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Background: Imagination represents a pivotal capability of human intelligence. To develop human-like artificial intelligence, uncovering the computational architecture pertinent to imaginative capabilities through reverse engineering the brain's computational functions is essential. The existing Structure-Constrained Interface Decomposition (SCID) method, leverages the anatomical structure of the brain to extract computational architecture. However, its efficacy is limited to narrow brain regions, making it unsuitable for realizing the function of imagination, which involves diverse brain areas such as the neocortex, basal ganglia, thalamus, and hippocampus., Objective: In this study, we proposed the Function-Oriented SCID method, an advancement over the existing SCID method, comprising four steps designed for reverse engineering broader brain areas. This method was applied to the brain's imaginative capabilities to design a hypothetical computational architecture. The implementation began with defining the human imaginative ability that we aspire to simulate. Subsequently, six critical requirements necessary for actualizing the defined imagination were identified. Constraints were established considering the unique representational capacity and the singularity of the neocortex's modes, a distributed memory structure responsible for executing imaginative functions. In line with these constraints, we developed five distinct functions to fulfill the requirements. We allocated specific components for each function, followed by an architectural proposal aligning each component with a corresponding brain organ., Results: In the proposed architecture, the distributed memory component, associated with the neocortex, realizes the representation and execution function; the imaginary zone maker component, associated with the claustrum, accomplishes the dynamic-zone partitioning function; the routing conductor component, linked with the complex of thalamus and basal ganglia, performs the manipulation function; the mode memory component, related to the specific agranular neocortical area executes the mode maintenance function; and the recorder component, affiliated with the hippocampal formation, handles the history management function. Thus, we have provided a fundamental cognitive architecture of the brain that comprehensively covers the brain's imaginative capacities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yamakawa, Fukawa, Yairi and Matsuo.)

It remains difficult for mobile robots to continue accurate self-localization when they are suddenly teleported to a location that is different from their beliefs during navigation. Incorporating insights from neuroscience into developing a spatial cognition model for mobile robots may make it possible to acquire the ability to respond appropriately to changing situations, similar to living organisms. Recent neuroscience research has shown that during teleportation in rat navigation, neural populations of place cells in the cornu ammonis-3 region of the hippocampus, which are sparse representations of each other, switch discretely. In this study, we construct a spatial cognition model using brain reference architecture-driven development, a method for developing brain-inspired software that is functionally and structurally consistent with the brain. The spatial cognition model was realized by integrating the recurrent state-space model, a world model, with Monte Carlo localization to infer allocentric self-positions within the framework of neuro-symbol emergence in the robotics toolkit. The spatial cognition model, which models the cornu ammonis-1 and -3 regions with each latent variable, demonstrated improved self-localization performance of mobile robots during teleportation in a simulation environment. Moreover, it was confirmed that sparse neural activity could be obtained for the latent variables corresponding to cornu ammonis-3. These results suggest that spatial cognition models incorporating neuroscience insights can contribute to improving the self-localization technology for mobile robots. The project website is https://nakashimatakeshi.github.io/HF-IGL/., Competing Interests: HY was employed by The Whole Brain Architecture Initiative. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nakashima, Otake, Taniguchi, Maeyama, El Hafi, Taniguchi and Yamakawa.)

Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Arai, Kanazawa, Kimura, Munakata, Yamakawa, Shinmura, Yuasa, Sano and Fukuda.)

