image: Overview of the study. Researchers investigated the neural basis of how animals adapt to new environments and situations. To do this, they introduced a chemical ON/OFF switch in the orbitofrontal cortex (OFC) of macaque monkeys. In this way, they could independently silence two distinct neuronal pathways originating from the OFC; one towards the caudate and one towards the mediodorsal thalamus. Through carefully designed behavioral experiments, they determined that the OFC–caudate pathway is essential for experience-based adaptation, whereas the OFC–mediodorsal thalamus pathway is essential for inference- or knowledge-based adaptation.
Credit: Kei Oyama, QST
In a constantly changing world, animals, including humans, need to quickly adapt to their environment and learn to make decisions that lead to the best possible outcomes. In most cases, this type of learning happens through direct experience; when faced with a choice between two particular items or events, animals resort to previous experience involving the same options. However, animals with more developed brains, such as apes and monkeys, can also infer the outcome of a decision based on knowledge of similar past situations, even when they have not directly experienced those specific options before. Thus, the process of decision-making often involves a balance between experience-based and knowledge-based behavioral strategies.
In primates, the orbitofrontal cortex (OFC) region of the brain is in charge of this balancing act. It not only participates directly in decision-making, but also helps ‘update’ the internal values primates use to gauge how good an option is. Moreover, the OFC seems necessary for correctly assessing options with which an individual has no direct experience. In spite of this knowledge, the precise roles of the OFC in decision-making and whether distinct roles rely on separate neuronal pathways remain unclear, as well as quite difficult to study.
Fortunately, as reported in a paper published in Nature Communications online on August 28, 2024, a research team from Japan managed to shed light on this issue. Using a state-of-the-art approach previously developed by the team, they selectively turned on and off different neuronal pathways originating from the OFC in monkeys during newly designed behavioral tasks, revealing their independent functions. This study was led by Kei Oyama and by Group Leader Takafumi Minamimoto, both from the National Institutes for Quantum Science and Technology.
In the behavioral tasks used for the experiments, macaque monkeys had to choose between two images presented to them, and a predetermined amount of juice was given as a reward depending on the selection. Soon, the monkeys learned to associate images with the amount of juice they would receive. The researchers would periodically change the set of images presented to the animals and also reverse the reward values, making the worst options become the best and vice versa. Overall, these tasks tested the ability of monkeys to learn from experience (through trial-and-error) and tackle situations they were familiar with (through knowledge-based inference).
As monkeys performed these tasks, the researchers used a genetically introduced chemical switch, called a chemogenetic receptor, that could effectively turn neurons of the OFC on and off upon administration of a specific drug. Guided by computed tomography, positron emission tomography, and magnetic resonance imaging, the team was able to assess the effects of locally injecting a drug that temporarily silenced distinct neuronal pathways originating from the OFC.
By observing how the monkeys’ performance changed, the researchers could thus determine the functions of these pathways. They found that the OFC pathway connecting to the caudate nucleus is necessary for experience-based adaptation, whereas the OFC pathway connecting to the mediodorsal thalamus is important in knowledge-based adaptation.
Since monkey brains are surprisingly similar in structure to our own, important conclusions relevant to humans can be drawn from the findings. “One key implication of our work is that it could help explain why individuals approach the same situation in different ways. Some people may rely more on trial-and-error, while others prefer a more systematic approach based on prior knowledge,” muses Minamimoto. Adding further, he says, “These differences in thinking styles, or ‘thought patterns,’ might be linked to how each person’s brain activates these specific circuits, and understanding these variations could help us develop personalized strategies for improving decision-making and problem-solving skills for those who might struggle with one particular type of thinking.”
To add to it, understanding the precise roles of brain structures is immensely useful when investigating neuropathologies and psychiatric disorders. “Our findings could contribute to new treatments for mental and neurological disorders like obsessive-compulsive disorder, where patients have difficulty adapting to changing situations. By targeting the specific brain circuits involved in these two strategies, we may be able to create more effective therapies that help restore balanced thinking,” comments Oyama. Sharing his concluding thoughts and real-life applicability of this research, he says, “Lastly, our research has applications in AI and robotics, where this understanding of brain circuits could inspire more adaptable systems that switch between different problem-solving methods depending on the situation.”
While the brain is undoubtedly one of the biggest puzzles in the known universe, studies like this are a stepping stone towards a clearer picture of how it works under the hood, both in our heads and that of our fellow animals.
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About National Institutes for Quantum Science and Technology, Japan
The National Institutes for Quantum Science and Technology (QST) was established in April 2016 to promote quantum science and technology in a comprehensive and integrated manner. The new organization was formed from the merger of the National Institute of Radiological Sciences (NIRS) with certain operations that were previously undertaken by the Japan Atomic Energy Agency (JAEA). QST is committed to advancing quantum science and technology, creating world-leading research and development platforms, and exploring new fields, thereby achieving significant academic, social, and economic impacts.
Website: https://www.qst.go.jp/site/qst-english/
About Takafumi Minamimoto from National Institutes for Quantum Science and Technology, Japan
Dr. Takafumi Minamimoto is Group Leader of the Neural Systems and Circuits Research Group and Deputy Director of the Advance Neuroimaging Center (ANC) at the National Institutes for Quantum Science and Technology (QST) in Chiba, Japan. His research focuses on the interaction between motivation, emotion, and memory in the brain of non-human primates, using varied methods, including neuroimaging with functional MRI and PET as well as chemogenetic techniques.
About Key Oyama from National Institutes for Quantum Science and Technology, Japan
Dr. Kei Oyama is a enior researcher within the group, specializing in the study of the prefrontal cortex as a key biological foundation of human intelligence. He mainly contributes to developping cutting-edge methodology that manipulate multiple brain circuits of non-human primates, contributing to a deeper understanding of the brain mechanism in shaping intelligence.
Funding information
This study was supported by MEXT/JSPS KAKENHI Grant Numbers JP18K15353, JP21K07268, JP22H05521, JP17H02219, JP22H05157, JP19H05467, JP15K21742, and JP20H05955, by JST PRESTO Grant Numbers JPMJPR22S3 and JPMJPR2128, and by AMED Grant Numbers JP23dm0307007, JP21dm0107146, JP20dm0307021, and JP21dm0207077.
Media contact:
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Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Distinct roles of monkey OFC-subcortical pathways in adaptive behavior
Article Publication Date
24-Aug-2024
COI Statement
The authors declare no competing interests.