Biology subjects

Takeda, M.

Publications and source records attributed to Takeda, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Beyond Temporary Scaffolding: Persistent Hippocampal Engagement and Brain-Wide Network Reorganization in Remote Memory Consolidation

The standard model of memory consolidation posits a temporary role for the hippocampus. We challenge this view by combining a novel face-name associative memory task with cross-modal decoding of fMRI data. We demonstrate that the hippocampus remains persistently engaged in representing both recent and remote memories, with distinct subregional contributions: recent memories were represented in the right posterior hippocampus, whereas remote memories additionally recruited the left anterior hippocampus. This sustained hippocampal involvement occurred alongside a large-scale network reorganization. Remote memory retrieval was accompanied by increased global connectivity among semantic regions, yet the hippocampus itself did not emerge as a major hub. Instead, network hubs shifted from the medial prefrontal cortex (mPFC) for recent memories to the mPFC and bilateral inferior parietal lobule for remote memories. These findings reveal a dynamic process in which the hippocampus preserves long-lasting representational functions while the broader memory network undergoes extensive reorganization.

neuroscience↗

bioRxiv2026

Asynchronous cortical recovery from sleep inertia: region- and frequency-specific dynamics following deep NREM sleep

Sleep inertia (SI) is a transient state of impaired alertness and cognition after awakening, typically exacerbated by prior deep sleep. Despite its prevalence, the fine-grained temporal dynamics of brain activity during this transition remains poorly understood. We employed trial-by-trial behavioral assessment (20-second resolution) to map the recovery trajectories of 44 participants following awakenings from either shallow (N1/N2) or deep (N3) NREM sleep. We found that awakening from deep NREM sleep resulted in a significantly slower return to baseline working-memory performance. This behavioral deficit was mirrored by specific EEG signatures: frontal low-frequency activity (delta/theta) returned to baseline levels within minutes, whereas posterior high-frequency activity (alpha/beta) remained altered for a prolonged period. These findings reveal that the human brain reboots asynchronously following deep NREM sleep, with a "frontal-first, posterior-last" gradient that dictates the time course of behavioral restoration.

neuroscience↗

bioRxiv2026

Cell-intrinsic compliance mechanism enables release of tensile stress to prevent tissue rupture

Contractile forces are necessary to sculpt tissue structures and organ shapes during morphogenesis. In the early embryo, this presents an engineering challenge as the deforming tissue can be relatively large, while the forces thus generated might be poorly compartmentalized, generating tensile stresses that can cause damage if unmitigated. Here we show that during Drosophila gastrulation, the squamous morphogenesis of the extraembryonic amnioserosa functions mechanically to release tensile stresses yielded from the neighboring ectodermal convergent-extension and mesodermal invagination. Amnioserosa master regulator Zen transcriptionally silences shroom to endow it with low junctional actomyosin stresses, thereby ensuring high mechanical compliance. Loss of Zen, or targeted ectopic expression of Shroom in the amnioserosa using a novel optogenetic Gal4 system, leads to increased junctional myosin, thereby causing load-dependent tissue ruptures. Our data establish a previously unknown function for the Drosophila extraembryonic tissue, whereby cell-intrinsic mechanical compliance prevents tissue rupture to mitigate inter-tissue mechanical conflicts.

developmental biology↗

bioRxiv2026

Deep-learning-based fMRI decoding of real-world size for hand-held objects

Real-world object size is a fundamental dimension of visual cognition, supporting effective interaction with the environment and object manipulation. However, neural mechanisms encoding size have largely been inferred from extreme size comparisons, leaving the neural representation of subtle size differences within a manipulable, "hand-scale" range poorly understood. Here, we applied a three-dimensional deep neural network (3D DNN) to decode real-world size from whole-brain fMRI data (N = 50) using objects that all fall within a graspable range. The 3D DNN successfully decoded subtle size differences, achieving predictive accuracies comparable to multivariate pattern analysis. Crucially, Guided Gradient-weighted Class Activation Mapping (Guided Grad-CAM) revealed that discriminative size information was not confined to the ventral occipito-temporal cortex but extended to a distributed network. Notably, these regions spatially overlap with the specific brain areas implicated in size-perception distortions following brain damage. Our findings suggest that the brain represents subtle variations in object size through a non-linear, distributed network that transcends the traditional visual hierarchy. Specifically, this system likely orchestrates the integration of visual properties with semantic scaling and the multimodal convergence of vision, space, and memory.

