Brain Ponderings podcast with Dr. Mark Mattson

David Nutt has made major contributions to understanding mechanisms by which psychoactive drugs affect the brain and has conducted numerous clinical trials of a wide range of drugs in patients with various mental disorders. He has also been an outspoken critic of the disconnect between drug science and government drug policies. For example, alcohol is legal, widely available, and causes tremendous harm to individuals and society. On the other hand psychedelics are illegal and yet very safe and can be very beneficial for mental health. In this episode I talk with Professor Nutt about the relative harms and benefits of different drugs to individuals and society. His efforts and those of many other scientists and psychiatrists are pushing governments to accept the facts and help facilitate rather than obstruct science-based progress in drug research and use of that knowledge for medicine and society. David Nutt is a distinguished professor in the Division of Brain Sciences at Imperial College in London. He is the founder and chairman of Drug Science and host of the Drug Science Podcast. LINKS: Drug Science website: https://www.drugscience.org.uk/drug-information/?gad_source=1&gclid=CjwKCAjwuJ2xBhA3EiwAMVjkVG_peCbmMCI9tKIYTUldYjmfjHNxCLeLX2WYvkLPezA7zaJpciU8HhoCGHcQAvD_BwE Drug Science podcast: https://open.spotify.com/show/2hLSRIS777SKphWxv4HyDK Recent relevant articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291338/pdf/fpsyt-14-1183740.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669276/pdf/fpsyt-13-1027159.pdf https://www.sciencedirect.com/science/article/pii/S0028390822003161?via%3Dihub https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625009/pdf/nutrients-13-03938.pdf

Some elderly individuals remain cognitively 'sharp as a tack' despite the accumulation of large amounts of amyloid in their brains, whereas others exhibit profound cognitive impairment with less amyloid pathology. In this episode Columbia University Professor Yaakov Stern talks about the concepts of 'cognitive reserve' and 'brain maintenance' and how he and others have elucidated factors that explain individual differences in cognitive trajectories during aging. The data show that regular exercise and intellectually challenging endeavors promote successful brain aging in the absence or presence of Alzheimer's disease pathology. We also discuss neural mechanisms that may explain cognitive reserve and brain maintenance during aging. LINKS: Professor Stern's webpage at Columbia University: https://www.neurology.columbia.edu/profile/yaakov-stern-phd Review articles on cognitive reserve and brain maintenance: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507991/pdf/nihms416640.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517622/pdf/acab049.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859943/pdf/nihms-1530897.pdf

What are the foundational principles by which acquired information is organized and processed in the human brain? In this episode University of Rome Professor Anna Borghi talks about several prominent working theories of cognition including embodied cognition (interactions with objects and other people), inner speech, and abstract concepts. She talks about how language is a prominent feature of these theories and the methods used to test these theories. We also touch on evolutionary and developmental perspectives that help explain these cognitive abilities. LINKS The embodied mind extended: using words as social tools: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640182/pdf/fpsyg-04-00214.pdf Inner speech: https://www.cell.com/action/showPdf?pii=S1364-6613%2823%2900210-3 Abstract concepts: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674746/pdf/426_2022_Article_1698.pdf

Traumatic brain injuries (TBI) are a major cause of long-term disability and burden on families and health care systems. University of Cambridge Professor David Menon is a leader in global efforts to better understand and treat TBI. In this episode Dr. Menon talks about what happens to neurons, glial cells, and blood vessels in the brain after a TBI. He explains risk factors for TBI, how patients with TBI are currently evaluated and treated, and emerging therapeutic interventions to enhance their recovery. LINKS Review articles on TBI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427240/pdf/nihms-1921257.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253145/pdf/12028_2020_Article_994.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809021/?report=printable

Mitochondria are best known as the powerplants within cells. But recent research is revealing that mitochondria play fundamental roles in regulating the structure and function of neuronal networks and the behaviors that those networks control. Martin Picard directs the Mitochondrial Psychobiology Group at Columbia University. In this episode I talk with Dr. Picard about: the biogenesis and movement of mitochondria within cells, the disposal of damaged mitochondria, the diversity of mitochondria within and amongst neurons in the brain, how this diversity contributes to neuroplasticity, and how aberrancies in mitochondria are involved in mental and neurodegenerative disorders. We also talk about how 'bad' and 'good' stress affect mitochondria. LINKS: Reviews on Mitochondrial Diversity and Psychobiology: file:///Users/markmattson/Downloads/s42255-023-00783-1%20(1).pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692202/pdf/nihms-1844878.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339630/pdf/nihms-1529320.pdf Mitochondrial Diversity and Anxiety: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415311/pdf/41467_2023_Article_39941.pdf Human Brain Map of Mitochondrial Diversity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942385/pdf/nihpp-2024.03.05.583623v1.pdf

In a fascinating discussion, Charles Nemeroff, a renowned psychiatrist and neuroscientist at UT Austin, sheds light on the alarming rise of depression, particularly among youth. He connects early life adversity and social media to increased risk. The conversation delves into neurobiology, the intricacies of treatment responses, and how modern interventions can better target depression. Nemeroff also explores the potential of psychedelics, emphasizing their promise and ethical considerations, while addressing pressing issues like access to care and resilience in the face of trauma.

