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Doya, K.

Publications and source records attributed to Doya, K..

13 recordsLinked to original sources

Transition from model-free to structure-informed decision making in dynamic environments

Reinforcement learning theory formulates distinct decision-making strategies, including reactive model-free and deliberative model-based strategies. This study investigates how mice adjust their reinforcement learning strategies while learning decision-making in dynamic environments. Unlike previous studies that focused on behaviors after extensive training periods, we analyzed changes in learning strategies in the course of training of a two-step decision-making task with probabilistic state transition and fluctuating reward probabilities. Our statistical behavioral analysis showed that the stay-probability following common and rare transitions diverged with training, a signature of strategies that utilize knowledge of task structure. We fit various reinforcement learning strategies to behavioral data and found that structure-informed strategies became increasingly dominant in their behaviors during training. Whereas previous studies emphasized transition from goal-directed to habitual strategies after extensive training, which were often associated with model-based and model-free strategies, respectively, our results newly demonstrate a shift from model-free to structure-informed strategies in early training in mice. Author summaryReinforcement learning theory allows us to examine how we make decisions and what approaches we use to optimize rewards. Most previous research, however, has examined animal behavior only after extensive training. Here we analyzed how mice adjust their reinforcement learning strategies as they are trained in a two-step decision-making task. Initially, mice relied on reactive model-free strategies, but as training progressed, their behavior began to incorporate knowledge of task structure. While previous studies suggested transition from model-based to model-free strategies with extensive training, our study revealed the opposite in the early stage of training.

animal behavior and cognition↗

Continuous Strategy Adaptation and Discrete Switching Driven by Environment and Internal State in Meta-Learning

AO_SCPLOWBSTRACTC_SCPLOWBehavioral strategies can change in response to environmental and internal states, either gradually or abruptly, enabling flexible adaptation. Such strategy regulation is central to meta-learning, the ability to learn to learn. Previous studies analyzed temporal or condition-dependent strategy change using models and theories that assume continuous or discrete changes. Here, we analyze the mices behavior in a two-step decision task using four different approaches: stay-switch choice probability analysis; generalized linear mixed model (GLMM) of choice and reaction time (RT) given preceding task events; fitting a reinforcement learning (RL) model with time-varying meta-parameter by a novel multiple-step particle filtering method; and fitting a finite internal state (FIS) model that produces choice and RT depending on discrete state transition. Together, the stay probability and GLMM analyses reveal that learning progress encourages a shift toward a model-based, value-based learning strategy, accompanied by elevated choice perseveration. More uncertain reward settings or changes in them lead to random, exploratory behavior. Meta-parameter dynamics show faster learning, greater involvement of a model-based strategy, higher choice stochasticity, and more rapid development of choice perseveration with less contribution to the final decision as learning progresses. Exploratory behavior in the face of uncertain reward settings or changes in those settings is underpinned by slower forgetting and greater model-based contribution. FIS modeling discovered a trial-level switch between an optimal value-based learning state and a suboptimal self-repeating state. Meta-parameter dynamics reflect continuous strategy changes, while state transitions capture abrupt, discrete strategy switches. At an intermediate timescale, when reward settings change, two processes interact: mice persist in a self-repeating state, leading to attempts at model-based strategy with incomplete adaptation.

animal behavior and cognition↗

Pan-cortical area sensorimotor network coordination during motor learning of forelimb-reaching task in the marmoset

Motor learning alters activities in multiple brain areas. While learning-induced activity change in these areas has been investigated, how the information flow changes in the network across those areas remains to be thoroughly examined. We analysed wide-field calcium imaging data spanning from the premotor cortex to the parietal cortex of marmosets while they learned a two-target forelimb-reaching task. We applied non-negative matrix factorization (NMF) to the activity data and extracted about 30 localized activity components. Encoding model analysis indicated that learning was associated with a decrease in activity components related to hand movements, and an increase in those related to external and reward signals. Causality analysis by embedding entropy (EE) revealed increases in causal links across activity components in different areas and stabilization of the network structure with behavioural improvements. These results indicate that motor learning entails both a redistribution of task-related activity and a reorganization of large-scale cortical network interactions.

