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This is a grant proposal for Qualia Structure B (2020-2023).

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are two types of cortical projection neurons (CPNs): those that project locally and interhemispherically and those that project to subcerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here, we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during mouse brain formation. We show thatMllt11expression is exclusive to developing neurons and is enriched in the developing cortical plate (CP) during the formation of the superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditional loss-of-function and gain-of-function analysis we show that Mllt11 is required for neuritogenesis and proper migration of upper layer CPNs. Loss ofMllt11in the superficial cortex of male and female neonates leads to a severe reduction in fibers crossing the corpus callosum (CC), a progressive loss in the maintenance of upper layer projection neuron gene expression, and reduced complexity of dendritic arborization. Proteomic analysis revealed that Mllt11 associates with stabilized microtubules, andMllt11loss affected microtubule staining in callosal axons. Taken together, our findings support a role for Mllt11 in promoting the formation of mature upper-layer neuron morphologies and connectivity in the cerebral cortex.SIGNIFICANCE STATEMENTThe regulation of cortical projection neuron (CPN) morphologies is an area of active investigation since the time of Cajal. Yet the molecular mechanisms of how the complex dendritic and axonal morphologies of projection neurons are formed remains incompletely understood. Although conditional mutagenesis analysis in the mouse, coupled with overexpression assays in the developing fetal brain, we show that a novel protein called Mllt11 is sufficient and necessary to regulate the dendritic and axonal characteristics of callosal projection neurons in the developing mammalian neocortex. Furthermore, we show that Mllt11 interacts with microtubules, likely accounting for its role in neuritogenesis.

フランスの哲学者Rene Descartesのコトギ「我思う、ゆえに、我あり」は、何かを意識しているのは私であるという自覚が、人間の意識体験に宿っていることを言いあらわしている。このような自覚は、意識している自分を俯瞰する意識（意識していることへの意識）であり、意識の究極のレベルに位置づけられるものである。本稿では、意識していることへの意識が何を指すのかを整理し、脳が脳自体の状態を語り得る不思議について、再帰性という観点から考察する

DNA transposable elements and transposase-derived genes are present in most living organisms, including vertebrates, but their function is largely unknown. PiggyBac Transposable Element Derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase-derived gene with retained nuclease activity in cells. Vertebrate brain development is known to be associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. Here, we show that PGBD5 contributes to normal brain development in mice and humans, where its deficiency causes disorder of intellectual disability, movement and seizures. In mice, Pgbd5 is required for the developmental induction of post-mitotic DNA breaks and recurrent somatic genome rearrangements in neurons. Together, these studies nominate PGBD5 as the long-hypothesized neuronal DNA nuclease required for brain function in mammals.One-Sentence SummaryPiggyBac Transposable Element Derived 5 (PGBD5) is required for brain development in humans and mice by promoting somatic neuronal genome rearrangements.

This manuscript discusses the recent report “Cognate restriction of transposition bypiggyBac-like proteins” inNucleic Acids Researchby Beckermann et al and related recent publications about the inability to detect DNA transposition activity of human domesticated DNA transposase PGBD5. Measuring DNA transposition activity of transposases in human cells, where these enzymes can act on endogenous genomic substrates and induce DNA damage, is complicated by these and other cellular responses. Possible reasons for the discordant findings of Beckermann et al with prior independent reports of PGBD5 DNA transposition by Helou et al and Henssen et al and specific details of experimental methods in human cells are presented. In particular, by using independent experiments that reproduce PGBD5-mediated genomic integration, we demonstrate how supraphysiologic and ectopic overexpression of PGBD5 can cause DNA damage and cell death, and artifactual loss of apparent activity in clonogenic transposition reporter assays. While PGBD5 can support apparent DNA transposition, its cellular activity predominantly involves double-strand DNA breaks, deletions and other DNA rearrangements. We discuss the implications of this phenomenon for the interpretation of experimental assays and activities of domesticated DNA transposases.

