Brain Ponderings podcast with Mark Mattson

In this episode I provide an overview of the evidence that certain chemicals produced by plants and fungi are beneficial for brain function and health. I focus on the fact that the function of these phytochemicals or mycochemicals in the plants or mushrooms is to defend them from being consumed by insects and other animals.  We and other animals evolved mechanisms to tolerate the noxious chemicals.  We avoid too much of them because they have a bitter taste, and our cells respond to the chemicals by activating adaptive stress responses (antioxidant enzymes, protein chaperones, neurotrophic factors, etc). By these hormesis-based mechanism way plant-based diets enhance brain resilience and counteract aging and disease processes. LINKS Articles on dietary phytochemicals and brain health https://pmc.ncbi.nlm.nih.gov/articles/PMC4081729/pdf/pr.113.007757.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC5841445/pdf/nihms946635.pdf https://www-sciencedirect-com.proxy1.library.jhu.edu/science/article/pii/S0166223606002001 Review article on mycochemicals https://pmc.ncbi.nlm.nih.gov/articles/PMC10647524/pdf/ijms-24-15596.pdf Evolutionary perspectives https://pmc.ncbi.nlm.nih.gov/articles/PMC4586293/pdf/nihms678801.pdf https://www.sciencedirect.com/science/article/abs/pii/S1087184523000439?via%3Dihub Recent Nature Medicine study https://www.nature.com/articles/s41591-025-03570-5

The vast majority of research on the cellular and molecular mechanisms of the storage and retrieval of memories has focused on the excitatory glutamatergic neurons that convey signals into and throughout the brain. However, recent research has revealed the importance of widespread oscillations in neural network activity (particularly gamma and theta frequencies) in cognition. In this episode Professor Dietmar Schmitz talks about features of short- and long-range neural connectivity and their roles in cognition with a focus on inhibitory GABAergic interneurons. Different subtypes of GABAergic neurons have different molecular signatures, shapes, electrophysiological properties, and connectivity patterns. These different GABAergic neurons serve specific functions in memory, and information processing. LINKS: Schmitz lab page: https://schmitz.neurocure.de/ GABAergic interneurons and memory: https://www.cell.com/action/showPdf?pii=S0896-6273%2823%2900475-0 microcircuits and spatial coding: https://journals.physiology.org/doi/epdf/10.1152/physrev.00042.2020 hippocampal CA3 module: https://pmc.ncbi.nlm.nih.gov/articles/PMC10861929/pdf/pnas.202312281.pdf  

Research has shown that excessive dietary protein intake and high amounts of branch-chain amino acids (BCAA) in particular can accelerate aging and exacerbate chronic diseases of aging. In this episode University of Wisconsin Assoc. Professor Dudley Lamming talks about the cellular amino acid sensing mTOR pathway and its influences on aging and disease processes. The Lamming laboratory is making major contributions to establishing how amino acid intake affects cells and organ systems in health and disease. This research has important implications for optimizing health throughout the lifespan.   LINKS Lamming lab webpage:  https://lamminglab.medicine.wisc.edu/ Review article: https://pmc.ncbi.nlm.nih.gov/articles/PMC9197406/pdf/ACEL-21-e13626.pdf Protein restriction in Alzheimer’s mouse model: https://pmc.ncbi.nlm.nih.gov/articles/PMC11189507/pdf/41467_2024_Article_49589.pdf BCAA restriction, aging, and lifespan: https://pmc.ncbi.nlm.nih.gov/articles/PMC10655617/pdf/nihms-1939504.pdf

