that they can be taken to a laboratory and experimentally addressed. That in MS, we're dealing with a disease that develops over months and years making it more difficult to model it precisely. It's a disease where we have not established the initiating event. Whereas in the animal system, we usually use a arbitrary antigen if we were going to model an immune mediated disorder. We model the demyelination/remyelination process usually by acute toxins in the animal systems; whereas this is not the case in MS that specific exposure. And so I think we need to continue to develop our model systems that can induce some type of progressive disorder that is not specifically introduced perhaps by a specific antigen, at least the antigens we use currently.   MSDF Knowing that remyelination is possible, is there an implication that it may be going on in all of us in healthy brain at all times where you actually get turnover? And if so, can you capitalize on this kind of system?   Dr. Antel So the issue of turnover of myelin, I think, has not been emphasized sufficiently until recently both from the perspective if we have continuous turnover whether this may be one of the mechanisms whereby antigens are presented to the immune system. The other in terms of the turnover rate of myelin or oligodendrocytes – whether the health of these cells is damaged by the disease process, and whether a limiting factor over time is that the injury of the cells, which could be quite subtle – so that the cells are not killed, but they've impaired their function either to maintain the interaction with axons or the necessary transport of key molecules down the processes. Whether interruption of this then results in the inability of the cells to maintain their myelination properties and to continue the turnover or what might be a repair activity. And we interpret this as a later progression of the disease.   MSDF On the topics we've been discussing, is there anything important to add?   Dr. Antel I think the importance is that we now are turning our attention to these topics. That it is very timely that we do this – because until we could control the actual disease activity through immunomodulatory therapies – if that aspect was not controlled it would be much more difficult to think of trying to control the overall disease process. And also, as we couple the biology with careful clinical observations and the advances in imaging of the human brain, so that it gives us greater opportunities to bring our theories from the lab to the clinics and see whether we really impact in a positive way on the processes we've been discussing.   MSDF Very good. We appreciate it.   Dr. Antel My pleasure.   [transition music]   MSDF Thank you for listening to Episode Eleven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]     Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]    

If Bigfoot walks through a forest and no one sees him, does he exist? It's the job of paranormal investigator Joe Nickell to find out! Discover whether eyewitness accounts are reliable when it comes to tracking down the hirsute big guy and other monsters. Also, on the subject of “seeing is believing”: how magic fools the brain. Plus, in our potpourri show: can music boost brain power? A new study says listening to music makes brains happy. Does this support the dubious “Mozart Effect,” that claims listening to Wolfie's compositions boosts IQ? And, skeptic Phil Plait on why the so-called “super moon theory” doesn't predict devastating earthquakes. It's Skeptic Check… but don't take our word for it. Guests: •  Joe Nickell – Paranormal investigator and author of Tracking the Man-beasts: Sasquatch, Vampires, Zombies, and More •  Stephen Macknik – Director of the Laboratory of Behavioral Neurophysiology at the Barrow Neurological Institute in Phoenix, Arizona •  Susana Martinez-Conde – Director of the Laboratory of Visual Neuroscience at the Barrow Neurological Institute in Phoenix, Arizona •  Phil Plait – Astronomer, and author of the Bad Astronomy blog at Discover Magazine •  Valorie Salimpoor – Researcher at Montreal Neurological Institute, McGill University, Quebec, Canada •  Penny Glass – Developmental psychologist and associate professor of pediatrics at the George Washington University School of Medicine Learn more about your ad choices. Visit megaphone.fm/adchoices

If Bigfoot walks through a forest and no one sees him, does he exist? It’s the job of paranormal investigator Joe Nickell to find out! Discover whether eyewitness accounts are reliable when it comes to tracking down the hirsute big guy and other monsters. Also, on the subject of “seeing is believing”: how magic fools the brain. Plus, in our potpourri show: can music boost brain power? A new study says listening to music makes brains happy. Does this support the dubious “Mozart Effect,” that claims listening to Wolfie’s compositions boosts IQ? And, skeptic Phil Plait on why the so-called “super moon theory” doesn’t predict devastating earthquakes. It’s Skeptic Check… but don’t take our word for it. Guests: •   Joe Nickell – Paranormal investigator and author of Tracking the Man-beasts: Sasquatch, Vampires, Zombies, and More •   Stephen Macknik – Director of the Laboratory of Behavioral Neurophysiology at the Barrow Neurological Institute in Phoenix, Arizona •   Susana Martinez-Conde – Director of the Laboratory of Visual Neuroscience at the Barrow Neurological Institute in Phoenix, Arizona •   Phil Plait – Astronomer, and author of the Bad Astronomy blog at Discover Magazine •   Valorie Salimpoor – Researcher at Montreal Neurological Institute, McGill University, Quebec, Canada •   Penny Glass – Developmental psychologist and associate professor of pediatrics at the George Washington University School of Medicine

Angela Genge is a professor of Neurology and Neurosurgery at McGill University, Medical Director of the Clinical Research Unit and Director of the ALS Clinic and Pain Clinic at the Montreal Neurological Institute and Hospital.