neuroscience↗

Topological basal ganglia model with dopamine-modulated spike-timing-dependent plasticity reproduces reinforcement learning, discriminatory learning, and neuropsychiatric disorders

The basal ganglia (BG) are central to action selection and reinforcement learning, yet how the topological organization of the BG circuit with dopamine (DA) D1- and D2-receptors shape learning remains unclear. We present a topologically organized spiking model of macaque BG with cortico-striatal inputs organized into competing channels, D1/D2 medium spiny neurons (MSNs), three-factor DA-modulated STDP for cortical synapses, asymmetric intra-striatal collaterals, and partially overlapping direct/indirect pathways. We validate resting activity and action selection, then study conditioning and generalization-discrimination learning using DA bursts (CS+) and dips (CS). Two structural determinants emerged. First, pathway overlap ({lambda}) trades off selection efficiency and learning speed: higher overlap degrades GPi-based selection efficiency during conditioning, yet accelerates convergence during discrimination by strengthening D2 influence on GPi. Second, lateral inhibition from MSN-D2 to MSNs ({kappa}) helps constrain competing actions but is not sufficient alone; robust discrimination requires DA-dip-dependent up-modulation of D2 collateral efficacy (), which speeds and, at low overlap, enables convergence. Simulations under Parkinsonian and schizophrenia-like settings showed different deficits. A hypodopaminergic "Parkinsonian" STDP regime (D1 LTP loss, D2 LTD loss) impaired conditioning and failed to enhance discrimination. In contrast, attenuated D2 plasticity during DA dips (modeling methamphetamine-induced changes/schizophrenia-related dysregulation) selectively disrupted discrimination while sparing conditioning. Finally, we demonstrate efficient scaling on the Fugaku supercomputer to rodent and non-human primate-relevant sizes, supporting large-scale, biologically grounded BG simulations. Together, the results highlight how pathway overlap and D2 collateral dynamics jointly regulate the speed and reliability of discrimination learning, and how specific DA perturbations map to distinct learning impairments.

neuroscience↗

Fictive Learning in Model-based Reinforcement Learning by Generalized Reward Prediction Errors

Reinforcement learning (RL) is a normative computational framework to account for reward-based learning. However, widely used RL models, including Q-learning and its variants, fail to capture some key behavioral phenomena observed in animal experiments, particularly the dynamic switch between model-free and model-based control in the two-step task. A fundamental discrepancy is that learning is restricted to experienced outcomes in the models, whereas biological agents may generalize learning to unvisited options based on internal world models, so-called fictive learning. We propose a simple, brain-inspired fictive learning rule and conduct the rodent two-step task to examine whether fictive learning could explain the observed behavior. The learning rule uses a generalized reward prediction error to update both experienced and non-encountered states and actions. The factual prediction error is scaled by the event correlation inferred from the internal model for fictive update. The generalized reward prediction error might be supported by brain-wide dopaminergic broadcasting. Through simulations, we show that this model reproduces key behavioral traits in the two-step task, including stay probabilities and regression analysis, which common RL models fail to explain. Model fitting validates its superior fit over existing alternatives. Furthermore, the model replicates dopaminergic dynamics observed in the same task. This framework bridges normative RL theory and biological learning, offering new insights into adaptive behavior.

animal behavior and cognition↗

Optical Neuroimage Studio (OptiNiSt): intuitive, scalable, extendable framework for optical neuroimage data analysis