Post-stroke patients exhibit distinct muscle activation electromyography (EMG) features in sit-to-stand (STS) due to motor deficiency. Muscle activation amplitude, related to muscle tension and muscle synergy activation levels, is one of the defining EMG features that reflects post-stroke motor functioning and motor impairment. Although some qualitative findings are available, it is not clear if and how muscle activation amplitude-related biomechanical attributes may quantitatively reflect during subacute stroke rehabilitation. To better enable a longitudinal investigation into a patient's muscle activation changes during rehabilitation or an inter-subject comparison, EMG normalization is usually applied. However, current normalization methods using maximum voluntary contraction (MVC) or within-task peak/mean EMG may not be feasible when MVC cannot be obtained from stroke survivors due to motor paralysis and the subject of comparison is EMG amplitude. Here, focusing on the paretic side, we first propose a novel, joint torque-based normalization method that incorporates musculoskeletal modeling, forward dynamics simulation, and mathematical optimization. Next, upon method validation, we apply it to quantify changes in muscle tension and muscle synergy activation levels in STS motor control units for patients in subacute stroke rehabilitation. The novel method was validated against MVC-normalized EMG data from eight healthy participants, and it retained muscle activation amplitude differences for inter- and intra-subject comparisons. The proposed joint torque-based method was also compared with the common static optimization based on squared muscle activation and showed higher simulation accuracy overall. Serial STS measurements were conducted with four post-stroke patients during their subacute rehabilitation stay (137 ± 22 days) in the hospital. Quantitative results of patients suggest that maximum muscle tension and activation level of muscle synergy temporal patterns may reflect the effectiveness of subacute stroke rehabilitation. A quality comparison between muscle synergies computed with the conventional within-task peak/mean EMG normalization and our proposed method showed that the conventional was prone to activation amplitude overestimation and underestimation. The contributed method and findings help recapitulate and understand the post-stroke motor recovery process, which may facilitate developing more effective rehabilitation strategies for future stroke survivors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, An, Yang, Kogami, Yoshida, Yamakawa, Hamada, Shimoda, Yamasaki, Yokoyama, Alnajjar, Hattori, Takahashi, Fujii, Otomune, Miyai, Yamashita and Asama.)

Disease-modifying therapies, such as neuroprotective and neurorestorative interventions, are strongly desired for Alzheimer's disease (AD) treatment. Several studies have suggested that histone deacetylase 2 (HDAC2) inhibition can exhibit disease-modifying effects in AD patients. However, whether HDAC2 inhibition shows neuroprotective and neurorestorative effects under neuropathic conditions, such as amyloid β (Aβ)-elevated states, remains poorly understood. Here, we performed HDAC2-specific knockdown in CA1 pyramidal cells and showed that HDAC2 knockdown increased the length of dendrites and the number of mushroom-like spines of CA1 basal dendrites in APP/PS1 transgenic mouse model. Furthermore, HDAC2 knockdown also ameliorated the deficits in hippocampal CA1 long-term potentiation and memory impairment in contextual fear conditioning tests. Taken together, our results support the notion that specific inhibition of HDAC2 has the potential to slow the disease progression of AD through ameliorating Aβ-induced neuronal impairments., Competing Interests: All authors were employed by Shionogi & Co., Ltd. at the time of data collection and manuscript writing. This study received funding from Shionogi & Co., Ltd. The funder had the following involvement with the study: the decision to submit it for publication., (Copyright © 2021 Nakatsuka, Izumi, Tsukamoto, Oyama, Nishitomi, Deguchi, Niidome, Yamakawa, Ito and Ogawa.)

Thyroid hormones (THs) are synthesized in the thyroid gland, and they circulate in the blood to regulate cells, tissues, and organs in the body. In particular, they exert several effects on the cardiovascular system. It is well known that THs raise the heart rate and cardiac contractility, improve the systolic and diastolic function of the heart, and decrease systemic vascular resistance. In the past 30 years, some researchers have studied the molecular pathways that mediate the role of TH in the cardiovascular system, to better understand its mechanisms of action. Two types of mechanisms, which are genomic and non-genomic pathways, underlie the effects of THs on cardiomyocytes. In this review, we summarize the current knowledge of the action of THs in the cardiac function, the clinical manifestation and parameters of their hemodynamics, and treatment principles for patients with hyperthyroid- or hypothyroid-associated heart disease. We also describe the cardiovascular drugs that induce thyroid dysfunction and explain the mechanism underlying the thyroid toxicity of amiodarone, which is considered the most effective antiarrhythmic agent. Finally, we discuss the recent reports on the involvement of thyroid hormones in the regulation of myocardial regeneration and metabolism in the adult heart., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yamakawa, Kato, Noh, Yuasa, Kawamura, Fukuda and Aizawa.)

