Biology subjects

Aoki, R.

Publications and source records attributed to Aoki, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Spatiotemporal spinal integration of descending and spinal volleys in spinal motor circuits revealed by compound motor evoked potentials

Descending corticospinal and afferent pathways underlying spinally evoked motor potential both contribute to motor output, yet how their interaction at the spinal and peripheral levels is organized spatially within a muscle remains unclear. This study investigated the spatiotemporal characteristics of descending modulation of spinally evoked motor potentials by combining subthreshold transcranial magnetic stimulation (TMS) with transcutaneous spinal cord stimulation (tSCS). In Experiment 1, spinally evoked motor potentials were recorded from multiple lower-limb muscles at various interstimulus intervals (ISIs) defined relative to central conduction time (CCT). Subthreshold TMS facilitated spinally evoked motor potentials from CCT onward across all recorded muscles, with additional bilateral facilitation observed at longer ISIs. In Experiment 2, high-density surface electromyography (HDsEMG) revealed distinct intramuscular activation patterns in the tibialis anterior. The center of gravity (CoG) of TMS-induced motor evoked potentials was located more proximally than that of spinally evoked motor potentials. Notably, the CoG of facilitation maps was shifted further proximally than that of both single-stimulus responses. These findings suggest that descending and afferent inputs preferentially recruit partially distinct motoneuron pools within the same muscle. The proximal bias of facilitation indicates recruitment of additional motoneurons rather than uniform amplification of existing activity. Together, these results demonstrate that the interaction between descending and afferent inputs is both timing-dependent and spatially non-uniform, providing new insight into sensorimotor integration in the human lower limb.

neuroscience↗

bioRxiv2026

Subsecond whole-brain neural dynamics identified by hidden Markov modeling reflect value-based decision making in humans

Value-based decision making emerges from coordinated neural dynamics across distributed brain networks. Recent studies using noninvasive whole-brain measurements in humans have highlighted the importance of neural activity in the 2-10 Hz frequency band for value-based decision making. Using magnetoencephalography and hidden Markov model (HMM) analysis, we examined whether and how whole-brain neural dynamics in this frequency band, evolving on a timescale of a few hundred milliseconds, reflect value-based decision processes. Thirty-five healthy adults (females and males) made binary choices between risky and sure options. Trial-wise subjective values were estimated using behavioral economic modeling based on prospect theory. We found that HMM-derived trial-by-trial whole-brain neural dynamics (defined by 2-10 Hz amplitude envelopes in distributed brain regions and their interregional coupling) were associated with the subjective values of choice options in a manner distinct from simple perceptual- or motor-evoked activity. Notably, these trial-by-trial whole-brain dynamics covaried with the difference in subjective values between the chosen and unchosen options when the neural data were time-locked to participants responses, but not when time-locked to option onset. These findings revealed a crucial link between subsecond whole-brain neural dynamics and trial-by-trial decision variables, providing insights into how value-based decision processes unfold over time in the human brain.

neuroscience↗

bioRxiv2026

Preserved Intrinsic Neural Timescale Organization with Hierarchical Variation in Autism Spectrum Disorder

Intrinsic neural timescales (INTs) index the temporal decay of neural activity and form a cortical hierarchy from fast sensorimotor to slow transmodal regions. Altered INTs have been reported in autism spectrum disorder (ASD), but it remains unclear whether the hierarchical organization is preserved and how individual variability along this hierarchy relates to sensory traits. Using resting-state fMRI from 182 participants (67 ASD, 115 typically developed controls (TDC)), we estimated INT at each cortical vertex from the autocorrelation half-life and averaged these values across four five-minute runs per participant. Vertex-wise INTs were then averaged within predefined cortical parcels and large-scale functional networks for subsequent analyses. The cortical INT hierarchy was preserved in ASD, showing comparable sensorimotor-to-transmodal hierarchy in both groups. However, regions operating at longer timescales showed prolonged INTs in ASD, and such tendency increased systematically along the hierarchy. No vertex, parcel, or network survived correction of multiple comparisons, indicating that observed alterations followed a distributed hierarchical trend rather than a focal pattern. To disentangle group-level differences from inter-individual variability, we next modeled each participants parcel-wise INT profile relative to a TDC-derived group-averaged template. At the individual level, decomposition of INT profiles revealed that global shifts and hierarchical scaling primarily reflected demographic variation (plimarily sex) rather than diagnostic group membership. After accounting for these components, residual deviations from theTDC-derived cortical INT hierarchy showed a modest association with sensory traits characterized by reduced sensory registration. Together, these findings indicate that while the large-scale hierarchical organization of cortical temporal dynamics is largely preserved in ASD, individual-specific deviations from this hierarchy may contribute to variability in sensory experience beyond group-level differences. HighlightsO_LIAcross both autism spectrum disorder (ASD) and typically developed controls (TDC), intrinsic neural timescales (INTs) followed the established sensory cortical hierarchy and showed a negative association with cortical microstructural markers (myelin content and neurite density index), with no group difference in hierarchical slope. C_LIO_LIAt the whole-brain level, the hierarchical organization of INTs was preserved across ASD and TDC, although regions operating at longer timescales exhibited relatively greater extension in ASD. C_LIO_LIGlobal shifts and hierarchical scaling, describing individual positioning within the INT-based cortical hierarchy, were more strongly associated with demographic variation (primarily sex) than with diagnosis. C_LIO_LIAfter accounting for these global and hierarchical components, residual deviations from the INT-based cortical hierarchy were modestly associated with sensory traits characterized by reduced sensory registration. C_LI