Dopamine is best known as a neurotransmitter involved in the experiencing of pleasure and reward, and for its role in addiction to drugs, gambling, food, etc.  But dopamine is also very important in the brain’s ability to evaluate computational tradeoffs (cost versus benefit) and make decisions.  In this episode Roshan Cools a Professor of cognitive neuropsychiatry at Radbout University in the Netherlands talks about how dopamine normally controls the neuronal circuits in the striatum and prefrontal cortex that regulate motivation and cognitive control. By combining PET imaging to measure relative dopamine release with various cognitive control tasks and administration of drugs such as methylphenidate (Ritilin) that affect dopamine signaling  she found that every individual has their own dopamine ‘set point’. She talks about how dopaminergic drugs enhance cognitive control in ADHD patients but impair cognitive control in patients with Parkinson’s disease.  We also talk about potential pharmacological and behavioral modifications to optimize cognitive control in healthy people.  LINKS Professor Cools web page: https://www.roshancools.com/ Chemistry of the adaptive mind: https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930838-4 Dopamine’s role in making cost versus benefit decisions: https://pmc.ncbi.nlm.nih.gov/articles/PMC8282630/pdf/nihms-1697802.pdf

In this episode I talk with Professor Maryanne Garry at the University of Waikato New Zealand about several interrelated realms of human cognition that are fundamental to changes in the behaviors of individuals and social groups as influenced by electronic media and artificial intelligence.  Dr. Garry has devoted her career to understanding how memories of one’s past experiences can be distorted, how false information can become engrained in one’s system of beliefs. She talks about individual and collective memories, and the brain’s source monitoring systems and how they are influenced by group identity, repetition of information (whether true or not). Interestingly although memories of untruths can be retracted when new information is provided they can still influence one’s decision-making.  She also talks about how social media and AI (LLMs) influence the brain’s source monitoring systems and potential approaches to ameliorating their adverse effects on mental health and societal discord. LINKS Dr. Garry’s lab webpage: https://www.garrylab.com/ Collective and autobiographical memories: https://www-tandfonline-com.proxy1.library.jhu.edu/doi/epdf/10.1080/09658211.2022.2154804 Retracted memories: https://pmc.ncbi.nlm.nih.gov/articles/PMC9365748/pdf/13421_2022_Article_1328.pdf LLMs and the institutionalization of misinformation: https://pdf.sciencedirectassets.com/271877/1-s2.0-S1364661323X00138/1-s2.0-S1364661324002213/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEG4aCXVzLWVhc3QtMSJGMEQCIA9kHgyXdZwhJDF2Nc6gQiDwWhuj%2F9fvysEcbyMKnaM8AiBEX6%2BAkbxOT%2FT%2FJCTkVCeOnibe%2Fin%2BeiHRN8auAjLO7yq8BQin%2F%2F%2F%2F%2F%2F%2F%2F%2F%2F8BEAUaDDA1OTAwMzU0Njg2NSIMnDX%2Bz%2BiS%2BD9b8%2BsCKpAFlPWcxi2Nu4wg%2FlKU8mSVoZQPyiR6LQkJokbH6TlJvixjI04Sd92Kj5SSAHB8QvzpkbIuJoErUOjgSlkpGTlKK7kMqkMt2S%2FSmUyp5OzH5PlhGyxSi3Lpq%2Bdjol9vmiF9rXTEeHeRrHzUh48X4HajvARh9q6lC6v%2FCSx84dpolcD3kMlhYIEuYfJbVc%2Fm4k%2F9xtjX2NtA3BhLHFs8nzUuuDcNtLxZ3mi7SLbQz9oBGMdeJFd2bBjf%2ByCpjqUl%2Bs9ALlI75kYC1aDPdB2f84XWB78f9CKz%2FtNob%2FjKE9tMcwB3Dni8%2FtndhQRjybd74siNn2sApJu%2FXKwgKsqJEvKP8CDYYTgnSVrRAseqXSdLKoA63G91ZG9K7nOjODivQI%2BpzciLPlvzYVjpeEJ5LE3PC5VVYxCkOQKUtwDvUgXigGtfHsgazln3m8WMBxakhHXrKEWK7q%2FuxuLBle%2BD%2BK%2FdM1aw2JpS7hyllAgfZ4cuSBexwzQ%2B3OjGg4Fe2MBdTmpa0ZG9WT7B7KNo2FxoiKEZJupQ3z%2FaMOIBCMCqa0EvuMCQpIqZKS8zxngNpJeOVpTuWv%2BJ3EQjM3T6GL9hxNA%2BszUz7MR7KN6so2RZvU32fCtHB14j2vHVXkaytDu653flfPWASPWQKprXowbOsghYz0UegMyUjO1a67axaYcTUrVAt7OxvM%2BwyZDkSPJhOWHDfcSyL30v%2BhTLjWxGRy4GdrEndVdgAw3RmjDWx0E4CrmUkycwWQND01xhJI6IijMO%2BgoJ%2FFVSnrNNvGVGCCtU80%2FylVKonMGKTDptdPrqsi8aQDdQYdyL5sq4itFXa6Obi0EvBTjlB8p%2BMORusgVwSP9PBJFbLLbT%2FnxegI2FJJ0wh5%2BMvgY6sgFhGU%2FH5TGFnQMV5o1J5r37XL5V8jHthF%2FO3kUtL%2Fk6oDRUfFYPQxvyRxi0EzFaGcDu7jYC53O%2BZxrzPgPJS1qP6%2BNJu6%2FDls8iyGvg3JAi85RLRRgZlhp3wnfLghXW4W6VnmXzQzMUdjCahckzzB9w8XVmhGrXw%2F4JIvHgSx73D6oVy%2BPMi4h%2F4I5T08ApqPSaR7bkrnYvAtWgfjRynIpiabV%2BBisHSuNwL11EsBTf3auq&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250301T144026Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTY4USPLILK%2F20250301%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=03ec372fac008431242909cb94e0acfca84a8a7d4fdc142df102bf78149b9761&hash=1da48c96274cce2ef2914eaf9bd37a118e05e359da92f349fb5c1a767dcd852e&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S1364661324002213&tid=spdf-52d87662-932c-46b0-925b-296bc39e2460&sid=f0d8a6a836dc5742e59bb5900fc7ac98a3f4gxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&rh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105a505f56585c0053&rr=919968d1f9843b0b&cc=us