To understand the function of the neocortex, which is a hierarchical distributed network, it is useful giving meaning to the signals transmitted between these areas from the computational viewpoint. The overall anatomical structure or organs related to this network, including the neocortex, thalamus, and basal ganglia, has been roughly revealed, and much physiological knowledge, though often fragmentary, is being accumulated. The computational theories involving the neocortex have also been developed considerably. By introducing the assumption "The signals transmitted by interarea axonal projections of pyramidal cells in the neocortex carry different meanings for each cell type, common to all areas," derived from its nature as a distributed network in the neocortex, allows us to specify the computational meanings of interarea signals. In this paper, first, the types of signals exchanged between neocortical areas are investigated, taking into account biological constraints, and employing theories such as predictive coding, reinforcement learning, representation emulation theory, and BDI logic as theoretical starting points, two types of feedforward signals (observation and deviation) and three types of feedback signals (prediction, plan, and intention) are identified. Next, based on the anatomical knowledge of the neocortex and thalamus, the pathways connecting the areas are organized and summarized as three corticocortical pathways and two thalamocortical pathways. Using this summation as preparation, this paper proposes a hypothesis that gives meaning to each type of signals transmitted in the different pathways in the neocortex, from the viewpoint of their functions. This hypothesis reckons that the feedforward corticocortical pathway transmits observation signals, the feedback corticocortical pathway transmits prediction signals, and the corticothalamic pathway mediated by core relay cells transmits deviation signals. The thalamocortical pathway, which is mediated by matrix relay cells, would be responsible for transmitting the signals that activate a part of prediction signals as intentions, due to the reason that the nature of the other available feedback pathways are not sufficient for conveying plans and intentions as signals. The corticocortical pathway, which is projected from various IT cells to the first layer, would be responsible for transmitting signals that activate a part of prediction signals as plans., (Copyright © 2020 Yamakawa.)

Since nitrogenase is extremely vulnerable to oxygen, aerobic or micro-aerobic nitrogen-fixing organisms need to create anaerobic microenvironments in the cells for diazotrophic growth, which would be one of the major barriers to express active nitrogenase in plants in efforts to create nitrogen-fixing plants. Numerous cyanobacteria are able to fix nitrogen with nitrogenase by coping with the endogenous oxygen production by photosynthesis. Understanding of the molecular mechanisms enabling to the coexistence of nitrogen fixation and photosynthesis in nonheterocystous cyanobacteria could offer valuable insights for the transfer of nitrogen fixation capacity into plants. We previously identified the cnfR gene encoding the master regulator for the nitrogen fixation ( nif ) gene cluster in the genome of a nonheterocystous cyanobacterium Leptolyngbya boryana , in addition to initial characterization of the nif gene cluster. Here we isolated nine mutants, in which the nif and nif -related genes were individually knocked out in L. boryana to investigate the individual functions of (1) accessory proteins (NifW, NifX/NafY, and NifZ) in the biosynthesis of nitrogenase metallocenters, (2) serine acetyltransferase (NifP) in cysteine supply for iron-sulfur clusters, (3) pyruvate formate lyase in anaerobic metabolism, and (4) NifT and HesAB proteins. ΔnifW , ΔnifXnafY , and ΔnifZ exhibited the most severe phenotype characterized by low nitrogenase activity (<10%) and loss of diazotrophic growth ability. The phenotypes of ΔnifX , ΔnafY , and ΔnifXnafY suggested that the functions of the homologous proteins NifX and NafY partially overlap. ΔnifP exhibited significantly slower diazotrophic growth than the wild type, with lower nitrogenase activity (22%). The other four mutants ( ΔpflB , ΔnifT , ΔhesA , and ΔhesB ) grew diazotrophically similar to the wild type. Western blot analysis revealed a high correlation between nitrogenase activity and NifD contents, suggesting that NifD is more susceptible to proteolytic degradation than NifK in L. boryana . The phenotype of the mutants lacking the accessory proteins was more severe than that observed in heterotrophic bacteria such as Azotobacter vinelandii , which suggests that the functions of NifW, NifX/NafY, and NifZ are critical for diazotrophic growth of oxygenic photosynthetic cells. L. boryana provides a promising model for studying the molecular mechanisms that produce active nitrogenase, to facilitate the creation of nitrogen-fixing plants.