neuroscience↗

bioRxiv2025

Psychological scales in the brain: Trait-linked questionnaire items evoke similar neural patterns in the mPFC

Self-report questionnaires are widely used across psychology and related disciplines, yet the cognitive and neural processes underlying how individuals generate responses to such items remain poorly understood. Here, we investigated whether items from the same psychological scale evoke similar neural activation patterns in the medial prefrontal cortex (mPFC), a region consistently implicated in self-referential processing. While undergoing functional magnetic resonance imaging (fMRI), participants completed a self-reference task in which they judged how well 72 personality-related questionnaire items (e.g., from the Big Five, emotion regulation, and well-being scales) described themselves. Using representational similarity analysis (RSA), we found that items from the same scale elicited more similar multivoxel activation patterns in the mPFC compared to items from different scales. This effect was specific to the self-reference task and was not observed during a semantic judgment control task using the same items. Furthermore, the mPFC encoded not only categorical scale membership but also graded psychological similarity among scales, as reflected in inter-scale behavioral correlations. Importantly, these effects remained significant even after controlling for sentence-level semantic similarity using multiple regression RSA, indicating that the observed neural structure reflects psychological rather than linguistic similarity. These findings suggest that the mPFC integrates internally constructed evidence in a construct-sensitive manner during self-report, and they open new avenues for linking psychological assessment with neural representation. We discuss the implications for understanding self-report as a cognitive process and for future work on neuroimaging-informed scale validation. Significance statementSelf-report questionnaires are widely used across psychology, medicine, and public policy to assess thoughts, feelings, and personality traits. However, little is known about how the brain generates these responses. Using fMRI and a multivariate analysis approach, we found that questionnaire items measuring the same psychological construct evoked similar activity patterns in the medial prefrontal cortex--a region involved in self-reflection. This effect was specific to self-referential judgments and remained significant even after controlling for sentence-level semantic similarity, suggesting that the brain organizes information according to underlying psychological traits rather than linguistic features. These findings offer new insights into how self-report operates at the neural level and may inform future approaches to scale development.

neuroscience↗

bioRxiv2025

A multimodal dataset linking wide-field calcium imaging to behavior changes in mice during an operant lever-pull task

The BraiDyn-BC (Brain Dynamics underlying emergence of Behavioral Change) Database offers an extensive, multimodal dataset that links wide-field calcium imaging of the mouse neocortex to comprehensive behavioral measurements during a behavioral task. As one of the contents in this database, we newly provide a dataset that includes 15 sessions spanning two weeks of motor skill learning, in which 25 mice were trained to pull a lever to obtain water rewards. Simultaneous high-speed videography captures body, facial, and eye movements, and environmental parameters are monitored. The dataset also features resting-state cortical activity and sensory-evoked responses, enhancing its utility for both learning-related and sensory-driven neural dynamics studies. Data are formatted in accordance with the Neurodata Without Borders (NWB) standard, ensuring compatibility with existing analysis tools and adherence to the FAIR principles. This resource enables in-depth investigations into the neural mechanisms underlying behavior and learning. The platform encourages collaborative research, supporting the exploration of rapid within-session learning effects, long-term behavioral adaptations, and neural circuit dynamics.