The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

Histamine H3 receptor antagonists and inverse agonists have been extensively developed to treat sleep–wake, neurocognitive, and allied disorders. However, potential adverse effects, including insomnia, hampered the clinical use of these drugs, possibly due to their persistent interaction with the target molecules. The purpose of the present study was to estimate the pharmacokinetics and pharmacodynamics of enerisant, a novel antagonist and inverse agonist for histamine H3 receptors. To measure the histamine H3 receptor occupancy by enerisant, positron emission tomography studies using [11C]TASP457, a specific radioligand for histamine H3 receptors, were performed in 12 healthy men at baseline and at 2 h after oral administration of enerisant hydrochloride. For three of these subjects, two additional scans were performed at 6 and 26 h after the administration. Relationships between the receptor occupancy by enerisant and its dose and plasma concentrations were then analyzed. Administration of enerisant hydrochloride decreased the radioligand binding in a dose-dependent manner. The estimated receptor occupancy values at 2 h varied as a function of its dose or plasma concentration. The time course of the occupancy showed persistently high levels (> 85%) in the two subjects with higher doses (25 and 12.5 mg). The occupancy was also initially high at 2 h and 6 h with the lower dose of 5 mg, but it decreased to 69.7% at 26 h. The target engagement of enerisant was demonstrated in the brains of living human subjects. The occupancy of histamine H3 receptors by enerisant at 2 h can be predicted by applying the plasma concentration of enerisant to Hill’s plot. The preliminary time-course investigation showed persistently high brain occupancy with high doses of enerisant despite the decreasing plasma concentration of the drug. Five milligrams or less dose would be appropriate for the treatment for narcolepsy with initially high occupancy allowing for effective treatment of narcolepsy, and then the occupancy level would be expected to decrease to a level to avoid this drug’s unwanted side effect of insomnia at night, although further research is warranted to confirm the statement since the expected decrease is based on the finding in one subject. This study was retrospectively registered with ClinicalTrials.gov (NCT04631276) on November 17, 2020.

Histamine H receptor antagonists and inverse agonists have been extensively developed to treat sleep-wake, neurocognitive, and allied disorders. However, potential adverse effects, including insomnia, hampered the clinical use of these drugs, possibly due to their persistent interaction with the target molecules. The purpose of the present study was to estimate the pharmacokinetics and pharmacodynamics of enerisant, a novel antagonist and inverse agonist for histamine H receptors.

Humans are typically inept at evaluating their abilities and predispositions, while often disregarding such lack of metacognitive insight into their capacities and even augmenting (albeit illusorily) self-evaluation such that they should have more desirable traits than an average peer. This superiority illusion helps maintain a healthy mental state. However, the scope and range of its influence on broader human behavior, especially perceptual tasks, remain elusive. As belief shapes the way people perceive and recognize, the illusory self-superiority belief potentially regulates our perceptual and metacognitive performance. In this study, we used hierarchical Bayesian estimation and machine learning of signal detection theoretic measures to understand how superiority illusion influences visual perception and metacognition for Ponzo illusion. Our results demonstrated that superiority illusion correlated with visual illusion magnitude and metacognitive performance. Next, we used machine learning with a relaxed elastic net and unveiled the latent architecture that underlies the correlations. We revealed that the “extraversion” superiority dimension tapped into visual illusion magnitude and metacognitive ability. In contrast, the “honesty-humility” and “neuroticism” dimensions were only predictive of visual illusion magnitude and metacognitive ability, respectively. These results suggest common and distinct influences of superiority features on perceptual sensitivity and metacognition. Our findings contribute to the accumulating body of evidence indicating that the superiority illusion leverage is far-reaching, even to visual perception.Significance StatementsPeople have a cognitive bias to overestimate their abilities above the mean (superiority illusion) and thereby help maintain a healthy mental state. In this work, we show that the influences of superiority illusion are more extensive than previously thought. We find that superiority illusion correlated with visual illusion magnitude and metacognitive performance. Furthermore, using hierarchical Bayesian estimation and machine learning, we unveil the latent architecture (i.e., overlapping yet dissociable superiority features) that predicts visual illusion magnitude and metacognitive performance. These findings suggest that superiority illusion is a cardinal cognitive bias that involves a vast assortment of behavior as an illusion is an efficient and adaptive tool for humans to somehow thrive in a world of ambiguity.

