Roshan Cools: Dopamine’s Roles in Cognitive Control, Motivation, Decision-Making, ADHD, and PD
Brain Ponderings podcast with Mark Mattson
Release Date: 03/06/2025
Jonathan Long: Lactate-Phe and Ketone-Phe: Exerkines and Fastokines for Brain Health and Plasticity?
Brain Ponderings podcast with Mark Mattson
During vigorous exercise lactic acid (lactate) levels increase in the blood and during fasting and extended exercise the levels of the ketone BHB (b-hydroxybutyrate) increase. In this episode I talk with Stanford University professor Jonathan Long about his recent discovery that lactate and BHB in the blood are bound to the amino acid phenylalanine and that they (Lac-Phe and BHB-Phe) have beneficial effects on metabolic and brain health. Lac-Phe levels increase markedly in response to exercise in mice, humans, and race horses. Peripheral administration of Lac-Phe in suppresses food intake and...
info_outline
Carlos Matute: Brain White Matter in Health, Endurance Exercise, and Disease
Brain Ponderings podcast with Mark Mattson
White matter consists of bundles of long axons that convey information between neural circuits between different brain regions within and between brain hemispheres. These long axons are wrapped with many layers of lipid-rich membranes of oligodendrocytes (a type of glial cell) and it is this ‘insulation’ that enables rapid propagation of signals over long distances. The axons in white matter consume high amounts of energy and their energy demand increases during extended physical exercise. In this episode Professor Carlos Matute talks about his interesting journey to become a...
info_outline
Michael Kreutz: Amazing Nanomachines in Synapses that Keep Brains Healthy and Wise
Brain Ponderings podcast with Mark Mattson
Michael Kreutz is Head of the Neuroplasticity Research Group at the Leibniz Institute for Neurobiology in Magdeburg Germany. Using powerful high resolution microscopy and molecular biology tools his laboratory has shown that autophagy occurs within synapses. Synaptic autophagy is stimulated by neural network activity and is critical for their maintenance and for learning and memory. Moreover, evidence suggests that conventional autophagy and exocytic autophagy prevent the abnormal accumulation of pathogenic proteins (Tau, TDP43, etc.) in neurodegenerative disorders. Pharmacological and...
info_outline
Jordan Grafman: Neural Circuits of Religiosity: ‘The Kingdom of God’ is in the Prefrontal Cortex
Brain Ponderings podcast with Mark Mattson
Belief in supernatural agents and other religious myths arose as a means of ‘explaining’ the unknown and as a tool for social cohesion and hierarchical control of civilizations. Their religiosity is major feature of a ‘believers’ self identity as well as their group identity. Compelling evidence from multiple types of studies have revealed the neurobiological foundations of beliefs in imaginary deities, an afterlife, and other religious myths. In this episode neuropsychologist Jordan Grafman talks about his research and related research showing that neural circuits in the prefrontal...
info_outline
Sridevi Sarma: Using DSM and Neuro-engineering to Diagnose and Treat Neurological Disorders
Brain Ponderings podcast with Mark Mattson
Neurological disorders involve aberrant neural network activity. New technologies are needed for establishing at a fine spatial and temporal resolution the nature of the altered network activity – and for restoring activity to or towards a healthy state. Professor Sri Sarma is an electrical engineer and neuroscientist who is at the forefront of this research field. Her research combines learning theory and control systems with neuroscience to develop novel approaches for understanding normal brain function and then developing brain – computer – electrophysiology feedback control systems...
info_outline
Richard Johnson: How High Fructose Intake Induces Obesity and Chronic Diseases of the Body and Brain
Brain Ponderings podcast with Mark Mattson
Compelling evidence shows that consumption of high fructose corn syrup in soft drinks and ultraprocessed foods has contributed to the increases in obesity, diabetes, fatty liver disease, and dementia that has occurred during the past 50 years. Professor Richard Johnson’s research has been at the forefront of establishing how fructose adversely affects cellular energetics and function, and what happens to various organ systems with chronic consumption of fructose. Interestingly, cells can convert to glucose to fructose under certain conditions suggesting a roles for endogenously produced...
info_outline
Brian Kennedy: Decoding Metabolic Aging Clocks to Understand and Counteract Aging
Brain Ponderings podcast with Mark Mattson
Major progress has recently been made in understanding the aging process at the molecular, cellular, and organ system levels. This knowledge is now being applied in preventative and interventional health care. Moreover, because of the severe burden of age-related diseases on societies governments are increasingly developing strategies to extend health span throughout their populations. In this episode Professor Brian Kennedy at the National University of Singapore provides a broad perspective on the field of aging research and its translation into actionable countermeasures. He talks about...
info_outline
Anton Maximov – The Synaptic Signatures of a Memory: Zooming in Using Cutting-Edge Technology
Brain Ponderings podcast with Mark Mattson
Remarkable progress has been made towards understanding of the molecular control of neurotransmitter release from presynaptic axon terminals and the responses of the postsynaptic neuron by neurotransmitters. We know that synaptic activity is required for learning and memory but the structural basis of a memory (an engram) remains unknown. Anton Maximov has made major contributions to understanding the molecular control of synaptic plasticity associated with learning and memory. Here he talks about his research career journey which began in St. Petersburg Russia followed by postdoc...
info_outline
Allan Butterfield: Cell Membrane Lipid Peroxidation and Neuron Degeneration in Alzheimer’s Disease
Brain Ponderings podcast with Mark Mattson
The outer membrane of cells is comprised of a lipid bilayer consisting of phospholipids, cholesterol, arachidonic acid, omega-3 fatty acids, and others. Embedded in the membrane are various proteins that play roles critical to the survival and function of the cell. Examples of membrane proteins of particular importance for neurons are: ion channels and ion ‘pumps which control neuron excitability; glucose and ketone transporters which are critical for energy metabolism, and receptors for a myriad of neurotransmitters, neurotrophic factors, and other inter-cellular signaling molecules. In...
info_outline
Francesco Papaleo: Inter-brain Synchrony and Co-modulation of Neural Networks in Social Interactions
Brain Ponderings podcast with Mark Mattson
A fascinating feature of interactions between two people is that neural network activity patterns in their brain can become synchronized. In this episode Francesco Papaleo talks about research studies in which activities of neuronal networks are recorded simultaneously in interacting humans or mice. His work has recently focused on the role of interbrain synchronization in the prefrontal cortex in emotion recognition and empathy. He summarizes this research and its implications as follows: Interacting brains operate as an integrated system, with neural dynamics coevolving over...
info_outlineDopamine 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