Brain Ponderings podcast with Dr. Mark Mattson

Chronic pain affects more than 20 percent of people and is the leading cause of disability and loss of productivity. Recent development in technologies and protocols for electrical non-invasive or invasive stimulation or inhibition of specific pathways in the brain or spinal cord are being developed. At the forefront of this area of neurology is Dirk de Ridder, Professor of Neurosurgery at Otago University and co-founder of the BRAI3N Center for Neuromodulation in Ghent Belgium. In this episode he describes the triple network model of brain circuitry for pain: a lateral painfulness pathway from the spinal cord to the brain; a medial pathway in the brain that mediates suffering; and an inhibitory pathway for pain suppression. He talks about how EEG recordings can be used to determine which pathways are altered in patients with chronic pain and therefore which location and protocol for stimulation is most likely to be effective. Rapid progress in the development of these technologies is resulting in much needed help for those who suffer from and are disabled by chronic pain. LINKS BRAI3N Center (Advanced, International, Innovative and interdisciplinary neuromodulation https://www.brai3n.com/en/ Triple Network Model of Chronic Pain https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934778/pdf/fneur-13-757241.pdf Burst stimulation for chronic pain https://www.brainstimjrnl.com/action/showPdf?pii=S1935-861X%2823%2901872-7 Chronic pain is a brain imbalance https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966784/pdf/fcab014.pdf

The discomforting feeling of hunger evolved to motivate searching for food and is therefore critical for survival. However, for modern-day humans living in environments where food is continuously available excessive hunger can result in obesity. In this episode Yale University professor Tamas Horvath talks about 'hunger neurons' in the hypothalamus and how they are regulated by glucose, fatty acids, and signals coming from the gut. He also discusses interesting roles for mitochondria in the hunger neurons in their sensing of metabolic states. His research is also providing important insight into alterations in neural circuits that occur in anorexia nervosa. Links: Professor Horvath's Lab page: https://medicine.yale.edu/lab/horvath/ Review articles: https://www.cell.com/action/showPdf?pii=S1550-4131%2815%2900483-0 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634671/pdf/nihms729589.pdf Anorexia mouse model: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415190/pdf/BioProtoc-13-15-4730.pdf

In this episode of Brain Ponderings I talk with the German neuroscientist Wolf Singer about the hard problem of consciousness and how it might be solved. Wolf is a Professor at the Max Planck Institute of Brain Research and the Institute for Advanced Studies in Frankfurt Germany. Perhaps more than anyone else in the world Wolf has elucidated how neuronal networks in the cerebral cortex process information. His research has provided evidence that - unlike modern machine learning and deep learning artificial intelligence systems - the human brain functions as an analog computer wherein computations are performed in the high dimensional dynamic state space provided by the non-linear dynamics that evolve in the recurrent network of delay coupled oscillatory circuits." LINKS: Wolf's Lab Page: https://brain.mpg.de/singer Perspective on the Hard Problem of consciousness: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824320/pdf/fnsys-13-00058.pdf Recurrent dynamics in the cerebral cortex: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379985/pdf/pnas.202101043.pdf Nature Communications 2023. Encoding by neuronal response sequences: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212951/pdf/41467_2023_Article_38587.pdf

The human brain is often depicted as billions of nerve cells connected to each other in circuits through which electrical impulses flow. But this vision of the brain ignores the fact that in addition to nerve cells the brain also houses as many or more other cells called glia which surround and are intimately associated with the nerve cells. There are three types of glia – astrocytes, oligodendrocytes, and microglia. The research of Alex Verkhratsky has revealed critical roles for glial cells in supporting the survival and functions of neurons, and modulating neuronal network activities. Here he talks about these roles for glial cells with emphasis on calcium and ATP as signals within and between astrocytes and neurons. He also talks about how alterations in glial cells contribute to neurodegenerative disorders such as Alzheimer's disease. LINKS Alex's Wiki page: https://en.wikipedia.org/wiki/Alexei_Verkhratsky Review articles https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788756/pdf/zqaa016.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266005/pdf/nihms-1581159.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188604/pdf/nihms-1581152.pdf Evolutionary perspective on calcium and ATP as universal cellular signals https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938020/pdf/rstb20150419.pdf

Mark Tuszynski, a neurologist and neuroscientist from the University of California San Diego, discusses his research program on reversing neurological deficits in spinal cord injury and Alzheimer's disease. He explores the use of neurotrophic factors and stem cells in repairing damaged circuits and restoring function in rat and monkey models. Tuszynski also talks about clinical trials and the potential of regenerative medicine technologies.