優越の錯覚とは、自己の能力や性格を過大評価する傾向を指し、未来への希望や目標に向かう動機づけとなると考えられている。一方、抑うつの現実主義として知られるように、抑うつ状態においては現実的に自分自身をとらえてしまう傾向があり、優越の錯覚を持つことは心の健康に重要な役割を果たすと考えられている。しかし、内観に基づく優越の錯覚が、自ら意識することのできない潜在的な優越感とどのように関係し、抑うつ症状と関連するかは不明である。本研究では、健常者を対象に、優越の錯覚と潜在的優越感を測定し、抑うつに関わる絶望感と内発的動機づけに関わる認知欲求との関連を検討した。結果、優越の錯覚が潜在的優越感よりも低く、その不一致度が大きいほど、絶望感が高く、認知欲求が低いことが判明した。内観による優越の錯覚が低い一方で無意識な優越感が高い状態は、絶望感や意欲低下など抑うつ症状の予測因子となりうる可能性が示唆された。

The orexinergic system plays a significant role in regulating proper sleep/wake maintenance. Dual orexin receptor antagonist (DORA) is widely prescribed for insomnia symptoms. The antagonist acts on orexin 1 and 2 receptors located in certain brain areas, including the locus coeruleus and dorsal raphe. Nevertheless, its effects on monoamine-related gene expression remain unclear. Here, we measured the expression levels of monoamine-related genes in DORA-treated mice. DORA treatment significantly affected overall levels of noradrenalin transporter/monoamine oxidases A mRNA expression in the hippocampus. Our findings suggest that DORA contributes to noradrenalin-related gene expression regulation in the central nervous system.

Genomic rearrangements are a hallmark of most solid tumors, including medulloblastoma, one of the most common brain tumors in children. Childhood cancers involve dysregulated cell development, but their mutational causes remain largely unknown. One of the most common forms of medulloblastoma is caused by ectopic activation of Sonic Hedgehog (SHH) signaling in cerebellar granule cell progenitors, associated with genetic deletions, amplifications, and other oncogenic chromosomal rearrangements. Here, we show that PiggyBac Transposable Element Derived 5 (Pgbd5) promotes tumor development in multiple developmentally-accurate mouse models of SHH medulloblastoma. Most mice with Pgbd5 deficiency do not develop tumors, while Pgbd5-deficient mice maintain largely normal cerebellar development. Mouse medulloblastomas expressing Pgbd5 exhibit significantly increased numbers of somatic structural DNA rearrangements, with PGBD5-specific transposon sequences at their breakpoints. Similar sequence breakpoints recurrently affect somatic DNA rearrangements of known tumor suppressors and oncogenes in medulloblastomas in 329 children. Therefore, this study identifies PGBD5 as a primary medulloblastoma mutator and provides a genetic mechanism responsible for the generation of somatic oncogenic DNA rearrangements in childhood cancer.One-Sentence SummaryInduction of somatic oncogenic mutations by the DNA transposase PGBD5 in cerebellar progenitor cells promotes medulloblastoma development.

認知・行動療法，精神力動的心理療法といった精神療法の神経基盤を感情調節の観点から概説したうえで，感情調節の神経基盤に直接アプローチする技法であるニューロフィードバック訓練についても紹介し，従来の精神療法とニューロフィードバック訓練の違いや両者の特長について考察した。

