計算行動神経科学研究室　Computational Behavioral Neuroscience Lab

Research Topics

1. 1.Neural mechanisms of delay discounting

   Reinforcement learning, a theoretical framework in which optimal behavior is learned by trial and error through interaction with the environment, has been proposed as a computational model of decision-making in animals, including humans. To elucidate the neural mechanisms involved in reward prediction, we conducted fMRI, a non-invasive functional brain imaging technique, on healthy participants and analyzed behavioral and brain activity data in a Markov decision problem for long-term and short-term reward prediction using a reinforcement learning model. The results revealed that the ventral part of the cortico-striatal circuit is involved in the prediction with a large discount rate, and the dorsal part is in the prediction with a small discount rate, indicating that the brain performs reward prediction with different discount rates in parallel.

   Tanaka, S. C., Doya, K., Okada, G., Ueda, K., Okamoto, Y., & Yamawaki, S. (2004). Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops. Nature neuroscience, 7(8), 887–893. https://doi.org/10.1038/nn1279

   

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2. 2.Delay discounting and serotonin

   Previous studies have reported that serotonin, a brain substance, is involved in time discounting, mainly in animal experiments using rats, but consistent results have yet to be obtained in humans. To investigate the relationship between discount rates and serotonin, we developed an intertemporal choice task in which participants choose between a small immediate reward and a large, time-consuming reward and measured and analyzed their behaviors and brain activities during the task while artificially adjusting the level of serotonin in their brains. The results showed that when serotonin levels were normal, multiple discount rates of reward prediction were distributed from ventral to dorsal regions of the striatum, which is consistent with previous studies. On the other hand, we found that the ventral part of the striatum was predominant when serotonin was low, and the dorsal part of the striatum was predominant when serotonin was high, indicating that the activity of the striatum is affected by the action of serotonin.

   Tanaka, S. C., Schweighofer, N., Asahi, S., Shishida, K., Okamoto, Y., Yamawaki, S., & Doya, K. (2007). Serotonin differentially regulates short- and long-term prediction of rewards in the ventral and dorsal striatum. PloS one, 2(12), e1333 https://doi.org/10.1371/journal.pone.0001333

   

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3. 3.Altered delay discount and problematic behavior

   Delay discounting is a topic of economics study and has recently been pointed out to be related to social and health problems such as multiple debts and obesity. It has also been used as a model of impulsivity, a symptom of psychiatric disorders, and a behavioral trait of adolescents. Therefore, we clarify the relationship between the parameters of the decision-making model and problematic behaviors and contribute to the understanding and preventing social and health problems. In response to an economic study showing that people with a high discount rate and no asymmetry in the discount rate between rewards and losses (sign effect) have higher rates of multiple debts and obesity, we conducted an experiment to elucidate the brain mechanism of the sign effect. In an experiment using the intertemporal choice between rewards and losses task, we estimated the discount rate from the subjects' behavioral data and compared the brain activities of the groups with and without the sign effect (asymmetry of the time discount rate between rewards and losses in behavior). The results suggest that the asymmetry of reward and loss in striatal activity is caused by the sign effect, i.e., the asymmetry of reward and loss in behavior.

   Tanaka, S. C., Yamada, K., Yoneda, H., & Ohtake, F. (2014). Neural mechanisms of gain-loss asymmetry in temporal discounting. The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(16), 5595–5602. https://doi.org/10.1523/JNEUROSCI.5169-12.2014

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4. 4.Temporal credit assignment and serotonin

   The impulsive choice to frequently select "small immediate rewards" in intertemporal choice occurs when the weight of delayed rewards is reduced when the discount rate is high, but it can also occur when delayed rewards obtained in learning are only associated with the immediate past (credit assignment problem). To test this, we estimated the decay rate of subjects' temporal credit assignment from their behaviors in a learning task in which there is a temporal delay between the past action and the current reward under the serotonin level is manipulated. We found that the decay rate of the temporal credit assignment to the loss was larger when the serotonin level was decreased than in the normal condition. These results suggest that serotonin is involved in both the future time scale (discount rate of reward prediction) and the past time scale (decay rate of temporal credit assignment).