neuroscience↗

bioRxiv2025

Evolutionary and structural basis of SLAM utilization in morbilliviruses - Its implications for host range and cross-species transmission

Morbilliviruses, including measles virus (MV), canine distemper virus (CDV), and cetacean morbillivirus, pose a significant threat to humans and animals. While the host range of morbilliviruses is generally well-defined, severe cross-species transmission events also have been reported. Their entry into immune cells, the primary targets of morbilliviruses, relies on the signaling lymphocytic activation molecule (SLAM), a receptor whose species-specific variations influence viral host range. However, the extent to which SLAM diversity is a barrier to cross-species transmission remains poorly understood. In this study, we systematically investigated SLAM-mediated host specificity. We found that most morbilliviruses efficiently utilize SLAM from multiple host species, except for human SLAM. Among the morbilliviruses tested, only MV efficiently utilized human SLAM. Bats are natural reservoirs for many zoonotic viruses. Recent discoveries of novel morbilliviruses in bats provide new insights into morbillivirus evolution. Bats may have played a significant role in morbillivirus evolution because bat (Myotis) SLAM also functioned as an efficient receptor for multiple morbilliviruses. Unlike other morbilliviruses, MV utilized Myotis bat SLAM inefficiently. We conducted an MV adaptation experiment with Myotis bat SLAM to better understand SLAM recognition by morbilliviruses. MV readily adapted to utilize Myotis bat SLAM by acquiring a single N187Y mutation in its hemagglutinin protein, and computational structural modeling and fragment molecular orbital calculations with molecular dynamics simulations revealed key interaction changes that facilitated MVs adaptation to Myotis bat SLAM. These findings highlight the adaptability of morbilliviruses in utilizing diverse animal SLAMs. Notably, hypothetical ancestral SLAMs reconstructed in this study acted as universal receptors for all morbilliviruses. These results reinforced that morbillivirus receptor usage is primarily supported by evolutionarily conserved structural features of SLAM, highlighting a molecular basis that enables morbilliviruses to rapidly adapt to diverse animal SLAMs. Author SummaryOur study explores how viruses in the genus morbillivirus, such as measles virus, canine distemper virus, and rinderpest virus, which are notorious for deadly outbreaks in humans and animals, can jump between species. The host range of morbilliviruses is significantly influenced by a receptor molecule on cell surfaces known as the signaling lymphocytic activating molecule (SLAM). By examining SLAMs from various animals, including humans, dolphins, dogs, seals, and bats, we observed how these viruses can infect or adapt to infect different hosts. We found that in some cases slight differences in SLAM may act as initial barriers to cross-species transmission. However, these viruses rapidly overcome such barriers, showing a remarkable ability to adapt. Our research highlights the importance of monitoring these viruses to predict and prevent potential cross-species infections, which is crucial for protecting public health and animal welfare over time.

microbiology↗

bioRxiv2024

Therapeutic targeting of Syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers

The therapeutic benefit of recently developed mutant KRAS (mKRAS) inhibitors has been limited by the rapid onset of resistance. Here, we aimed to delineate the mechanisms underlying acquired resistance to mKRAS inhibition and identify actionable targets for overcoming this clinical challenge. Previously, we identified Syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by mKRAS. By leveraging both pancreatic and colorectal cancer models, we found that surface SDC1 expression was initially diminished upon mKRAS inhibition, but recovered in tumor cells that bypass mKRAS dependency. Functional studies showed that these tumors depended on SDC1 for survival, further establishing SDC1 as a driver for the acquired resistance to mKRAS inhibition. Mechanistically, we revealed that the YAP1-SDC1 axis was the major driving force for bypassing mKRAS dependency to sustain nutrient salvage machinery and tumor maintenance. Specifically, YAP1 activation mediated the recovery of SDC1 localization on cell surface that sustained macropinocytosis and enhanced the activation of multiple RTKs, promoting resistance to KRAS-targeted therapy. Overall, our study has provided the rationale for targeting the YAP-SDC1 axis to overcome resistance to mKRAS inhibition, thereby revealing new therapeutic opportunities for improving the clinical outcome of patients with KRAS-mutated cancers.

cancer biology↗

bioRxiv2024

A novel genetic mouse model of fatal aortic dissection reveals massive inflammatory cell infiltration in the thoracic aorta

BackgroundAortic dissection (AD) is the separation of medial layers of the aorta and is a major cause of death in patients with connective tissue disorders such as Marfan syndrome. However, molecular triggers instigating AD, its temporospatial progression, and how vascular cells in each vessel layer interact and participate in the pathological process remain incompletely understood. To unravel the underlying molecular mechanism of AD, we generated a spontaneous AD mouse model. MethodsWe incorporated a novel missense variant (p.G234D) in FBN1, the gene for fibrillin-1, identified in a non-syndromic familial AD patient into mice using CRISPR/Cas9 system. We performed histopathological analyses of the aortic lesions by histology, immunofluorescence staining, electron microscopy, synchrotron-based imaging and single-cell (sc)RNA-sequencing. Biochemical analysis was performed to examine the binding capacity of mutant human FBN1G234D protein to latent Tgf{beta} binding proteins (LTBPs), and signaling pathways in the mutant aortic wall were examined by western blot analysis. Results50% of the Fbn1G234D/G234D mutant mice died within 5 weeks of age from multiple intimomedial tears that expanded longitudinally and progressed to aortic rupture accompanied by massive immune cell infiltration. scRNA-sequencing, validated by immunostaining, revealed a significant increase in MHC class II-positive pro-inflammatory macrophages and monocytes at the site of intima tears with upregulation of MMP2/9 and marked disruption of elastic lamina. Subendothelial matrices, such as type IV collagen and laminin, expanded into the medial layer, where fibronectin expression was highly upregulated. Fbn1G234D/G234D endothelial cells exhibited altered mechanosensing with loss of parallel alignment to blood flow and upregulation of VCAM-1 and ICAM-1, all of which likely contributed to the infiltration of immune cells. Biochemically, FBN1G234D lost the ability to bind to latent TGF{beta} binding protein (LTBP)-1, -2, and -4, resulting in the downregulation of TGF{beta} signaling in the aortic wall. ConclusionsWe show that dynamic interactions involving endothelial cells (ECs) and macrophages/monocytes in the intima, where the ECM microenvironment is altered with the reduced TGF{beta} signaling, contributes to the initiation of AD. Our novel AD mouse model provides a unique opportunity to identify target molecules involved in the intimomedial tears that can be utilized for development of therapeutic strategies.

pathology↗

bioRxiv2024

Neural signatures of human psychological resilience driven by acute stress

Neurophysiological mechanisms underlying psychological resilience, the ability to overcome adversity1,2, have been extensively studied in animals. However, in comparison with animals, human resilience is unique in that it is underpinned by higher cognitive functions, such as self-confidence and a positive attitude to challenges3,4. Given these discrepancies, the neurophysiological mechanisms underlying human resilience remain unclear. To address this issue, we recorded multimodal responses after acute stress exposure over 1.5 hours using functional brain imaging and peripheral physiological measurements. Here, we showed that the degree of individual resilience is indexed by multiple changes in neural dynamics 1 hour after acute stress. Both functional magnetic resonance imaging and electroencephalography show that activity in the cortical salience network and power in high-beta and gamma oscillations increase in less resilient individuals. Contrastingly, activity in the cortical default mode network and spontaneous activity in the posterior hippocampus increase in more resilient individuals. Machine learning analysis confirmed that, 1 hour after stress exposure, the functional connectivity in the salience network was the most influential, followed by that in the default mode network, gamma power, high-beta power, and hippocampal activity. The neurophysiological dynamics for resilience do not occur as previously thought, but rather in a time-lagged manner against stress exposure. Our findings Shed light on a new approach to recovery from stress-induced deficits such as delayed neuromodulation after a stressful event.