The sit-to-stand motion is a common movement in daily life and understanding the mechanism of the sit-to-stand motion is important. Our previous study shows that four muscle synergies can characterize the sit-to-stand motion, and they have specific roles, such as upper body flexion, rising from a chair, body extension, and posture stabilization. The time-varying weight of these synergies are changed to achieve adaptive movement. However, the relationship between sensory input and the activation of the muscle synergies is not completely understood. In this paper, we aim to clarify how vestibular and visual inputs affect the muscle synergy in sit-to-stand motion. To address this, we conducted experiments as follows. Muscle activity, body kinematics, and ground reaction force were measured for the sit-to-stand motion under three different conditions: control, visual-disturbance, and vestibular-disturbance conditions. Under the control condition, the participants stood without any intervention. Under the visual-disturbance condition, the participants wore convex lens glasses and performed the sit-to-stand motion in a dark room. Under the vestibular-disturbance condition, a caloric test was performed. Muscle synergies were calculated for these three conditions using non-negative matrix factorization. We examined whether the same four muscle synergies were employed under each condition, and the changes in the time-varying coefficients were determined. These experiments were conducted on seven healthy, young participants. It was found that four muscle synergies could explain the muscle activity in the sit-to-stand motion under the three conditions. However, there were significant differences in the time-varying weight coefficients. When the visual input was disturbed, a larger amplitude was found for the muscle synergy that activated mostly in the final posture stabilization phase of the sit-to-stand motion. Under vestibular-disturbance condition, a longer activation was observed for the synergies that extended the entire body and led to posture stabilization. The results implied that during human sit-to-stand motion, visual input has less contribution to alter or correct activation of muscle synergies until the last phase. On the other hand, duration of muscle synergies after the buttocks leave are prolonged in order to adapt to the unstable condition in which sense of verticality is decreased under vestibular-disturbance.

Global warming impairs grain filling in rice and reduces starch accumulation in the endosperm, leading to chalky-appearing grains, which damages their market value. We found previously that high temperature-induced expression of starch-lytic α-amylases during ripening is crucial for grain chalkiness. Because the rice genome carries at least eight functional α-amylase genes, identification of the α-amylase(s) that contribute most strongly to the production of chalky grains could accelerate efficient breeding. To identify α-amylase genes responsible for the production of chalky grains, we characterized the histological expression pattern of eight α-amylase genes and the influences of their overexpression on grain appearance and carbohydrate components through a series of experiments with transgenic rice plants. The promoter activity of most α - amylase genes was elevated to various extents at high temperature. Among them, the expression of Amy1A and Amy3C was induced in the internal, especially basal to dorsal, region of developing endosperm, whereas that of Amy3D was confined near the ventral aleurone. These regions coincided with the site of occurrence of chalkiness, which was in clear contrast to conventionally known expression patterns of the enzyme in the scutellum and aleurone during seed germination. Furthermore, overexpression of α-amylase genes, except for Amy3E , in developing endosperm produced various degrees of chalky grains without heat exposure, whereas that of Amy3E yielded normal translucent grains, as was the case in the vector control, even though Amy3E -overexpressing grains contained enhanced α-amylase activities. The weight of the chalky grains was decreased due to reduced amounts of starch, and microscopic observation of the chalky part of these grains revealed that their endosperm consisted of loosely packed round starch granules that had numerous pits on their surface, confirming the hydrolysis of the starch reserve by α-amylases. Moreover, the chalky grains contained increased amounts of soluble sugars including maltooligosaccharides at the expense of starch. The integrated analyses proposed that expression of Amy1A, Amy3C , and Amy3D at the specific regions of the developing endosperm could generate the chalkiness. This finding provides the fundamental knowledge to narrow down the targets for the development of high temperature-tolerant premium rice.

Sense of agency (SoA) refers to the feeling of controlling one's own actions, and the experience of controlling external events with one's actions. The present study examined the effect of strength of intentional effort on SoA. We manipulated the strength of intentional effort using three types of buttons that differed in the amount of force required to depress them. We used a self-attribution task as an explicit measure of SoA. The results indicate that strength of intentional effort enhanced self-attribution when action-effect congruency was unreliable. We concluded that intentional effort importantly affects the integration of multiple cues affecting explicit judgments of agency when the causal relationship action and effect was unreliable.

Body representation refers to perception, memory, and cognition related to the body and is updated continuously by sensory input. The present study examined the influence of goals on body representation updating with two experiments of the rubber hand paradigm. In the experiments, participants moved their hidden left hands forward and backward either in response to instruction to touch a virtual object or without any specific goal, while a virtual left hand was presented 250 mm above the real hand and moved in synchrony with the real hand. Participants then provided information concerning the perceived heights of their real left hands and rated their sense of agency and ownership of the virtual hand. Results of Experiment 1 showed that when participants moved their hands with the goal of touching a virtual object and received feedback indicating goal attainment, the perceived positions of their real hands shifted more toward that of the virtual hand relative to that in the condition without a goal, indicating that their body representations underwent greater modification. Furthermore, results of Experiment 2 showed that the effect of goal-directed movement occurred in the active condition, in which participants moved their own hands, but did not occur in the passive condition, in which participants' hands were moved by the experimenter. Therefore, we concluded that the sense of agency probably contributed to the updating of body representation involving goal-directed movement.