   Tanaka, S. C., Shishida, K., Schweighofer, N., Okamoto, Y., Yamawaki, S., & Doya, K. (2009). Serotonin affects association of aversive outcomes to past actions. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29(50), 15669–15674. https://doi.org/10.1523/JNEUROSCI.2799-09.2009

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5. 5.Data-driven approach

   Computational psychiatry has gained momentum, in which the mechanisms of psychiatry disorders are understood as computational models by applying the hypothesis-testing approach to patients with psychiatry disorders, as described in topics 3 and 4 above. On the other hand, the data-driven approach, which combines multivariate brain and behavioral data with machine learning, is attempting to understand the mechanisms of psychiatry disorders and individual characteristics in a "holistic" manner without being bound by any specific hypothesis. Examples of such approaches include identifying disorders using resting-state functional connectivity patterns, biotype identification, and prediction of individual characteristics. However, data-driven analysis with high accuracy and generalization performance requires a large amount of data and the development of algorithms to extract features successfully. The applicant has elucidated the brain network common to various types of anxiety by using large data sets and practical machine learning algorithms tailored to the characteristics of each data set. By extracting features from brain activity data reflecting different types of anxiety, i.e., brain activity during anxiety-provoking tasks and resting-state brain activity related to daily anxiety characteristics, and reducing the dimension of the features, we identified the brain network common to these types of anxiety. We developed a method for identifying patients with anxiety-related diseases from this brain network. We confirmed that it is possible to discriminate patients with anxiety-related disorders from this brain network.

   Takagi, Y., Sakai, Y., Abe, Y., Nishida, S., Harrison, B. J., Martínez-Zalacaín, I., Soriano-Mas, C., Narumoto, J., & Tanaka, S. C. (2018). A common brain network among state, trait, and pathological anxiety from whole-brain functional connectivity. NeuroImage, 172, 506–516. https://doi.org/10.1016/j.neuroimage.2018.01.080

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6. 6.Computational model of obsessive-compulsive disorder

   We use computational models to describe human behavior and investigate the relationship between the parameters, individual characteristics, and neural mechanisms. Specifically, we are constructing computational models of psychiatric disorders and validating them with empirical data. We model obsessive-compulsive disorder (OCD) symptoms as implicitly learned maladaptive behaviors. Simulations in the reinforcement learning framework show that agents implicitly learn to respond to intrusive thoughts when the memory trace signal for past actions decays differently for positive and negative prediction errors. Moreover, this model extends our understanding of the therapeutic effects of behavioral therapy in OCD. Using empirical data, we confirm that patients with OCD show extremely imbalanced traces, which are normalized by serotonin enhancers. We find that healthy participants also vary in their obsessive-compulsive tendencies, consistent with the degree of imbalanced traces. These behavioral characteristics can be generalized to variations in the healthy population beyond the spectrum of clinical phenotypes.

   Sakai, Y., Sakai, Y., Abe, Y., Narumoto, J., & Tanaka, S. C. (2022). Memory trace imbalance in reinforcement and punishment systems can reinforce implicit choices leading to obsessive-compulsive behavior. Cell reports, 40(9), 111275. https://doi.org/10.1016/j.celrep.2022.111275

   

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7. 7.Large-scale neuroimaging database

   Recently, the reproducibility of results of scientific research has become a major issue in scientific fields as a whole, and various attempts have been made to ensure reproducibility in brain research. Among them, large-scale data collection and sharing are considered the most important to ensure sufficient statistical power. As a member of the multi-institutional human brain MRI large-scale database project, we have constructed a globally valuable multicenter and multi-disease brain MRI database that is publicly available.

   Tanaka, S. C., Yamashita, A., Yahata, N., Itahashi, T., Lisi, G., Yamada, T., Ichikawa, N., Takamura, M., Yoshihara, Y., Kunimatsu, A., Okada, N., Hashimoto, R., Okada, G., Sakai, Y., Morimoto, J., Narumoto, J., Shimada, Y., Mano, H., Yoshida, W., Seymour, B., … Imamizu, H. (2021). A multi-site, multi-disorder resting-state magnetic resonance image database. Scientific data, 8(1), 227. https://doi.org/10.1038/s41597-021-01004-8

   

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