Historically, microglia were viewed only as the brain's immune cells that respond to brain injury or infections. While this is true, recent research has shown that microglia play important roles in responding to and regulating neuronal network activity, and adaptations of the brain to physiological challenges such as exercise and intellectual challenges. Microglia are increasingly recognized for their roles in neuroplasticity including learning and memory and regulation of emotions. Professor Long-Jun Wu is working at the forefront of research on microglia and their roles in normal brain function and in disorders such as chronic pain and Alzheimer's disease. In this episode I talk with Dr. Wu about his research and its implications for brain health and new therapeutic approaches for neurological disorders. LINKS: Review articles: https://www-sciencedirect-com.proxy1.library.jhu.edu/science/article/pii/S0166223623002904 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113084/pdf/nihms-1663302.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599472/pdf/nihms-1529800.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043090/pdf/12264_2022_Article_937.pdf

Transcranial magnetic stimulation (TMS) is a non-invasive technology that enables stimulation (or inhibition) of specified neuronal networks in the brain. In this episode Alvaro Pascual-Leone, a Professor in Neurology at Harvard Medical School, talks about the principle and practice of TMS and its use for the treatment of a range of brain disorders including depression, stroke, and cognitive impairment, chronic pain, and traumatic brain injuries. The technology has advanced to a point where portable in-home devices can be used for treatments under the supervision of medical experts. TMS is also being used to understand how neural networks respond to injury and disease. TMS promises to be a valuable addition to therapies for mental and neurodegenerative disorders. In addition to TMS Dr. Pascual-Leone is working to develop and apply artificial intelligence and digital technologies and intelligent therapy assistant approaches to the broader health care system. In addition to being a Professor at Harvard, Dr. Pascual-Leone is Medical Director, Deanna and Sidney Wolk Center for Memory Health; Senior Scientist, Hinda and Arthur Marcus Institute for Aging ResearchvHebrew SeniorLife; Co Founder and Chief Medical Office Linus Health; Co Founder TI Solutions LINKS: Review articles on TMS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700722/pdf/41386_2022_Article_1453.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996329/pdf/nihms-1787298.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863979/pdf/CPJ2012000737.pdf Article on digital technology intelligent therapy assistants: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639502/pdf/fdgth-03-755008.pdf

In 1997 Makoto Kuro-o and his colleagues reported that they had accidentally discovered a gene that encodes a protein that slows aging and extends the lifespan of mice. They named the protein 'Klotho' after the Greek goddess that 'spins the thread of life'. During the past decade University of California San Francisco professor Dena Dubal has shown that Klotho can enhance learning and memory and protect neurons and synapses aging dysfunction and degeneration in mouse models of Alzheimer's disease. Klotho production is increased by exercise and intermittent fasting. In this episode Dr. Dubal talks about her research on Klotho and the potential of Klotho as a treatment for cognitive impairment, Alzheimer's disease, and other brain disorders.. LINKS: Review article on Klotho: file:///Users/markmattson/Downloads/s41581-018-0078-3%20(1).pdf Klotho enhances cognition in old nonhuman primates: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432271/pdf/43587_2023_Article_441.pdf Klotho treatment in a mouse model of Alzheimer's disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323521/pdf/zns2358.pdf Klotho treatment in a mouse model of Parkinson's disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816951/pdf/nihms941402.pdf Intermittent fasting and Klotho: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760057/pdf/41380_2021_Article_1102.pdf Neuronal activity and Klotho: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681535/pdf/10.1177_0271678X18762700.pdf

The brains of males and females are different and it is important to understand how these differences give rise to different behavioral traits of men an women. These sex differences arise during brain development, manifest throughout life and are controlled in part by estrogen and testosterone. The brains of females and males, and their differential vulnerability to mental and other neurological disorders may be influenced by prenatal and early life environmental factors including stress or exposure to pollutants such as 'forever chemicals'. Professor Mariha Kundakovic at Fordham University is making major contributions to understanding brain sex differences and particularly the roles of 'epigenetic' molecular and structural modifications to the genome. Here she talks about her research and its implications for the causes of and treatments for anxiety disorders and depression. LINKS: Review article: epigenetic mechanisms and sex differences in the brain and behavior: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841872/pdf/nihms-1935382.pdf Review on influence of hormones on the brain during the estrous cycle: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050126/pdf/nihms-1850437.pdf Sex hormones and risk for anxiety disorders and depression: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715398/pdf/nihms-1848030.pdf