It had long been thought that the brain was ‘immunologically privileged’ (physically separated from the immune system).  However, this dogma was overturned by a series of discoveries including those made by Professor Michal Schwartz at the Weizmann Institute. In this episode I talk with Michal about the different types of immune cells that are located in ‘immunological niches’ of the brain (choroid plexus, perivascular space, meninges..) and how these cells play critical roles in maintaining normal brain health and function (neurogenesis, synaptic plasticity, learning and memory). In addition, Michal tells us how the immune system is vital for healing and protecting the brain in case of injury or disease in a process called protective autoimmunity. LINKS The Schwartz laboratory webpage: https://www.weizmann.ac.il/brain-sciences/labs/schwartz/ Review article in Science: https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.abo7649 Review article in Neuron: https://pdf.sciencedirectassets.com/272195/1-s2.0-S0896627324X00021/1-s2.0-S0896627324008821/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEOT%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJGMEQCIH9qI%2FHFo0TFwwhZ5hnpbny3R%2BBmGbU0Q6Jf2eSs4aMwAiAg1gQKCHXgtyB1QTOz9%2BHuFdAEwUjZfZxdN7qIuitxnSqyBQgdEAUaDDA1OTAwMzU0Njg2NSIMamYY8Czn0NEpjijeKo8Fst5HNVzMqIsK6tHRy1OPd3%2BiRf4CleOwam945epwh%2BWJCRv3vjV8cHVmcUPqNnQI6CNJ%2BHjihnNnr1KKKh25j9oqm8eVOB6EPMOQmOlZ8JnfOw82gvpFwLvNDQBspUb%2FSS7qIz1LTJRkQASLgxJzjCDB2emDLOTnwBmVrktQOqTAH1A04l%2FY5xtc1GQI9emBGMXRHjBFSH2LHORJ08vvfDEMpF%2FnFWesKWqcGC9SrZdSxXgiVvnL2kX%2FA96V1%2B5AevSLvAQz2GiAfG7IjuurqeZht68BqTv%2Bi%2BRqNRIYIFbGxDzeucq3ac1xrSlaHwznp31k%2BFLwJoLLYSEixqfBpuBat%2Ft9vzhxMlcflvyteLNaP4B4EHiuQ9DixBMYQ0hKdtHXZpd7wmY1UYM9g1S4Yc6GNMjj%2BfXQWexvCOgUbqPqIjDp4WtKdPA%2B1slxuoE4wyns%2Bvqntw01MjdbU9Bn4pBQQOwS4fzz9bFlB2iDKGAKXyN0SHqdWPpP9Scj6yJuIXOsZkSS0481ADJLyUF7n46ZFuKmYSsDdy5f5RegbcmY25YITTooTxJxK0IXBczdPZIkfWAsPvBvvq%2BREarPeOA3FAcEs5%2BOSSU41qk8QJEiHdOdnTuScsjI1yMElwnepaA8DdJ9DTU3YeXpMG7xColHHCpn%2FeCeTvP612oFVjqE4Q1yqBpdCiy2CMWdvHhtXcAZOeavgMMfqhk6OWN8qXlZubu8uFiOfDwDpPWZE5qpitKaC6pwM7lkYyecPstLn84Sh149kpVnMY1aLp2NgCZ4rvq4XWwV1dMNrPeKU7GyQBwIKIBGlQz5fHPFbINPDH8UXZW7cCe%2BT02g0BXwQY4lgzqGqxyYpe3NtS7dwzD%2B%2BO29BjqyAemqzi7IVALnQ9vlrBPSO%2BkAPcisPB%2FY%2B8BmQC16wLFwu63gufdnti8i%2FsS1H%2FD%2BpPqJ3t1vn2wie%2FOc9mgRZkY8HqNqX9Dv%2FUH%2FOICaGadyLdPc8A3sjo7bPtUV42NA5FZwBt8YiikhkCFQwzTcrHzr5fP9kN9ThQVSY1DMSTz%2BMbLmLWoolWEwLwzL9mS3qEz2mX3h%2Boec4CYuKBRgExYTH0V1dk0bfca4YMPpvgER7iA%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250223T204131Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYZTUPN5RI%2F20250223%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=59057549b15a459c579302af14796c40e5c70192d93a62b69b68c2bd3942cd8b&hash=bc06cbd441c60c0f8ee395108521ce86afe847a68e5f109544b937b88a9c473c&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0896627324008821&tid=spdf-34e9b5cb-d1e9-4a56-8a8b-edab99b3d37e&sid=d752fa96683d9742086a083805b7d9da151bgxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&rh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105a50500e5e5d5c53&rr=916a0981a902c99d&cc=us  