neuroscience↗

bioRxiv2023

Divergent evolutionary strategies preempt tissue collision in fly gastrulation

Metazoan development proceeds through a series of morphogenetic events that sculpt body plans and organ structures. In the early embryonic stages, morphogenetic processes involving growth and deformation occur concurrently. Forces generated in one tissue can thus increase mechanical stress in the neighboring tissue, potentially disrupting spatial patterning, morphological robustness, and consequently decreasing organismal fitness. How organisms evolved mechanisms to reduce or release inter-tissue stresses remains poorly understood. Here we combined phylogenetic survey across a whole insect order (Diptera), quantitative live imaging, and functional mechanical perturbation to investigate the evolution of mechanical stress management during epithelial expansions in the gastrulating fly embryos. We find that two distinct cellular mechanisms exist in Diptera to prevent the accumulation of compressive stress that can arise when the expanding head and trunk tissues collide. In Cyclorrhapha, a monophyletic dipteran subgroup including the fruit fly Drosophila melanogaster, the head-trunk boundary undergoes active out-of-plane deformation to form a transient epithelial fold, called the cephalic furrow (CF), which acts as a mechanical sink to preempt head-trunk collision. Genetic or optogenetic elimination of the CF leads to tissue buckling, yielding deleterious effects of axial distortion that likely results from unmitigated release of compressive stress. Non-cyclorrhaphan flies, by contrast, lack CF formation and instead display widespread out-of-plane division in the head, which shortens the duration of its expansion and reduces surface area increase. Reorienting head mitosis in Drosophila from in-plane to out-of-plane partially suppresses the need for epithelial out-of-plane deformation, suggesting that out-of-plane division can act as an alternative mechanical sink to prevent tissue collision. Our data suggest that programs of mechanical stress management can emerge abruptly under selective pressure of inter-tissue mechanical conflict in early embryonic development.

developmental biology↗

bioRxiv2023

KRAS inhibition activates an actionable CD24 do-not-eat-me signal in pancreas cancer

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C- driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a hot tumor immune microenvironment. Immunoprofiling revealed that CD24, a dont eat me signal, is significantly upregulated on cancer cells upon G12Ci treatment. Blocking CD24 enhanced macrophage phagocytosis of cancer cells and significantly sensitized tumors to G12Ci treatment. Similar findings were observed in KRASG12D-driven PDAC. Together, this study reveals common and distinct oncogenic KRAS allele-specific biology and identifies a clinically actionable adaptive mechanism that may improve the efficacy of oncogenic KRAS inhibitor therapy in PDAC. SignificanceGeneration of an autochthonous KRASG12C-driven pancreatic cancer model enabled elucidation of specific effects of KRASG12C during tumor development, revealing CD24 as an actionable adaptive mechanism in cancer cells induced upon KRASG12C inhibition.

cancer biology↗

bioRxiv2023

Differential regulation of the proteome and phosphosproteome along the dorso-ventral axis of the early Drosophila embryo