Advancements in calcium indicators and optical techniques have made optical neural recording a common tool in neuroscience. As the volume of optical neural recording data grows, streamlining the data analysis pipelines for image preprocessing, signal extraction, and subsequent neural activity analyses becomes essential. There are a number of challenges in optical neural data analysis. 1) The quality of original and processed data needs to be carefully examined at each step. 2) As there are numerous image preprocessing, cell extraction, and activity analysis algorithms, each with pros and cons, experimenters need to implement or install them to compare and select optimal methods and parameters for each step of processing. 3) To ensure the reproducibility of the research, each analysis step needs to be recorded in a systematic way. 4) For data sharing and meta-analyses, adoption of standard data formats and processing protocols is required. To address these challenges, we developed Optical Neuroimage Studio (OptiNiSt) (https://github.com/oist/optinist), a framework for intuitively creating calcium data analysis pipelines that are scalable, extendable, and reproducible. OptiNiSt includes the following features. 1) Researchers can easily create analysis pipelines by selecting multiple processing modules, tuning their parameters, and visualizing the results at each step through a graphic user interface in a web browser. 2) In addition to common analytical tools that are pre-installed, new analysis algorithms in Python can be easily added. 3) Once a processing pipeline is designed, the entire workflow with its modules and parameters are stored in a YAML file, which makes the pipeline reproducible and deployable on high-performance computing clusters. 4) OptiNiSt can read image data in a variety of file formats and store the analysis results in NWB (Neurodata Without Borders), a standard data format for data sharing. We expect that this framework will be helpful in standardizing optical neural data analysis protocols.

neuroscience↗

The differential effect of optogenetic serotonergic manipulation on sustained motor actions and stationary waiting for future rewards in mice

Serotonin is an essential neuromodulator that affects behavioral and cognitive functions. Previous studies have shown that activation of serotonergic neurons in the dorsal raphe nucleus (DRN) promotes patience to wait for future rewards. However, it is still unclear whether serotonergic neurons also regulate persistence to act for future rewards. Here we used optogenetic activation and inhibition of DRN serotonergic neurons to examine their effects on sustained motor actions for future rewards. We trained mice to perform stationary waiting and repeated lever-pressing tasks with variable reward delays and tested effects of optogenetic activation and inhibition of DRN serotonergic neurons on task performance. Interestingly, in the lever-pressing task, mice tolerated longer delays as they repeatedly pressed a lever than in the stationary waiting task, suggesting that lever-pressing actions may not simply be costly, but may also be subjectively rewarding. Optogenetic activation of DRN serotonergic neurons prolonged waiting in the stationary waiting task, consistent with previous studies, but it did not affect lever pressing time or numbers. While optogenetic inhibition decreased waiting, it did not affect lever pressing time or numbers. In generalized linear model analysis that incorporated the time during each session and the number of sessions, however, optogenetic activation negatively affected the number and the speed of lever pressing. These results revealed that the necessity of motor actions may increase motivation for delayed rewards and that DRN serotonergic neurons more significantly promote stationary waiting rather than persistent motor actions for future rewards.

animal behavior and cognition↗

Information Dynamics of the Heart and Respiration Rates: a Novel Venue for Digital Phenotyping in Humans

In recent decade, wearable digital devices have shown potentials for the discovery of novel biomarkers of humans physiology and behavior. Heart rate (HR) and respiration rate (RR) are most crucial bio-signals in humans digital phenotyping research. HR is a continuous and non-invasive proxy to autonomic nervous system and ample evidence pinpoints the critical role of respiratory modulation of cardiac function. In the present study, we recorded longitudinal (up to 6 days, 4.63 {+/-} 1.52) HR and RR of 89 freely-behaving human subjects (Female: 39, age 57.28 {+/-} 5.67, Male: 50, age 58.48 {+/-} 6.32) and analyzed their HR and RR dynamics using linear models and information theoretic measures. While the predictability by linear autoregressive (AR) showed correlation with subjects age, an information theoretic measure of predictability, active information storage (AIS), captured these correlations more clearly. Furthermore, analysis of the information flow between HR and RR by transfer entropy (i.e., HR [->] RR and RR [->] HR) revealed that RR [->] HR is correlated with alcohol consumption and exercise habits. Thus we propose the AIS of HR and the transfer entropy RR [->] HR as two-dimensional biomarkers of cardiorespiratory physiology for digital phenotyping. The present findings provided evidence for the critical role of the respiratory modulation of HR, which was previously only studied in non-human animals.

