image:
Bananas represent the reward and the crocodile represents the risk. The blue path is a low risk-low return decision, while the pink path is a high risk-high return decision.
Credit: Trais/WPI-ASHBi
Life consists of infinite possibilities appearing in the real world as multiple choices, that then require decision-making in order to determine the best course of action. However, with every choice there also exists a certain amount of uncertainty or risk. Therefore, behind every decision, lies an intricate evaluation process that balances the risks and rewards associated with taking such actions. This can, in extreme cases, manifest itself as a pathological behavioral state of high risk-high return (HH) and low risk-low return (LL) decision processing that has been associated with gambling disorders.
Although these higher cognitive processes occur seamlessly within the cerebral cortex of our brains dozens to hundreds of times daily the exact underlying neural circuits have remained elusive due to the technical difficulties of specifically targeting and manipulating these neural circuits.
A new study published Science, from a team of researchers led by Dr. Tadashi Isa at the Institute for the Advanced Study of Human Biology (WPI-ASHBi) and Graduate School of Medicine/Kyoto University, have identified and selectively manipulated using optogenetics a method that can modulate the activity of specific neurons with light the distinct neural circuits responsible for balancing risk vs. reward-return decision-making in primates. They show the behavioral changes resulting from stimulating these circuits accumulate over time and have long-term consequences independent of any stimulus providing insights into potential mechanisms underlying pathological risk-taking behaviors such as gambling disorders.
Various experimental paradigms have been developed to evaluate decision-making behavior, with the Iowa Gambling Task being arguably the most famous. However, such neuropsychological tasks are often limited by their design, as they cannot sufficiently uncouple higher-order cognitive processes.
To determine the pure choice bias between HH and LL decisions, Isa and colleagues first designed their own decision paradigm to uncouple risk-dependent choice behavior from other higher-order cognitive processes. Using eye movement to indicate their choice, macaque monkeys were trained to perform a cue/target choice task with water as their reward, consisting of 5 different HH-LL choices across 5 different sets of equivalent expected value (volume of reward awarded multiplied by probability), making a total of 25 potential options. Consistent with other primate studies that looked at risk-behavior, the authors found that primates had an inherent bias for HH over LL choices.
In the early 20th century, the cerebral cortex was mapped into 52 regions, known as Brodmann areas, based on their distinct cellular morphology and organization. The deeper, or ventral, parts of Brodmann area 6 (area 6V), were long thought to only function as a motor area in humans and primates. But more recently, regions overlapping area 6V have also been associated with decision-making processes, though direct evidence supporting such a function has been lacking.
By pharmacologically inactivating several candidate frontal brain regions, using the selective GABAA receptor agonist muscimol, the authors found that the ventral part of area 6V (area 6VV) to be responsible for the HH choice behavior. Interestingly, despite the orbitofrontal cortex (OFC) and the dorsal anterior cingulate cortex (aACC) being considered to play central roles in reward-based decision-making in monkeys, inactivating these regions had little effect on preference for HH choice.
Indeed, we were really surprised that neither the OFC nor the aACC were important for risk-dependent decision-making comments Dr. Ryo Sasaki, the first author of the study.
The ventral tegmental area (VTA) of the brain is essential for reward-associated processes, which is integral to risk-related decision-making. A subpopulation of dopaminergic neurons residing in the VTA are connected to the prefrontal cortex, including area 6V, also known as the mesofrontal (or the mesocortical) pathway.
To dissect the specific role of the mesofrontal pathway in risk-dependent decision-making, Isa and collaborators used an elegant optogenetic strategy, whereby an array consisting of 29 LED lights coupled to electrocorticogram (ECoG) electrodes was engineered (dimensions: 19mm x 12mm) and implanted into area 6V of primate brains expressing photoactivatable proteins in VTA neurons. During the narrow time window of decision-making, the authors precisely manipulated the neural activity of defined VTA terminals in area 6V by turning ON specific LEDs in their array, while simultaneously recording the activity within area 6V, that also included more superficial, or dorsal regions (area 6VD; approximately 2-3mm above area 6VV). The authors uncovered two subcircuits within the mesofrontal pathway with distinct roles in risk-dependent decision-making. They found HH-preference was dependent on the VTA-6VV pathway, whereas LL preference was dependent on the VTA-6VD pathway.
The spatiotemporal resolution of our LED/ECoG array was essential in distinguishing the VTA-6VV and VTA-6VD pathways and deciphering their distinct functional roles in risk-dependent decision-making claims Sasaki.
These findings were further validated by computational decoding, which recapitulated the choice preference behavior induced by photostimulation in primates in silico.