The initially homogeneous epithelium of the early Drosophila embryo differentiates into regional subpopulations with different behaviours and physical properties that are needed for morphogenesis. The factors at top of the genetic hierarchy that control these behaviours are known, but many of their targets are not. To understand how proteins work together to mediate differential cellular activities, we studied in an unbiased manner the proteomes and phosphoproteomes of the three main cell populations along the dorso-ventral axis during gastrulation using mutant embryos that represent the different populations. We detected 6111 protein groups and 6259 phosphosites of which 3399 and 3433 respectively, were differentially regulated. The changes in phosphosite abundance did not correlate with changes in host protein abundance, showing phosphorylation to be a regulatory step during gastrulation. Hierarchical clustering of protein groups and phosphosites identified clusters that contain known fate determinants such as Doc1, Sog, Snail and Twist. The recovery of the appropriate known marker proteins in each of the different mutants we used validated the approach, but also revealed that two mutations that both interfere with the dorsal fate pathway, Toll10B and serpin27aex do this in very different manners. Diffused network analyses within each cluster point to microtubule components as one of the main groups of regulated proteins. Functional studies on the role of microtubules provide the proof of principle that microtubules have different functions in different domains along the DV axis of the embryo.

developmental biology↗

bioRxiv2022

Estimation of crossbridge-state during cardiomyocyte beating using second harmonic generation

Estimation of dynamic change of crossbridge formation in living cardiomyocytes is expected to provide crucial information for elucidating cardiomyopathy mechanisms, efficacy of an intervention, and other parameters. Here, we developed an assay system to dynamically measure second harmonic generation (SHG) polarization in pulsating cardiomyocyte and proved that the SHG anisotropy derived from myosin filaments in disease-model cardiomyocytes depended on their crossbridge status, providing an evaluation method for myosin force generation. Experiments utilizing an inheritable mutation that induces excessive myosin-actin interactions revealed that the correlation between sarcomere length and SHG anisotropy represents crossbridge formation ratio during pulsation. Furthermore, the present method found that ultraviolet irradiation induced an increased population of attached crossbridges that lost force-generating ability upon myocardial differentiation, causing acquired dysfunction. Taking an advantage of infrared two-photon excitation in SHG microscopy, myocardial dysfunction could be intravitally evaluated in a Drosophila disease model. Thus, along with the establishment of the methodology, we successfully demonstrated the applicability and effectiveness of the present method to evaluate the actomyosin activity of a drug or genetic defect on living cardiomyocytes.

biophysics↗

bioRxiv2022

Establishment of Measles Virus Receptor-expressing Vero Cells Lacking Functional Poliovirus Receptors

Global efforts are underway to eliminate measles and rubella and active viral surveillance is key to achieving this goal. In addition to this, the World Health Organization announced guidelines for handling materials potentially infectious for poliovirus (PV) to minimize the risk of PV reintroduction and achieve PV eradication. To support the global efforts, we have established new PV-non-susceptible cell lines useful for the isolation of measles virus (MeV) and rubella virus (RuV) (Vero {Delta}PVR1/2 hSLAM+). In the cell lines, MeV and RuV replicated efficiently with no concern about PV replication.

microbiology↗

bioRxiv2022

Multi-modal deep neural decoding of visual object representation in humans

Perception and categorization of objects in a visual scene are essential to grasp the surrounding situation. However, it is unclear how neural activities in spatially distributed brain regions, especially in terms of temporal dynamics, represent visual objects. To address this issue, we explored the spatial and temporal organization of visual object representations using concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), combined with neural decoding using deep neural networks (DNNs). Visualization of the fMRI DNN revealed that visual categorization (faces or non-face objects) occurred in brain-wide cortical regions, including the ventral temporal cortex. Interestingly, the EEG DNN valued the earlier phase of neural responses for categorization and the later phase of neural responses for sub-categorization. Combination of the two DNNs improved the classification performance for both categorization and sub-categorization. These deep learning-based results demonstrate a categorization principle in which visual objects are represented in a spatially organized and coarse-to-fine manner.

neuroscience↗

bioRxiv2022

Effects of habitual dart training on hemispheric lateralization in older adults: a cross-sectional study using functional near-infrared spectroscopy