Throughout our waking hours neural networks in our brains are processing incoming information, particularly sights and sounds, integrating those inputs with stored information, making decisions, and executing responses. Staying on task requires that we attend to the details of the task while filtering out ‘noise’.  In this episode I talk with Diego Mendoza-Halliday at the University of Pittsburgh about visual working memory – what it is, what neuronal circuits are involved, and how it works. His experiments involve recording of neuronal activity in prefrontal cortex and other brain regions while individuals are performing visual working memory tasks. His findings have revealed previously unknown mechanisms. He has demonstrated that attention and working memory involve different groups of neurons and has shown that throughout the cerebral cortex there is spectro-laminar motif of neuronal oscillation frequencies that appears to play an important role in working memory. This research is not only revealing how our brains process information in a seemingly effortless manner, but may also lead to new ways of improving human productivity and treating memory disorders. LINKS  Mendoza-Halliday lab webpage https://www.mendoza-halliday-lab.com/  Coding of perceived and memorized visual features in the prefrontal cortex https://pmc.ncbi.nlm.nih.gov/articles/PMC5461493/pdf/ncomms15471.pdf  Dissociation of neurons involved in attention and working memory https://www.cell.com/action/showPdf?pii=S0896-6273%2823%2900935-2  Spectrolaminar motif of local field power in the cerebral cortex https://pmc.ncbi.nlm.nih.gov/articles/PMC10917659/pdf/41593_2023_Article_1554.pdf Review article on working memory https://www.annualreviews.org/docserver/fulltext/psych/74/1/annurev-psych-021422-041757.pdf?expires=1739719353&id=id&accname=guest&checksum=3C2E750794D8E913C545FF401FEA62F7