Interestingly, upon repetitive stimulation of either the VTA-6VV or the VTA-6VD pathways, Isa and coauthors observed cumulative effects that persisted over time, leading to long-term changes in preference for HH and LL choice in primates, respectively independent of any photostimulation. Isa comments, ...such long-term changes in choice behavior were rather unexpected and he adds, ... but this may now also offer a mechanistic explanation for how gambling disorders arise.
Exactly how these distinct circuits contribute to balancing our day-to-day decision-making remains unclear, but the authors believe other brain regions are likely to also contribute to this process.
Considering the similarities (in structure and function) between human and non-human primate brains, our findings may have potential therapeutic implications, and even applications in the future, for the treatment of pathological forms of risk-taking such as gambling disorders, he says.
These findings were published in Science on January 5th 2024.
By
Spyros Goulas, Ph.D.
Scientific Advisor
Institute for the Advanced Study of Human Biology (WPI-ASHBi) / Kyoto University
Email: goulas.spyros.3n@kyoto-u.ac.jp
First/Corresponding Author of Study
Ryo Sasaki, Ph.D.
Assistant Professor
Department of Neuroscience, Graduate School of Medicine / Kyoto University
Email: sasaki.ryo.3r@kyoto-u.ac.jp
Lead Principal Investigator/Corresponding Author of Study
Tadashi Isa, M.D., Ph.D.
Professor
Department of Neuroscience, Graduate School of Medicine
Institute for the Advanced Study of Human Biology (WPI-ASHBi) / Kyoto University
Email: isa.tadashi.7u@kyoto-u.ac.jp
###
About Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University
What key biological traits make us human, and how can knowing these lead us to better cures for disease? ASHBi investigates the core concepts of human biology with a particular focus on genome regulation and disease modeling, creating a foundation of knowledge for developing innovative and unique human-centric therapies.
About the World Premier International Research Center Initiative (WPI)
The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).
Experimental study
Animals
Balancing risk-return decisions by manipulating the mesofrontal circuits in primates
5-Jan-2024
Continue reading here:
Lighting the circuits to risky decision-making - EurekAlert
- Challenging Viral Biology: Researchers Discover Mysterious Virus With Ribosomal Protein - SciTechDaily - January 1st, 2025 [January 1st, 2025]
- Insights into the biology and insecticide susceptibility of the secondary malaria vector Anopheles parensis in an area with long-term use of... - January 1st, 2025 [January 1st, 2025]
- Artificial Intelligence in Biology: From Neural Networks to AlphaFold - The Scientist - January 1st, 2025 [January 1st, 2025]
- Visiting Clinical Assistant Professor of Biology, Department of Biology - The Chronicle of Higher Education - December 23rd, 2024 [December 23rd, 2024]
- Medicinal Plant Biology Successfully Indexed in We | Newswise - Newswise - December 23rd, 2024 [December 23rd, 2024]
- Biology professor leads team authoring article on notable marine microbe - https://alvernia.edu - December 23rd, 2024 [December 23rd, 2024]
- The perfect pair: How biology and engineering are creating new breakthroughs in human health - National Heart, Lung, and Blood Institute - December 23rd, 2024 [December 23rd, 2024]
- Read Some of the Most Exciting Stories From the Smithsonian Conservation Biology Institute in 2024 - Smithsonian Magazine - December 23rd, 2024 [December 23rd, 2024]
- Renovated biology lab inspires learning and collaboration - IU Newsroom - November 28th, 2024 [November 28th, 2024]
- New approach in amphibian biology: harmless viruses help to study the nervous system of frogs - European Research Council - November 28th, 2024 [November 28th, 2024]
- Space Biology, Tech Studies Fill Day as Station Boosts Orbit - NASA Blogs - November 28th, 2024 [November 28th, 2024]
- Johns Hopkins professor delivers lecture on breakthrough reproductive biology research - Liberty News - November 28th, 2024 [November 28th, 2024]
- Dr. Yvette Mercer relates her biology lessons to the real-world at Windsor Forest High School - WJCL News Savannah - November 28th, 2024 [November 28th, 2024]
- Discovery of a universal brain function: from biology to AI? - Techno-Science - November 28th, 2024 [November 28th, 2024]
- Biology Beyond the Classroom: Belize Study Abroad Course Offers Hands-On Experience College of Arts & Sciences - UofL Today - November 20th, 2024 [November 20th, 2024]
- A climate fund is way too generic, says Nucleus Capital - as it launches 40m fund focused on synthetic biology - Sifted - November 20th, 2024 [November 20th, 2024]