physiology↗

A whole-brain analysis of functional connectivity and immediate early gene expression revealed functional network shifts after operant learning

Previous studies of operant learning have addressed neuronal activities and network changes in specific brain areas, such as the striatum, sensorimotor cortex, prefrontal/orbitofrontal cortices, and hippocampus. However, how changes in the whole-brain network are caused by cellular-level changes remains unclear. We combine resting-state functional magnetic resonance imaging (rsfMRI) and whole-brain immunohistochemical analysis of early growth response 1 (EGR1), a marker of neural plasticity, to elucidate the spatiotemporal functional network changes and underlying cellular processes during operant learning. We used an 11.7 Tesla scanner and whole-brain immunohistochemical analysis of EGR1 in mice during the early and late stages of operant learning. In the operant training, mice received a reward when they pressed the left and right buttons alternately and were punished with a bright light when they made a mistake. Control mice spent the same time and received the same amount of reward in the same operant box. A group of mice (n = 22) underwent the first rsfMRI before behavioral sessions, the second after 3 days of sessions (early stage), and the third after 21 days of sessions (late stage). Another group of mice (n = 40) was subjected to histological analysis 15 min after the early or late stages of behavioral sessions. After the early stage of training, functional connectivity was increased between the limbic areas and thalamus or auditory cortex, and the correlations of the number of EGR1-immunopositive cells between the limbic area and auditory cortex were also increased. After the late stage of training, the increases in functional connectivity and correlations of EGR1-immunopositive cells primarily occurred between the motor cortex, somatosensory cortex, and striatum. The subcortical networks centered around the limbic areas that emerged in the early stage have been implicated in rewards, pleasures, and fears. The connectivity between the motor cortex, somatosensory cortex, and striatum that consolidated in the late stage have been implicated in motor learning. Our multimodal longitudinal study successfully revealed the temporal shifts of brain regions involved in behavioral learning together with the underlying cellular-level plasticity between these regions for the first time. Our study represents a first step toward establishing a new experimental paradigm that combines rsfMRI and immunohistochemistry for linking macroscopic and microscopic mechanisms of learning.

neuroscience↗

Neuronal representation of a working memory-based decision strategy in the motor and prefrontal cortico-basal ganglia loops

While animal and human decision strategies are typically explained by model-free and model-based reinforcement learning, their choice sequences often follow simple procedures based on working memory of past actions and rewards. Here we address how working memory-based choice strategies, such as win-stay-lose-switch (WSLS), are represented in the prefrontal and motor cortico-basal ganglia loops by simultaneous recording of neuronal activities in the dorsomedial striatum (DMS), the dorsolateral striatum (DLS), the medial prefrontal cortex (mPFC), and the primary motor cortex (M1). In order to compare neuronal representations when rats employ working memory-based strategies, we developed a new task paradigm, a continuous/intermittent choice task, consisting of choice and no-choice trials. While the continuous condition (CC) consisted of only choice trials, in the intermittent condition (IC), a no-choice trial was inserted after each choice trial to disrupt working memory of the previous choice and reward. Behaviors in CC showed high proportions of win-stay and lose-switch choices, which could be regarded as "a noisy WSLS strategy." Poisson regression of neural spikes revealed encoding specifically in CC of the previous action and reward before action choice and prospective coding of WSLS action during action execution. A striking finding was that the DLS and M1 in the motor cortico-basal ganglia loop carry substantial WM information about previous choices, rewards, and their interactions, in addition to current action coding. Significance StatementWorking memory-based decision strategies, such as win-stay-lose-switch (WSLS), are widely observed in humans and animals. To address neuronal bases of these strategies, we recorded neuronal activities of rat prefrontal and motor cortico-basal ganglia loops during continuous/intermittent choice tasks. The rat choice strategy was a noisy WSLS in the continuous choice condition, whereas non-WSLS was selected in the intermittent choice condition. In the continuous choice condition, the primary motor cortex and the dorsolateral striatum in the motor loop more strongly conveyed information about previous choices, rewards, and their interactions than the medial prefrontal cortex and the dorsomedial striatum in the prefrontal loop. These results demonstrate that the motor cortico-basal ganglia loop contributes to working memory-based decision strategies.