neuroscience↗

bioRxiv2024

Decomposing Cognitive Processes in the mPFC During Self-Thinking

Past cognitive neuroscience research has demonstrated that thinking about both the self and other activate the medial prefrontal cortex (mPFC), a central hub of the default mode network. The mPFC is also implicated in other cognitive processes, such as introspection and autobiographical memory, rendering elusive its exact role during thinking about the self. Specifically, it is unclear whether the same cognitive process explains the common mPFC involvement or distinct processes are responsible for the mPFC activation overlap. In this preregistered functional magnetic resonance imaging study, we investigated whether and to what extent mPFC activation patterns during self-reference judgment could be explained by activation patterns during the tasks of other-reference judgment, introspection, and autobiographical memory. Multi-voxel pattern analysis showed that only in the mPFC were neural responses both concurrently different and similar across tasks. Furthermore, multiple regression and variance partitioning analyses indicated that each task (i.e., other-reference, introspection, memory) uniquely and jointly explained significant variance in mPFC activation during self-reference. These findings suggest that the self-reference task involves multiple cognitive processes shared with other tasks, and the mPFC is the unique place where necessary information is gathered and integrated for judgments based on internally constructed representations.

neuroscience↗

bioRxiv2024

Optimization of microRNA Target Sequence Arrangement in AAV Vectors Dramatically Enhances Specificity and Efficiency of Transgene Expression in Cortical Microglia

Microglia play a critical role in diseases such as Alzheimers and stroke, making them a significant target for therapeutic intervention. However, due to their immune functions in detecting and combating viral invasion, efficient gene delivery to microglia remains challenging. We achieved specific and efficient gene delivery to microglia using an adeno- associated virus (AAV) vector designed for this purpose. This microglia-targeting AAV vector includes the mouse microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (mIba1) promoter, green fluorescent protein (GFP), microRNA target sequences (miR.Ts), woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), and polyadenylation (polyA) signal, positioned between inverted terminal repeats. When miR.Ts were placed downstream of WPRE (between WPRE and polyA), gene expression occurred not only in microglia but also in a substantial number of neurons. However, when miR.Ts were positioned upstream of WPRE (between GFP and WPRE) or on both sides of WPRE, neuronal expression was significantly suppressed, resulting in selective GFP expression in microglia. Notably, positioning miR.Ts on both sides of WPRE achieved over 90% specificity and more than 60% efficiency in transgene expression in microglia three weeks after viral administration. This vector also enabled GCaMP expression in microglia, facilitating real-time monitoring of calcium dynamics and microglial process activity in the cortex. Additionally, intravenous administration of this vector with the blood-brain barrier-penetrant AAV-9P31 capsid variant resulted in extensive GFP expression selectively in microglia throughout the brain. These findings establish this AAV vector system as a robust tool for long-term, specific, and efficient gene expression in microglia.

neuroscience↗

bioRxiv2023

Transgenic tools targeting striatal and pallidal subpopulations revealed evolutionary conservation and specialization of the cortico-basal ganglia circuit in zebrafish

The cortico-basal ganglia circuit mediates decision-making. Here, we generated transgenic tools for adult zebrafish targeting specific subpopulations of the components of this circuit and utilized them to identify evolutionary homologs of the mammalian direct- and indirect-pathway striatal neurons which respectively project to the homologs of the internal and external segment of the globus pallidus (dEN and Vl) as in mammals. Unlike in mammals, the Vl mainly projected to the dEN directly, not by way of the subthalamic nucleus. Further single-cell RNA sequencing analysis revealed two pallidal output pathways: a major shortcut pathway directly connecting the dEN with the pallium and the evolutionarily conserved closed loop by way of the thalamus. Our resources and circuit map provide the common basis for the functional study of the basal ganglia in a small and optically tractable zebrafish brain for the comprehensive mechanistic understanding of the cortico-basal ganglia circuit.

neuroscience↗

bioRxiv2023

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; all P<0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

neuroscience↗

bioRxiv2022

Neural Representation of The Self

Knowledge about ones personality, the self-concept, shapes human experience. Social cognitive neuroscience has made strides addressing the question of where and how the self is represented in the brain. The answer, however, remains elusive. We conducted two functional magnetic resonance imaging experiments (with the second being preregistered) employing a self-reference task with a broad range of attributes and carrying out a searchlight representational similarity analysis. The importance of attributes to self-identity was represented in the medial prefrontal cortex (mPFC), whereas mPFC activation was unrelated both to self-descriptiveness of attributes (Experiments 1-2) and importance of attributes to a friends self-identity (Experiment 2). Our research provides a comprehensive answer to the abovementioned question: The self-concept is conceptualized in terms of self-importance and represented in the mPFC.