- WSU part of consortium exploring biology in space - WSU News - November 20th, 2024 [November 20th, 2024]
- Singleron Joins Forces with TOMY Digital Biology to Transform Single Cell Analysis in Japan - BSA bureau - November 20th, 2024 [November 20th, 2024]
- Saturday Citations: Cold dark matter takes a hit; a new paradigm for biology; those fracking earthquakes - Phys.org - November 20th, 2024 [November 20th, 2024]
- Breaking Down Molecules: Structural Biology's Big Innovations - openPR - November 20th, 2024 [November 20th, 2024]
- U of G Students Dive Into Learning in Unforgettable Marine Biology Course - University of Guelph News - November 20th, 2024 [November 20th, 2024]
- John Connolly Mad Hatter Q&A: "I had vague ambitions to be a vet, hampered slightly by Synge Street CBS refusing to teach us biology" - hotpress.com - November 20th, 2024 [November 20th, 2024]
- NMSU research team focuses on cancer biology through partnership, increase underrepresented student research - NMSU Newsroom - November 12th, 2024 [November 12th, 2024]
- Sea angels and devils: could plankton unlock the secrets of human biology? - The Guardian - November 12th, 2024 [November 12th, 2024]
- Synthetic Biology Market to Hit USD 31.52 Billion by 2029 with 20.6% CAGR | MarketsandMarkets - PR Newswire - November 12th, 2024 [November 12th, 2024]
- How ecDNA Fuels Cancer by Breaking the Laws of Biology - Howard Hughes Medical Institute - November 12th, 2024 [November 12th, 2024]
- Research Spotlight: Biology and Environmental Science, Psychology, and Religious Studies Faculty to Present Current Projects - Sherman Denison Herald... - November 12th, 2024 [November 12th, 2024]
- Symmetry in biology: A look into how bees actively organize nests in mirroring patterns - Phys.org - November 12th, 2024 [November 12th, 2024]
- UKRI invests 5.8m in engineering biology - Research Professional News - November 12th, 2024 [November 12th, 2024]
- HTAN Members Deliver Wealth of Tumor Biology Insights - Inside Precision Medicine - November 12th, 2024 [November 12th, 2024]
- Tenure-Track: Assistant Professor in Marine Biology job with Texas A&M University - Galveston | 37740878 - The Chronicle of Higher Education - October 26th, 2024 [October 26th, 2024]
- Teaching Assistant/Associate Professor, Chemistry and Chemical Biology - The Chronicle of Higher Education - October 26th, 2024 [October 26th, 2024]
- Emerging strategies to investigate the biology of early cancer - Nature.com - October 26th, 2024 [October 26th, 2024]
- Future Medicine: Physics, Biology, And AI Will Transform Human Health - Forbes - October 26th, 2024 [October 26th, 2024]
- NATIONAL VIEW: When AI looked at biology, the result was astounding - Odessa American - October 26th, 2024 [October 26th, 2024]
- Can We Pick Winners With Causal Human Biology? Vertex Makes the Case - Timmerman Report - October 26th, 2024 [October 26th, 2024]
- What Remains of Edith Finch Developers Next Game is About the Wonders and Horrors of Biology&... - GamingBolt - October 26th, 2024 [October 26th, 2024]
- Castle Biosciences to Support the 71st Annual Montagna Symposium on the Biology of the Skin - BioSpace - October 13th, 2024 [October 13th, 2024]
- 'Where we are today in biology AI is similar to GPT in 2020': An interview with the CEO of Africa's biggest AI startup - TechCrunch - October 13th, 2024 [October 13th, 2024]
- Bruker spools up spatial biology division from NanoString, Canopy assets - Fierce Biotech - October 13th, 2024 [October 13th, 2024]
- Enhanced efficiency in the bilingual brain through the inter-hemispheric cortico-cerebellar pathway in early second language acquisition |... - October 13th, 2024 [October 13th, 2024]
- Recursions Fast-Track Road to Therapeutics Using AI-Based Maps of Biology - Genetic Engineering & Biotechnology News - October 13th, 2024 [October 13th, 2024]
- The Biology of 'Precancer': Stopping Cancer Before It Starts - Medscape - October 13th, 2024 [October 13th, 2024]
- URMC Researcher wins 2024 Albany Medical Center Prize in Medicine and Biology - 13WHAM-TV - October 13th, 2024 [October 13th, 2024]
- Opinion | When AI looked at biology, the result was astounding - The Washington Post - October 13th, 2024 [October 13th, 2024]
- Castle Biosciences to Support the 71st Annual Montagna Symposium on the Biology of the Skin - Business Wire - October 13th, 2024 [October 13th, 2024]
- Inside the ISS: Astronauts Push the Limits of Biology As Crew-8 Departure Looms - SciTechDaily - October 13th, 2024 [October 13th, 2024]
- Implications of RNA pseudouridylation for cancer biology and therapeutics: a narrative review - Journal of Translational Medicine - October 13th, 2024 [October 13th, 2024]
- The fruit fly revolutionized biology. Now its boosting science in Africa - Science News Magazine - October 2nd, 2024 [October 2nd, 2024]