Professor Alan Evans at McGill University in Montreal is a leader in the global effort to use computing power and artificial intelligence to analyze and interpret the massive amounts of brain structural and functional imaging, clinical, behavioral, and molecular data amassed by neuroscientists, radiologists, and neurologists. The creation of international consortia, procedures for data registration, quality control methods, and analysis algorithms have enabled large open science databases that are being mined by scientists throughout the world. These efforts have resulted an explosion of new knowledge of the human brain – its development and function throughout life, as well as what goes wrong in various disorders. In this episode Professor Evans talks about some of the major big data projects and how they are facilitating new discoveries about the human brain. LINKS: McGill Centre for Integrative Neuroscience; LORIS, CBrain, imaging software: https://mcin.ca/technology/visualization/atelier3d/ Cyber infrastructure at the Montreal Neurological Institute: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216036/pdf/fninf-10-00053.pdf BigBrain: https://bigbrainproject.org/ BigBrain 3D Atlas article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159250/pdf/pbio.3000678.pdf Canadian Open Science Platform: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374086/pdf/pcbi.1011230.pdf Brain network architecture in autism: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005951/

University of Cambridge Professor Trevor Robbins is a highly cited neuroscientist who has made major contributions to understanding how neuronal circuits and neurotransmitters control behaviors in health and brain disorders. In this episode I talk with Trevor about obsessive-compulsive disorder (OCD) an often debilitating mental disorder in which the affected person exhibits repetitive behaviors that interfere with their lives. He talks about studies in humans and animal models that point to problems in the communication of the frontal lobes (which function in cognitive control and decision-making) with the basal ganglia (which mediates habitual / automatic body movements). We also talk about treatments for OCD which involve drugs that increase serotonin levels at synapses and, in severe OCD cases, deep brain stimulation or surgical excision of the cingulate cortex. LINKS Trevor Robbins webpage: https://www.neuroscience.cam.ac.uk/directory/profile.php?Trevor Trevor Robbins publications on PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=robbins+tw&sort=date&size=200 Review article on OCD: https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930073-X Review article on cognitive control and executive function tests: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617292/pdf/41386_2021_Article_1132.pdf Recent article on delayed development of PFC and mental disorders: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202801/pdf/41591_2023_Article_2317.pdf

University of Cambridge Professor Trevor Robbins is a highly cited neuroscientist who has made major contributions to understanding how neuronal circuits and neurotransmitters control behaviors in health and brain disorders. In this episode I talk with Trevor about obsessive-compulsive disorder (OCD) an often debilitating mental disorder in which the affected person exhibits repetitive behaviors that interfere with their lives. He talks about studies in humans and animal models that point to problems in the communication of the frontal lobes (which function in cognitive control and decision-making) with the basal ganglia (which mediates habitual / automatic body movements). We also talk about treatments for OCD which involve drugs that increase serotonin levels at synapses and, in severe OCD cases, deep brain stimulation or surgical excision of the cingulate cortex. LINKS Trevor Robbins webpage: https://www.neuroscience.cam.ac.uk/directory/profile.php?Trevor Trevor Robbins publications on PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=robbins+tw&sort=date&size=200 Review article on OCD: https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930073-X Review article on cognitive control and executive function tests: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617292/pdf/41386_2021_Article_1132.pdf Recent article on delayed development of PFC and mental disorders: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202801/pdf/41591_2023_Article_2317.pdf

Imagine a world in which everyone got along and cared for the well-being of everyone else. In this episode I talk with Professor Rob Malenka of Stanford University about the neural circuits and neurochemicals involved in prosocial behaviors and empathy. Malenka's laboratory has used cutting-edge technologies to identify the brain regions and specific synapses that mediate prosocial behaviors and how MDMA enhances these behaviors. He also talks about fascinating experiments which showed that neurons in a brain region called the anterior cingulate cortex mediate empathy-like behaviors in mice. Malenka's research is leading to new insights into how we interact with other people and how these interactions can be more rewarding and productive. We also talk about the neurobiology of addiction including the recent epidemic of food addiction and obesity. LINKS Professor Malenka's Stanford profile: https://med.stanford.edu/profiles/robert-malenka Review article on the neurobiology of prosocial behavior: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169714/pdf/nihms-1648144.pdf Oxytocin and reward: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214365/pdf/nihms-989254.pdf Prosocial and rewarding properties of MDMA: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123941/pdf/nihms-1565640.pdf Social transfer of pain and analgesia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952019/pdf/nihms-1672720.pdf Food addiction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035198/pdf/41467_2021_Article_22430.pdf

Every year humans consume approximately 10 million tons of crustaceans – crabs, lobsters, shrimp, and crayfish. In order to grow these creatures must shed their hard exoskeleton in a remarkable process called molting. Molting is controlled by a neuropeptide which is released into the blood and acts to suppress the production of a steroid molting hormone produced in the Y organ. In this episode Professor Don Mykles of Colorado State University talks about the remarkable process of molting and the cellular and molecular processes that control the production of the molting hormone and its actions on tissues in the body. Mykles' laboratory discovered that the mTOR signaling pathway is of fundamental importance in the control of molting. This of considerable interest because mTOR is believed to play pivotal roles in neuroplasticity, aging, and developmental brain disorders in humans. LINKS: CSU Crab Lab webpage: https://mykleslab.biology.colostate.edu/researchers_mykles.html Review article on the neuroendocrine control of molting: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256442/pdf/fendo-12-674711.pdf The 'CrusTome': https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320764/pdf/jkad098.pdf