In evaluating the personality attributes and performance of the self, people are inclined to view themselves superior to others, a phenomenon known as superiority illusion (SI). This illusive outlook pervades people’s thoughts, creating hope for the future and promoting mental health. Although a specific cortico-striatal functional connectivity (FC) under dopaminergic modulation was previously shown to be implicated in SI, the underlying whole-brain mechanisms have remained unclarified. Herein, to reveal the neural network subserving individual’s SI, we conducted a data-driven, machine-learning investigation to explore the resting-state FC network across the whole brain. Using the locally-acquired resting-state functional magnetic resonance imaging data (n = 123), we identified a set of 15 FCs most informative in classifying individuals with higher-versus lower-than-average levels of SI in evaluating positive trait words (area under the curve [AUC] = 0.81). Among the 15 FCs, the contribution level to the classification was 11% by the previously-highlighted cortico-striatal FC alone, but 60% by the encompassing cortico-limbico-striatal network cluster. A newly-identified, cortico-thalamic FC and another FC cluster also demonstrated substantial contribution. The classification accuracy was generalized into an independent cohort (n = 36; AUC = 0.73). Importantly, using the same set of 15 FCs, we achieved prediction on an individual’s level of striatal dopamine D2 receptor availability (Pearson correlation, r = 0.46, P = 0.005). This is the first successful identification of the whole-brain neural network that simultaneously predicts the behavioral manifestation and molecular underpinning of an essential psychological process that promotes well-being and mental health.Significance StatementSuperiority illusion (SI) is a basic self-referential framework that pervades people’s thoughts and promotes well-being and mental health. An aberrant form of SI has been reported in psychiatric conditions such as depression. Our hypothesis-free, data-driven investigation revealed the spatially-distributed neural network that for the first time achieved prediction on an individual’s levels of SI and the striatal dopaminergic transmission simultaneously. In principle, this multiple-biological-layer framework can be applicable to any behavioral trait to establish a link with its underlying neural network and neurochemical properties, which could quantitatively present the relation of its aberrant form with the pathophysiology of neuropsychiatric disorders. Future clinical research may aid in deriving a diagnostic biomarker for examining the related behavioral and neurochemical characteristics within individuals.

In evaluating the personality attributes and performance of the self, people are inclined to view themselves superior to others, a phenomenon known as superiority illusion (SI). This illusive outlook pervades people’s thoughts, creating hope for the future and promoting mental health. Although a specific cortico-striatal functional connectivity (FC) under dopaminergic modulation was previously shown to be implicated in SI, the underlying whole-brain mechanisms have remained unclarified. Herein, to reveal the neural network subserving individual’s SI, we conducted a data-driven, machine-learning investigation to explore the resting-state FC network across the whole brain. Using the locally-acquired resting-state functional magnetic resonance imaging data (n = 123), we identified a set of 15 FCs most informative in classifying individuals with higher-versus lower-than-average levels of SI in evaluating positive trait words (area under the curve [AUC] = 0.81). Among the 15 FCs, the contribution level to the classification was 11% by the previously-highlighted cortico-striatal FC alone, but 60% by the encompassing cortico-limbico-striatal network cluster. A newly-identified, cortico-thalamic FC and another FC cluster also demonstrated substantial contribution. The classification accuracy was generalized into an independent cohort (n = 36; AUC = 0.73). Importantly, using the same set of 15 FCs, we achieved prediction on an individual’s level of striatal dopamine D2 receptor availability (Pearson correlation, r = 0.46, P = 0.005). This is the first successful identification of the whole-brain neural network that simultaneously predicts the behavioral manifestation and molecular underpinning of an essential psychological process that promotes well-being and mental health. Significance Statement Superiority illusion (SI) is a basic self-referential framework that pervades people’s thoughts and promotes well-being and mental health. An aberrant form of SI has been reported in psychiatric conditions such as depression. Our hypothesis-free, data-driven investigation revealed the spatially-distributed neural network that for the first time achieved prediction on an individual’s levels of SI and the striatal dopaminergic transmission simultaneously. In principle, this multiple-biological-layer framework can be applicable to any behavioral trait to establish a link with its underlying neural network and neurochemical properties, which could quantitatively present the relation of its aberrant form with the pathophysiology of neuropsychiatric disorders. Future clinical research may aid in deriving a diagnostic biomarker for examining the related behavioral and neurochemical characteristics within individuals.