neuroscience↗

bioRxiv2022

Efficient coding of natural images in the mouse visual cortex

How communication between neurons gives rise to natural vision remains a matter of intense investigation. The mid-level visual areas along the ventral stream, as studies in primates have shown, are selective to a common class of natural images--textures--but a circuit-level understanding of this selectivity and its link to perception remain unclear. We addressed these questions in mice, first showing that they can perceptually discriminate between texture types and statistically simpler spectrally matched stimuli. Then, at the neural level, we found that the secondary visual area (LM), more than the primary one (V1), was selective for the higher-order statistics of textures, both at the mesoscopic and single-cell levels. At the circuit level, textures were encoded in neural activity subspaces whose relative distances correlated with the statistical complexity of the images and with the mices ability to discriminate between them. These dependencies were more significant in LM, in which the texture-related subspaces were smaller and closer to each other, enabling better stimulus decoding in this area. Together, our results demonstrate texture vision in mice, finding a linking framework between stimulus statistics, neural representations, and perceptual sensitivity--a distinct hallmark of efficient coding computations.

neuroscience↗

bioRxiv2021

Executive control by fronto-parietal activity explains counterintuitive decision behavior in complex value-based decision-making

In real life, humans make decisions by taking into account multiple independent factors, such as delay and probability. Cognitive psychology suggests that cognitive control mechanisms play a key role when facing such complex task conditions. However, in value-based decision-making, it still remains unclear to what extent cognitive control mechanisms become essential when the task condition is complex. In this study, we investigated decision-making behaviors and underlying neural mechanisms using a multifactor gambling task where participants simultaneously considered probability and delay. Decision-making behavior in the multifactor task was modulated by both probability and delay. The behavioral effect of probability was stronger than delay, consistent with previous studies. Furthermore, in a subset of conditions that recruited fronto-parietal activations, reaction times were paradoxically elongated despite lower probabilistic uncertainty. Notably, such a reaction time elongation did not occur in control tasks involving single factors. Meta-analysis of brain activations suggested an association between the paradoxical increase of reaction time and strategy switching. Together, these results suggest a novel aspect of complex value-based decision-makings that is strongly influenced by fronto-parietal cognitive control. Highlights* A value-based decision task with concurrent delay and probabilistic uncertainty * Stronger behavioral effect of probability than delay * Paradoxically long reaction time despite low probabilistic uncertainty * The task activated fronto-parietal cognitive control network * Reaction time elongation coincided with activation similar to strategy switching

neuroscience↗

bioRxiv2021

Effects of upgrading acquisition-techniques and harmonization methods: A multi-modal MRI study with implications for longitudinal designs

A downside of upgrading MRI acquisition sequences is the discontinuity of technological homogeneity of the MRI data. It hampers combining new and old datasets, especially in a longitudinal design. Characterizing upgrading effects on multiple brain parameters and examining the efficacy of harmonization methods are essential. This study investigated the upgrading effects on three structural parameters, including cortical thickness (CT), surface area (SA), cortical volume (CV), and resting-state functional connectivity (rs-FC) collected from 64 healthy volunteers. We used two evaluation metrics, Cohens d and classification accuracy, to quantify the effects. In classification analyses, we built classifiers for differentiating the protocols from brain parameters. We investigated the efficacy of three harmonization methods, including traveling subject (TS), TS-ComBat, and ComBat methods, and the sufficient number of participants for eliminating the effects on the evaluation metrics. Finally, we performed age prediction as an example to confirm that harmonization methods retained biological information. The results without harmonization methods revealed small to large mean Cohens d values on brain parameters (CT:0.85, SA:0.66, CV:0.68, and rs-FC:0.24) with better classification accuracy (>92% accuracy). With harmonization methods, Cohens d values approached zero. Classification performance reached the chance level with TS-based techniques when data from less than 26 participants were used for estimating the effects, while the Combat method required more participants. Furthermore, harmonization methods improved age prediction performance, except for the ComBat method. These results suggest that acquiring TS data is essential to preserve the continuity of MRI data.