- Richard Dawkins on biology, genes and his 38-year-old girlfriend - The Times - October 2nd, 2024 [October 2nd, 2024]
- Smithsonians National Zoo and Conservation Biology Institute Repatriates Kiwi Feathers to New Zealand - Smithsonian's National Zoo and Conservation... - October 2nd, 2024 [October 2nd, 2024]
- CWRU debuts state-of-the-art biology laboratory classrooms and collaborative spaces - The Daily | Case Western Reserve University - October 2nd, 2024 [October 2nd, 2024]
- Biology professor honored with Award of Excellence for his contributions to algae research - University of Alabama at Birmingham - October 2nd, 2024 [October 2nd, 2024]
- Ohio Northern University Hosts Mock Crime Scene Investigation with Forensic Biology and Nursing Students - WKTN Radio - October 2nd, 2024 [October 2nd, 2024]
- UWO alumnus, biology researcher is featured guest on prominent science podcast - UW Oshkosh Today - October 2nd, 2024 [October 2nd, 2024]
- Biology Students experience international research through RISE Fellowship Grant - Illinois State University News - October 2nd, 2024 [October 2nd, 2024]
- New chairperson to diversify research in biochemistry and molecular biology - University of Nevada, Reno - October 2nd, 2024 [October 2nd, 2024]
- Discover Magazine Speaks with Biology Professor Bruce Robertson About Evolutionary Traps - Bard College - October 2nd, 2024 [October 2nd, 2024]
- Creature Feature: Meet the "Freshwater Giant" Arapaima - Smithsonian's National Zoo and Conservation Biology Institute - October 2nd, 2024 [October 2nd, 2024]
- A Quiet Revolution: The Global Race to Control Human Biology and Its Implications - HSToday - October 2nd, 2024 [October 2nd, 2024]
- Improving biology education here, there, and everywhere - MIT News - September 23rd, 2024 [September 23rd, 2024]
- 'It smells like a food bin that's overflowing': The weird biology of the giant smelly 'corpse plant' - BBC.com - September 23rd, 2024 [September 23rd, 2024]
- Instructional Professor (Open Rank) in Computational Biology - The Chronicle of Higher Education - September 23rd, 2024 [September 23rd, 2024]
- UFs Rob Ferl and Anna-Lisa Paul Talk About Blue Origin Spaceflight and Space Biology Experiments - WUFT - September 23rd, 2024 [September 23rd, 2024]
- New Alzheimer's studies reveal disease biology, risk for progression and the potential for a novel blood test - Medical Xpress - September 23rd, 2024 [September 23rd, 2024]
- David Rubenstein Donates $10 Million to Smithsonians National Zoo and Conservation Biology Institutes Giant Panda Program - Smithsonian Institution - September 23rd, 2024 [September 23rd, 2024]
- Optimization: A Theoretical Principle That Is Predictive for Biology - Discovery Institute - September 23rd, 2024 [September 23rd, 2024]
- SOMETHING FISHY: CSUB biology professors find hundreds of dead fish in dry Kern River - MSN - September 15th, 2024 [September 15th, 2024]
- Star Trek Changes Its Iconic Tribbles Forever, With Shock Revelation About Their Biology - Screen Rant - September 15th, 2024 [September 15th, 2024]
- Penn's Biology Department removes concentrations, prompting mixed reactions from students - The Daily Pennsylvanian - September 15th, 2024 [September 15th, 2024]
- Google DeepMind And Isomorphic Labs Are Making Rapid Progress In Biology And Drug Discovery - Forbes - September 15th, 2024 [September 15th, 2024]
- Bridging biology and art: An interview with Nigerian artist Samuel Ubong - Global Voices - September 15th, 2024 [September 15th, 2024]
- SOMETHING FISHY: CSUB biology professors find hundreds of dead fish in dry Kern River - KERO 23 ABC News Bakersfield - September 15th, 2024 [September 15th, 2024]
- From the marriage of physics and biology emerged a technology that has revolutionised ophthalmology laser - The Hindu - September 2nd, 2024 [September 2nd, 2024]
- Groves named head of developmental biology - Washington University School of Medicine in St. Louis - September 2nd, 2024 [September 2nd, 2024]
- John Callaghan, biology professor at USC Dornsife, served as university marshal for 30 years - USC Dornsife College of Letters, Arts and Sciences - September 2nd, 2024 [September 2nd, 2024]
- Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology... - September 2nd, 2024 [September 2nd, 2024]
- A frugal CRISPR kit for equitable and accessible education in gene editing and synthetic biology - Nature.com - August 5th, 2024 [August 5th, 2024]
- UM Announces $5 Million Endowment to Create Chair in Fisheries Science for Wildlife Biology Program - University of Montana - August 5th, 2024 [August 5th, 2024]
- New Insights into MaleFemale Biology from Platypus and Chicken Chromosomes - Technology Networks - August 5th, 2024 [August 5th, 2024]