Binocular rivalry refers to a phenomenon in which the perceived image changes spontaneously over time when the two eyes are presented with different images. The purpose of this study is to test whether the violation of temporal Bell inequality can be experimentally observed in binocular rivalry. If the temporal Bell inequality is violated (under no-signaling in time: NSIT), it implies that the perception of the rival stimuli cannot be assumed to be definite at each point in time (i.e., “realism” in the corresponding mental representations is violated), which is a key indication of non-classical behavior (as in, for example, quantum-like systems). Here, to test the violation of the inequality, we used binocular rivalry and measured both subjective reports and electroencephalogram (EEG). With EEG, we used frequency-tagging technique to track the cortical signal driven by each eye’s stimulus, known as the steady-state visual evoked potential (SSVEP). We present the conceptual and methodological approaches to test the temporal Bell inequality., Quantum Innovation 2021

Introduction The purpose of the present study is to investigate quantum-like properties of mental states in bistable perception. In order to do this, we tested whether the temporal Bell inequality applied to bistable perception experiments[1] can be violated. In the present study, we used visual stimuli [2], where we can continuously and systematically manipulate two types of ambiguities in the perceived rotation of dots. When the rotation angle is large, the stimuli induce bistable percept. When the angle is small, the direction of rotation of the stimuli becomes difficult to judge. We use the stimuli to test if the temporal Bell inequality can be violated, and if so, under what parameter regime, it can be violated. Method Two patterns were presented alternately: a visual stimulus consisting of four disks, and one in which the disks were rotated by a specific angle (5-45 degrees) in each trial [FIG. 1(A)]. When the angle of rotation was close to 45 degrees, stimuli were perceived to rotate in one of the two directions for a while with occasional reversals at random times (i.e., bistable perception). When the angle of rotation was close to 5 degrees, no rotation was perceived beyond the angle of rotation of the stimulus, and left and right rotations were perceived alternately, but the angle of rotation was so small that it was difficult to determine the direction of rotation [FIG. 1(B)]. At two time points after the beep, the participants responded by pressing a button in the direction of rotation that they saw at that time [FIG. 1(C)]. Reference 1H. Atmanspacher, and T. Filk, J. Math. Psychol. 54, 314-321 (2010). 2S. Takei and S. Nishida, J. Vision. 10, 23 (2010). 3M. M. Wilde and A. Mizel, Found. Phys. 42, 256 (2012). Acknowledgement This work was supported by JSPS KAKENHI JP20H05711 and MEXT Q-LEAP Grant Number JPMXS0120330644., The 4th international forum on quantum metrology and sensing / Quantum innovation 2021

Neurofeedback (NF) aptitude, which refers to an individual's ability to change brain activity through NF training, has been reported to vary significantly from person to person. The prediction of individual NF aptitudes is critical in clinical applications to screen patients suitable for NF treatment. In the present study, we extracted the resting-state functional brain connectivity (FC) markers of NF aptitude, independent of NF-targeting brain regions. We combined the data from fMRI-NF studies targeting four different brain regions at two independent sites (obtained from 59 healthy adults and six patients with major depressive disorder) to collect resting-state fMRI data associated with aptitude scores in subsequent fMRI-NF training. We then trained the multiple regression models to predict the individual NF aptitude scores from the resting-state fMRI data using a discovery dataset from one site and identified six resting-state FCs that predicted NF aptitude. Subsequently, the reproducibility of the prediction model was validated using independent test data from another site. The identified FC model revealed that the posterior cingulate cortex was the functional hub among the brain regions and formed predictive resting-state FCs, suggesting that NF aptitude may be involved in the attentional mode-orientation modulation system's characteristics in task-free resting-state brain activity.

The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. To clarify the association between individual variations in behavioral inhibition system and brain 5-HT

Positron emission tomography (PET) with [First, the reproducibility of BP estimation using the dual-bolus injection approach was evaluated using PET scans without stimulation in nine healthy volunteers. A 90-min scan was performed with bolus injections of [In the PET scans without stimulation, the dual-bolus injection approach showed a smaller MAD (2%) between BPOur results indicate that the cognitive task-induced changes in dopamine-related systems may be complex and difficult to measure accurately using PET scans. However, the proposed dual-bolus injection approach provided reliable BP estimates with high reproducibility, suggesting that it has the potential to improve the accuracy of PET scans for measuring changes in dopamine concentrations.

