Brain Ponderings podcast with Mark Mattson

The facts that all human behaviors are controlled by the brain and that all crimes involve behaviors beg the question of if and how advances in neuroscience might improve the criminal justice system. Professor Stephen Morse at the University of Pennsylvania Law School and Center for Neuroscience and Society on problems of individual responsibility and agency. He is a pioneer on research at the interface of the law and neuroscience. In this episode Morse provides an historical perspective on NeuroLaw with examples of specific cases in which brain imaging data have been used as evidence as to a defendant’s mental state and responsibility. We also talk about psychopathy and drug addiction as predisposing factors in criminal behaviors and responsibility. Having been immersed in NeuroLaw for many decades, Morse concludes that substantive contributions of neuroscience to the law are very limited, but that this may change with future developments in the science.   LINKS: Professor Morse at Penn Law: https://www.law.upenn.edu/faculty/smorse/ Law and Neuroscience: report of the President’s Bioethics Commission: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033539/pdf/lsu012.pdf  NeuroLaw: Challenges and Limits: https://pdf.sciencedirectassets.com/276230/1-s2.0-C20190004591/1-s2.0-B9780128213759000037/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBwaCXVzLWVhc3QtMSJHMEUCIQDs%2F4PvoOovmb4J3nRy%2BIWJJm53ySCmeZ1m98ssPst45QIgf68T%2BYxRptjPz7G9wOXSA%2BgsesoxqkneG7dp4pZVtA8qswUIRRAFGgwwNTkwMDM1NDY4NjUiDGYAnlyiJhDC0fbDyiqQBUvl9RpbUHDEK7euZ3es2RO64UC3nA5dgPifofNG%2FA%2BxoTNlLLZo51v7RcON%2BWsZ0u7iASLCW08cEEABDRqOTrEpKYsbrf6PoMBXd9wYQbxs43YFjfZZa4VbkT594rQd9iR2%2B%2F4LHLRXi0hQVn4k2fGyQ%2Banl9L03kitshZpykjS8XAcEVPYRKWCZg6Jzpq6IMc2yAJ2kdNjKQbi%2BeBFSCVU3RQFkrBdpG7Bo1gFZfF8rL%2FLUwl0%2B2hb9N8jgzNzzni3WN7e3ughQcEh82%2Bg%2FaYT1FT83YIaYpnOjNIV%2BjgcKJWZ82D841CDSANw%2BPjLV6x7uZUqD9C2zhebrq0K4q8y4ylDGzamDM%2BqXgMHvp1vrB8%2FIWr4y17HN26XYw59MAXBNgCzbv0S45KRxvj%2FzTFTmf7h9RZbDfUVxJHoB3YtL4KsRzcuhT8UCsDcRW%2FosHx%2Bku8zfW3%2F4PvGsKbxWx%2BL7N1unXsjNZO8a5bCM4ABOMiJJMu6%2FYPfuqQ1TJn7hZLlHOqfmGineCO8UfSL%2BTu6n3gltTjBNJH0uOWZVi4Op6cU1Mmz223kWufye49wTyvWM8vHnvpidlL3h6Wrq1cxeycWFtBqHhrPrFbuOuykZdH12LEVCzTr6rDwVwPe8ZXQE%2Fp1t8hq6DqBBTqC%2BPfIUdlwRCKbeh6d0HGZJzvvVkd6AzfoZ8UkNZh1iBFvdmpPwSfRln6cIFD7RKnDTYaR8%2B8B5VxG0br75rKSYdn54zVE8PwtuPvq1uiseUcIwmJ%2BXhj2qZSXFP664Gi5dFsAK8MDUZD80TSKuj7EGvkXs9VbaL05OhDVnG9cl31JyNejWwKCKG%2BeFBPuIBD8kEHwGqxeFpojNqx1nlu8d1IvMPDX3qkGOrEB6XtS6d8NeOPl5NkCEZAOurR09k3ffY0%2BIjvh8lXHuXbrRL8mKfvFCxgR%2F81i%2F6c4VwWzRgloQVEOnjcwMpFtCkPCztkuqPcEfwas0Jl7Bwc3VapJTITwmXu2DY3rF6zHlz5sKWg50bWup7JCODKOc3FUKQD5vfYUk2RpkZP5uHsxbi0OBd7pIeeP2PCWjGbZ7vxB1GnPgy8V%2F0WmKPaeT0rtsef4vCzR5BlWB1yrMhGW&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20231024T125857Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTY2UJW5E5N%2F20231024%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=99ad1749a56b56597d9dbad545cd01d5715f58e79851a16c9558d80fe1ade2bf&hash=525472894c4bf63126822c9f34d8803fa325777ca4e8c7082ac033a0d30af25b&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=B9780128213759000037&tid=spdf-04e98b0c-1706-4bb3-b6b4-3a98d2aa235f&sid=aa84f1e132a57745745831c5ff1dcd2ff1c2gxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105b50045d58500107&rr=81b264ee3cc08c57&cc=us

Even as the carry out their usual functions molecular components of cells are damaged by oxygen free radicals and other processes. Cells remove such cellular trash by moving it into ‘acid baths’ called lysosomes in a process called autophagy. Research during the past 30 years has revealed the molecular mechanisms of autophagy and have provided evidence that impaired autophagy occurs in neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease.  In this episode professor David Rubinsztein provides an historical perspective on the discovery of autophagy and the current understanding of the molecular regulation of this fascinating process.  LINKS: Professor Rubinsztein’s lab page:  https://www.cimr.cam.ac.uk/staff/professor-david-rubinsztein-fmedsci-frs Review on autophagy: file:///Users/markmattson/Downloads/s41580-020-0241-0.pdf  Review on autophagy in neurodegenerative disorders: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930707/pdf/nihms-1771452.pdf

Expert in hormesis Edward Calabrese discusses the significance of hormesis in biology and medicine. They explore topics such as the beneficial effects of low-level stress, the co-evolution of plants and herbivores, hormesis and longevity, and the forces against healthy habits and prevention. They also touch on the positive effects of exercise on mood and well-being, personal nutrition and supplements, and the exploration of toxins in plants.

Inconspicuously tucked under the cerebral cortex at the back of the brain the cerebellum was long believed to only function as a controller of smooth and accurate body movements. During the past 40 years professor Rich Ivry at the University of California Berkeley has made major contributions to research that has revealed a much more complex repertoire of functions of the human cerebellum including roles in cognition, perception, and language. It turns out that there are at least as many neurons in the cerebellum as there are in the entire rest of the brain and that the cerebellum has strong connections to regions of the cerebral cortex involved in learning and memory and decision-making. In this episode professor Ivry talks about how different experimental approaches and modern technologies have been used to elucidate the functional organization of cerebellar circuits and the consequences of cerebellar dysfunction. LINKS: The Ivry Laboratory at Berkeley:  http://ivrylab.berkeley.edu/rich-ivry.html Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514106/pdf/nihms-1679908.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686189/pdf/nihms-1530513.pdf   Examples of studies of patients with damage to the cerebellum: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10200308/pdf/awac072.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245126/pdf/elife-66743.pdf

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/