neuroscience↗

bioRxiv2021

Distributed context-dependent choice information in mouse dorsal-parietal cortex

Choice information appears in the brain as distributed signals with top-down and bottom-up components that together support decision-making computations. In sensory and associative cortical regions, the presence of choice signals, their strength, and area specificity are known to be elusive and changeable, limiting a cohesive understanding of their computational significance. In this study, examining the mesoscale activity in mouse posterior cortex during a complex visual discrimination task, we found that broadly distributed choice signals defined a decision variable in a low-dimensional embedding space of multi-area activations, particularly along the ventral visual stream. The subspace they defined was near-orthogonal to concurrently represented sensory and motor-related activations, and it was modulated by task difficulty and contextually by the animals attention state. To mechanistically relate choice representations to decision-making computations, we trained recurrent neural networks with the animals choices and found an equivalent decision variable whose context-dependent dynamics agreed with that of the neural data. In conclusion, our results demonstrated an independent decision variable broadly represented in the posterior cortex, controlled by task features and cognitive demands. Its dynamics reflected decision computations, possibly linked to context-dependent feedback signals used for probabilistic-inference computations in variable animal-environment interactions.

neuroscience↗

bioRxiv2020

Mice can learn a stimulus-invariant orientation discrimination task

Understanding how the brain computes choice from sensory information is a central question in perceptual decision-making research. From a behavioral perspective, paradigms suitable to study perceptual decision-making condition choice on invariant properties of the stimuli, thus decoupling stimulus-specific information from decision-related variables. From a neural perspective, powerful tools for the dissection of brain circuits are needed, which suggests the mouse as a suitable animal model. However, whether and how mice can perform an invariant visual discrimination task has not yet been fully established. Here, we show that mice can solve a complex orientation discrimination task where the choices are decoupled from the orientation of individual stimuli. Moreover, we demonstrate a discrimination acuity of at least 6{degrees}, challenging the common belief that mice are poor visual discriminators. We reached these conclusions by introducing a novel probabilistic choice model that explained behavioral strategies in (n = 40) mice and identified unreported dimensions of variation associated with the circularity of the stimulus space. Furthermore, the model showed a dependence of history biases on task engagement, demonstrating behavioral sensitivity to the availability of cognitive resources. In conclusion, our results reveal that mice are capable of decoupling decision-relevant information from stimulus-specific information, thus demonstrating they are a useful animal model for studying neural representation of abstract learned categories in perceptual decision-making research.

neuroscience↗

bioRxiv2020

Flexible decision under ambiguous cues reverses neural signaling from occipitotemporal to prefrontal cortex

Adaptation to changing environments involves the appropriate extraction of environmental information to achieve a behavioral goal. It remains unclear how behavioral flexibility is guided under situations where the relevant behavior is ambiguous. Using functional brain mapping of machine-learning decoders and directional functional connectivity, we show that brain-wide reversible neural signaling underpins task encoding and behavioral flexibility in ambiguously changing environments. When relevant behavior is cued ambiguously during behavioral shifting, neural coding is attenuated in distributed cortical regions, but top-down signals from the prefrontal cortex complement the coding. When behavioral shifting is cued more explicitly, modality-specialized occipitotemporal regions implement distinct neural coding about relevant behavior, and bottom-up signals from the occipitotemporal region to the prefrontal cortex supplement the behavioral shift. These results suggest that our adaptation to an ever-changing world is orchestrated by the alternation of top-down and bottom-up signaling in the fronto-occipitotemporal circuit depending on the availability of environmental information.

neuroscience↗

bioRxiv2020

AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication

Autism susceptibility candidate 2 (AUTS2), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development. Auts2 conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a. Auts2 cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses, and restriction of parallel fiber synapse numbers. Auts2 cKO mice exhibited behavioral impairments in motor learning and vocal communications. Because Cacna1a is known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment of AUTS2 may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs.

neuroscience↗

bioRxiv2019

Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis

The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases (IBDs); however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin not only establishes a first-line barrier against pathogens, but also serves as a niche for microbial growth. We hypothesized that dysbiosis may cause abnormal mucin utilization and microbial metabolic dysfunction. To test this hypothesis, we analyzed short-chain fatty acids (SCFAs) and mucin components in the stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohns disease (CD) patients from Japan. The levels of n-butyrate were significantly lower in the stools of both the CD and UC patients than in those of the healthy subjects. Correlation analysis identified 7 bacterial species positively correlated with n-butyrate levels, among which the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans act as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in the colonic lamina propria. Importantly, the availability of mucin-associated O-glycans to the microbiota was significantly reduced in n-butyrate-deficient UC patients. Taken together, our findings highlight the biological significance of the symbiosynthesis pathway in the production of n-butyrate, which maintains gut immune homeostasis.

microbiology↗