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are generally two types of cortical projection neurons: those that project locally and interhemispherically, and those that project to sub-cerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate, particularly during the formation of the upper or superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditional loss-of-function and gain-of-function analysis we show that Mllt11 is a required for neuritogenesis and proper migration of upper layer cortical projection neurons. Loss of Mllt11 in the superficial cortex leads to a severe reduction in fibres crossing the corpus callosum, a progressive loss in the maintenance of upper layer projection neuron gene expression, and dysplasia of dendritic arborisation patterns. Proteomic analysis revealed that Mllt11 associates with cytoskeletal components including stabilized microtubules consistent with a role in neuronal migration and neuritogenesis. Taken together, our findings support a role for Mllt11 in promoting the formation of mature projection neuron morphologies and connectivity in the cerebral cortex.

Some psychiatric diseases are associated with disruptions in the circadian clock system. Ziprasidone (ZIP), a second-generation antipsychotic, is widely used for psychiatry-related pharmacotherapy but its mechanism has not been clearly elucidated. We measured clock gene fluctuation patterns in the hippocampus and the amygdala in ZIP-treated mice. ZIP significantly increased Per1, Per2, and Bmal1 mRNA 2 h after the lights were turned off (ZT14) in the hippocampus, but not in the amygdala. These results suggest that ZIP might affect clock gene regulation, which could represent the pathway underlying symptom amelioration.

Esaxerenone is a novel non-steroidal mineralocorticoid receptor antagonisit (MR blocker), whose unique binding to the MR-ligand domain yields a stronger MR antagonistic effect and higher selectivity than existing MR antagonisits. Esaxerenone was approved for the treatment of hypertension in Japan in January 2019. Esaxerenone suppresses the reduction of urinary Na+/K+ ratio in adrenalectomized rats and blood pressure increase, proteinuria, and renal tissue lesions in salt-sensitive hypertensive rats-all in a dose-dependent manner. Esaxerenone is rapidly absorbed and reaches intracellular targets because of its high membrane permeability, exhibits high bioavailability with small interindividual exposure variation, and is metabolized via several pathways (e.g., oxidation, glucuronidation, and hydrolysis), which is associated with low drug-drug interaction risk. As esaxerenone is slightly excreted into urine, its exposure is similar between elderly and non-elderly patients, and between patients with normal and moderately deteriorated renal function. Given its 19-hour half-life, once-daily administration would have a sustainable antihypertensive effect. The ESAX-HTN phase 3 study demonstrated the non-inferiority of esaxerenone's antihypertensive effect versus that of eplerenone in essential hypertension. Another study showed a stable antihypertensive effect for 52 weeks as monotherapy or combination therapy. In hypertensive patients with moderate impairment or both type 2 diabetes and albuminuria treated with a renin-angiotensin system inhibitor, esaxerenone elicited a stable antihypertensive effect and manageable hyperkalemia incidence with titration from a low dose and monitoring including serum potassium. Thus, with careful monitoring of serum potassium, esaxerenone can be administered to patients with moderate renal impairment or both diabetes and albuminuria.