Exercise training integrating physical and cognitive activities is gaining attention because of its potential benefits for brain health. This study focuses on exercise training using a dart game called Wellness Darts. Wellness Darts is a sport involving throwing darts and walking to pull them out of the board, memorizing the score, and subtracting it from the total score, thus allowing the performance of two tasks simultaneously: exercise and calculation. It is expected to maintain and improve cognitive function, and whether the continual dart training affects brain function is of great interest. Before conducting the longitudinal study revealing its effect on brain function, we aimed to cross-sectionally confirm the difference in hemispheric lateralization between expert and non-expert players. Functional near-infrared spectroscopy (fNIRS) was used to measure brain activity for three groups: an expert older group who practiced darts continually, a non-expert older control group, and a non-expert younger control group. Their brain activity patterns were quantified by lateralization index (LI) and compared between groups. The results showed that the younger and the expert older groups had significantly higher LI values than the non-expert older group and did not differ between the expert older and the younger groups. Our results suggest that the Wellness Darts possibly promote hemispheric lateralization.

neuroscience↗

bioRxiv2022

An excitatory-inhibitory fronto-cerebellar loop resolves the Stroop effect

The Stroop effect is a well-known behavioral phenomenon in humans that refers to robust interference between language and color information. Although this effect has long been studied, it remains unclear when the interference occurs and how it is resolved in the brain. By manipulating the verbality of stimulus perception and response generation, here we show that the Stroop effect occurs during perception of color-word stimuli and is resolved by a cross-hemispheric, excitatory-inhibitory functional loop involving the lateral prefrontal cortex and cerebellum. Humans performed a Stroop task and a control task in which the stimulus did not contain verbal information, and made a response either vocally or manually. The resolution of Stroop interference involved the lateral prefrontal cortex in the left hemisphere and the cerebellum in the right hemisphere, independently of whether the response was made vocally or manually. In contrast, such cross-hemispheric lateralization was absent during the non-verbal control task. Moreover, the prefrontal cortex amplified cerebellar activity, whereas the cerebellum suppressed prefrontal activity, and these effects were enhanced during interference resolution. These results suggest that this fronto-cerebellar loop involving language and cognitive systems regulates goal-relevant information to resolve the interference occurring during simultaneous perception of a word and color.

neuroscience↗

bioRxiv2021

Perceptual uncertainty alternates top-down and bottom-up fronto-temporal network signaling during response inhibition

Response inhibition is a primary executive control function that allows the withholding of inappropriate responses, and requires appropriate perception of the external environment to achieve a behavioral goal. It remains unclear, however, how response inhibition is achieved when goal-relevant information involves perceptual uncertainty. Twenty-six human participants of both sexes performed a go/no-go task where visually presented random-dot motion stimuli involved perceptual uncertainties. The right inferior frontal cortex (rIFC) was involved in response inhibition, and the middle temporal (MT) region showed greater activity when dot motions involved less uncertainty. A neocortical temporal region in the superior temporal sulcus (STS) specifically showed greater activity during response inhibition in more perceptually certain trials. In this STS region, activity was greater when response inhibition was successful than when it failed. Directional effective connectivity analysis revealed that in more coherent trials, the MT and STS regions showed enhanced connectivity to the rIFC, whereas in less coherent trials, the signal direction was reversed. These results suggest that a reversible fronto-temporal functional network guides response inhibition under perceptual uncertainty, and in this network, perceptual information in the MT is converted to control information in the rIFC via STS, enabling achievement of response inhibition. Significance statementResponse inhibition refers to withholding inappropriate behavior and is an important for achieving goals. Often, however, decision must be made based on limited environmental evidence. We showed that successful response inhibition is guided by a neocortical temporal region that plays a hub role in converting perceived information coded in a posterior temporal region to control information coded in the prefrontal cortex. Interestingly, when a perceived stimulus becomes more uncertain, the prefrontal cortex supplements stimulus encoding in the temporal regions. Our results highlight fronto-temporal mechanisms of response inhibition in which conversion of stimulus-control information is regulated based on the uncertainty of environmental evidence.

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↗