Professor Thomas Hartung has made a major impact in biomedical research by developing and promoting alternatives to animal research. His efforts are leading to more ethical and efficient approaches to basic and applied research in the fields of environmental toxicology, drug development, and neuroscience. In this episode I talk with Thomas about two major flourishing technologies – brain organoids and artificial intelligence – and  how they are being rapidly incorporated into both basic and translational research.  He provides an historical perspective on the overzealous and unnecessary use of lab animals for toxicology and drug development and then delves into emerging research on ‘organoid intelligence’ and the relationships and interactions of brain organoids and AI.  A very thought-provoking conversation. LINKS Organoid Intelligence webpage: https://organoidintelligence.org/ AI and alternative texting of toxins and drugs: https://www.altex.org/index.php/altex/issue/view/166 Brain Organoids and Organoid Intelligence articles https://pmc.ncbi.nlm.nih.gov/articles/PMC10013972/pdf/frai-06-1116870.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10796793/pdf/frai-06-1307613.pdf

Someday it may be possible to restore neuronal networks that have been lost or damaged by brain injury or in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. There are as many astrocytes in the human brain as there are neurons and the astrocytes generally do not die in brain injuries and neurodegenerative disorders. Professor Magdalena Götz has shown that astrocytes can be converted directly into neurons using molecular biology technologies to manipulate a few transcription factors that switch cell fate.  These new neurons grow and form synapses with each other and can integrate into functional neuronal networks and may restore brain function. In this episode Dr. Götz talks about her pioneering work on cell reprogramming that holds great promise for the repair of neuronal networks damaged by trauma, a stroke, and neurodegenerative disorders. LINKS: Professor Götz publications on PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=magdalena+G%C3%B6tz&sort=date&size=200  Professor Götz Wikipedia page:  https://en.wikipedia.org/wiki/Magdalena_G%C3%B6tz Review article in Neuron: https://www.cell.com/action/showPdf?pii=S0896-6273%2821%2900972-7 Selected original research articles https://pmc.ncbi.nlm.nih.gov/articles/PMC11239498/pdf/41593_2024_Article_1677.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10719094/pdf/41591_2023_Article_2644.pdf https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930693-2

The Euclidean geometry that we learned in our primary education concerns man-made shapes such as rectangles, triangles, and perfect circles. However the shapes of molecules, cells, and organ systems (and their dynamic changes over time) are more complex. Some biological structures exhibit fractal geometry which is defined as “shapes and patterns that appear similar at different scales” (recursive iteration). Examples of biological structures exhibiting fractal geometry include the branches and roots of trees, blood vessels, lung airways, and the dendritic arbors of neurons. In this episode I talk with Antonio Di leva a neurosurgeon and neuroscientist at Macquarie University School of Medicine about fractal geometry and its applications to basic and clinical neuroscience. Fractal structures of neural networks optimize the energy efficiency of the brain.  Dr. Di leva talks about emerging applications of fractals to diagnosis and monitoring of neurological disorders, neurosurgery, neuroimaging, and computational intelligence. Fractal analyses are not limited to structures and can also be applied to studies of recursive features dynamic processes including neural network activity.  LINKS Dr. Di leva’s webpage: https://mqneurosurgery.com.au/prof-antonio-di-ieva/ Book ‘The Fractal Geometry of the Brain’: https://link.springer.com/book/10.1007/978-3-031-47606-8  Review articles: https://journals-sagepub-com.proxy1.library.jhu.edu/doi/full/10.1177/1073858413513927 https://journals-sagepub-com.proxy1.library.jhu.edu/doi/full/10.1177/1073858413513928