Objective: Positron emission tomography (PET) scans of imaging receptors require 60–90-min dynamic acquisition for quantitative analysis. Head movement is often observed during scanning, which hampers the reliable estimation of quantita- tive parameters. This study evaluated image-based motion correction by frame-to-frame realignment for PET studies with [11C]raclopride and [11C]FLB 457 acquired by an Eminence SET-3000GCT/X and investigated the effect of this correction on the quantitative outcomes. Methods: First, an optimal method for estimating motion parameters was evaluated by computer simulation. Simulated emis- sion sinograms were reconstructed to the PET images with or without attenuation correction using a μ-map of the transmis- sion scan. Six motion parameters were estimated frame-by-frame by registering each frame of the PET images to several types of reference images and the reliability of registration was compared. Next, in [11C]raclopride and [11C]FLB 457 studies in normal volunteers, six motion parameters for each frame were estimated by the registration method determined from the simulation results. Head movement was corrected by realigning the PET images reconstructed with a motion-included μ-map in which a mismatch between the transmission and emission scans was corrected. After this correction, time-activity curves (TAC) for the striatum or cerebral cortex were obtained and the binding potentials of the receptors (BPND) were estimated using the simplified reference tissue model. Results: In the simulations, the motion parameters could be reliably estimated by registering each frame of the non-attenua- tion-corrected PET images to their early-phase frame. The motion parameters in the human studies were also obtained using the same method. After correction, a discontinuity of TACs in the striatum and cerebral cortex was remarkably improved and the BPND values in these regions increased. Compared to the motion-corrected PET images reconstructed using the measured μ-map, the images reconstructed using the motion-included μ-map did not result in a remarkable improvement of BPND in the striatum of [11C]raclopride studies, while the BPND in the cerebral cortex changed in some [11C]FLB 457 studies in which large head movement was observed. Conclusions: In PET receptor imaging, head movement during dynamic scans can be corrected by frame-to-frame realign- ment. This method is easily applicable to clinical studies and provides reliable TACs and BPND.

Positron emission tomography (PET) scans of imaging receptors require 60–90-min dynamic acquisition for quantitative analysis. Head movement is often observed during scanning, which hampers the reliable estimation of quantitative parameters. This study evaluated image-based motion correction by frame-to-frame realignment for PET studies with [11C]raclopride and [11C]FLB 457 acquired by an Eminence SET-3000GCT/X and investigated the effect of this correction on the quantitative outcomes. First, an optimal method for estimating motion parameters was evaluated by computer simulation. Simulated emission sinograms were reconstructed to the PET images with or without attenuation correction using a µ-map of the transmission scan. Six motion parameters were estimated frame-by-frame by registering each frame of the PET images to several types of reference images and the reliability of registration was compared. Next, in [11C]raclopride and [11C]FLB 457 studies in normal volunteers, six motion parameters for each frame were estimated by the registration method determined from the simulation results. Head movement was corrected by realigning the PET images reconstructed with a motion-included µ-map in which a mismatch between the transmission and emission scans was corrected. After this correction, time-activity curves (TAC) for the striatum or cerebral cortex were obtained and the binding potentials of the receptors (BPND) were estimated using the simplified reference tissue model. In the simulations, the motion parameters could be reliably estimated by registering each frame of the non-attenuation-corrected PET images to their early-phase frame. The motion parameters in the human studies were also obtained using the same method. After correction, a discontinuity of TACs in the striatum and cerebral cortex was remarkably improved and the BPND values in these regions increased. Compared to the motion-corrected PET images reconstructed using the measured µ-map, the images reconstructed using the motion-included µ-map did not result in a remarkable improvement of BPND in the striatum of [11C]raclopride studies, while the BPND in the cerebral cortex changed in some [11C]FLB 457 studies in which large head movement was observed. In PET receptor imaging, head movement during dynamic scans can be corrected by frame-to-frame realignment. This method is easily applicable to clinical studies and provides reliable TACs and BPND.

For becoming a talented pharmacist at a health support pharmacy, the practitioner must obtain ability in two significant skill sets: "Technical skill" and "Non-technical skill". Technical skills are that required for a pharmacist's specialty/expertise, such as a wide variety of specialized knowledge and techniques. Non-technical skills are those required for effective communication and cooperation with patients, as well as with professionals from multiple fields, and also leadership/problem-solving ability within a team. Therefore, technical skill and non-technical skill go hand-in-hand like the two wheels on an axle. In a community-based integrated care system, medical professionals are expected to support a patient's overall health more effectively, even extending into his/her private life. In order to enable pharmacists to expand their scope of activity and fully execute their expertise, Yakugaku Seminar Lifelong Learning Center supports pharmacists from the standpoint of education with various themes, for example: the simulated experience of doctor conducting patient education and formulation on a daily basis, learning a basic way of thinking when clinical decisions are made for a patient nearby, mature decision making by combining vital signs, communication that takes into consideration a patient's background, and improved communication or problem-solving abilities within a broader team.

Rationale The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. Objectives To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Results Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Conclusions Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.