neuroscience↗

Optogenetic activation of dorsal raphe serotonin neurons induces a brain-wide response in reward network

Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear. Here we measured brain-wide responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7T scanner and a cryoprobe. Transient activation of DRN serotonin neurons caused brain-wide activation, including the medial prefrontal cortex, the striatum, and the ventral tegmental area. The same stimulation under anesthesia with isoflurane decreased brain-wide activation, including the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 receptors. Together, these results provide insight into the DR serotonergic system, which is consistent with recent discoveries of its functions in adaptive behaviors.

neuroscience↗

The Brain/MINDS Marmoset Connectivity Atlas: Exploring bidirectional tracing and tractography in the same stereotaxic space

We report on the implementation and features of the Brain/MINDS Marmoset Connectivity Atlas, BMCA, a new resource that provides access to anterograde neuronal tracer data in the prefrontal cortex of a marmoset brain. Neuronal tracers combined with fluorescence microscopy are a key technology for the systematic mapping of structural brain connectivity. We selected the prefrontal cortex for mapping due to its important role in higher brain functions. This work introduces the BMCA standard image preprocessing pipeline and tools for exploring and reviewing the data. We developed the BMCA-Explorer, which is an online image viewer designed for data exploration. Unlike other existing image explorers, it visualizes the data of different individuals in a common reference space at an unprecedented high resolution, facilitating comparative studies. To foster the integration with other marmoset brain image databases and cross-species comparisons, we added fiber tractography data from diffusion MRI, retrograde neural tracer data from the Marmoset Brain Connectivity Atlas project, and tools to map image data between marmoset and the human brain image space. This version of BMCA allows direct comparison between the results of 52 anterograde and 164 retrograde tracer injections in the cortex of the marmoset.

neuroscience↗

Automated segmentation of insect anatomy from micro-CT images using deep learning

Three-dimensional (3D) imaging, such as micro-computed tomography (micro-CT), is increasingly being used by organismal biologists for precise and comprehensive anatomical characterization. However, the segmentation of anatomical structures remains a bottleneck in research, often requiring tedious manual work. Here, we propose a pipeline for the fully-automated segmentation of anatomical structures in micro-CT images utilizing state-of-the-art deep learning methods, selecting the ant brain as a test case. We implemented the U-Net architecture for 2D image segmentation for our convolutional neural network (CNN), combined with pixel-island detection. For training and validation of the network, we assembled a dataset of semi-manually segmented brain images of 94 ant species. The trained network predicted the brain area in ant images fast and accurately; its performance tested on validation sets showed good agreement between the prediction and the target, scoring 80% Intersection over Union (IoU) and 90% Dice Coefficient (F1) accuracy. While manual segmentation usually takes many hours for each brain, the trained network takes only a few minutes. Furthermore, our network is generalizable for segmenting the whole neural system in full-body scans, and works in tests on distantly related and morphologically divergent insects (e.g., fruit flies). The latter suggest that methods like the one presented here generally apply across diverse taxa. Our method makes the construction of segmented maps and the morphological quantification of different species more efficient and scalable to large datasets, a step toward a big data approach to organismal anatomy.

evolutionary biology↗