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Dipeptidyl peptidase IV inhibitor (DPP-4i) has been shown to act either as a promoter or as a suppressor for cancer. Although epidemiologic studies suggest that DPP-4i does not correlate with the development of malignancies, its effects on cancer metastases are controversial. We evaluated the impact of DPP-4i on postoperative outcomes of the diabetic patients with colorectal cancer and microscopic features of the resected tumors. In 260 consecutive patients with type 2 diabetes mellitus (T2DM) who underwent curative resection of colorectal cancer, the correlation between DPP-4i use and prognosis was retrospectively examined. Expression of Zeb1 on tumor cells and density of infiltrating immune cells were quantitatively evaluated with multicolor IHC in 40 tumors from DPP-4i users, 40 tumors from propensity score-matched users, and 40 tumors from nonusers. Postoperative disease-free survival (DFS) was significantly lower in 135 patients treated with DPP-4i compared with 125 nontreated patients [5-year DFS, 73.7% vs. 87.4%; HR, 1.98; 95% confidence interval (CI), 1.05-3.71; P = 0.035]. IHC revealed that the number of Zeb1 + tumor cells increased in tumors from DPP-4i-treated patients than tumors from nonusers ( P < 0.01). The densities of CD3 + and CD8 + T cells were significantly lower in tumors from DPP-4i users ( P < 0.01) with decreased density of tertiary lymphoid structures ( P < 0.001). However, the density of M2-type tumor-associated macrophages with CD68 + CD163 + phenotypes was significantly higher ( P < 0.01) in tumors from DPP-4i users. Exposure of colorectal cancer to DPP-4i may accelerate epithelial-to-mesenchymal transition (EMT) creating a tumor-permissive immune microenvironment, which might impair the outcomes of the patients with colorectal cancer and T2DM., Significance: DPP-4i has been shown to enhance the antitumor effects of immunotherapy. However, we found that DPP-4i significantly impairs the outcomes of patients with colorectal cancer who underwent curative resection, possibly through acceleration of EMT and creation of a tumor-permissive immune microenvironment. This suggests that DPP-4i must be used with caution until its safety is fully confirmed by further studies of the mechanistic effects on existing cancers in humans., Competing Interests: H. Yamaguchi reports grants from Taiho Pharmaceutical, Co., Ltd, Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., and grants from ONO Pharmaceutical Co., Ltd. outside the submitted work. No other disclosures were reported., (© 2021 The Authors; Published by the American Association for Cancer Research.)

The structural and functional brain characteristics associated with the excessive use of the internet have attracted substantial research attention in the past decade. In current study, we used voxel-based morphometry (VBM) and multiple regression analysis to assess the relationship between internet addiction tendency (IAT) score and regional gray and white matter volumes (rGMVs and rWMVs) and brain activity during a WM task in a large sample of healthy young adults (n = 1,154, mean age, 20.71 ± 1.78 years). We found a significant positive correlation between IAT score and gray matter volume (GMV) of right supramarginal gyrus (rSMG) and significant negative correlations with white matter volume (WMV) of right temporal lobe (sub-gyral and superior temporal gyrus), right sublobar area (extra-nuclear and lentiform nucleus), right cerebellar anterior lobe, cerebellar tonsil, right frontal lobe (inferior frontal gyrus and sub-gyral areas), and the pons. Also, IAT was significantly and positively correlated with brain activity in the default-mode network (DMN), medial frontal gyrus, medial part of the superior frontal gyrus, and anterior cingulate cortex during a 2-back working memory (WM) task. Moreover, whole-brain analyses of rGMV showed significant effects of interaction between sex and the IAT scores in the area spreading around the left anterior insula and left lentiform. This interaction was moderated by positive correlation in women. These results indicate that IAT is associated with (a) increased GMV in rSMG, which is involved in phonological processing, (b) decreased WMV in areas of frontal, sublobar, and temporal lobes, which are involved in response inhibition, and (c) reduced task-induced deactivation of the DMN, indicative of altered attentional allocation., Competing Interests: The authors declare no competing financial or non-financial interests.

Purpose: To determine the prognostic factors for success 3 years after Baerveldt glaucoma implant (BGI) surgery., Study Design: Single-center retrospective clinical study., Methods: We analyzed 27 eyes (24 patients) treated with BGI surgery between 2012 and 2016 at Osaka University Hospital. Patients were followed for a minimum of 3 years postoperatively. We analyzed the success rates and risk factors. Failure was defined as the need for additional surgery for IOP reduction, loss of light perception, and intraocular pressure (IOP) ≧22 mmHg (definition 1) or ≧17 mmHg (definition 2) at two consecutive follow-up visits., Results: The mean number of previous eye surgeries was 4.1 ± 3.3. The success rates were 81.5% and 77.8%, respectively, 1 year and 3 years after surgery based on definition 1 and 51.9% and 48.2%, respectively, based on definition 2. The early and late surgical complication rates, respectively, were 29.6% and 22.2%. An IOP 2 months after BGI surgery of ≧17 mmHg and the number of previous eye surgeries were significant risk factors for failure based on definition 2., Conclusion: The long-term results and complication rates after BGI surgery for refractory glaucoma in our hospital were similar to previous reports, and the IOP 2 months after BGI surgery and the number of previous eye surgeries were associated with the prognosis., (© 2021. Japanese Ophthalmological Society.)

Lay Abstract: Atypical learning and memory in early life can promote atypical behaviors in later life. Specifically, less relational learning and inflexible retrieval in childhood may enhance restricted and repeated behaviors in patients with autism spectrum disorder. The purpose of this study was to elucidate the mechanisms of atypical memory in children with autism spectrum disorder. We conducted picture-name pair learning and delayed-recognition tests with two groups of youths: one group with high-functioning autism spectrum disorder children (aged 7-16, n  = 41) and one group with typically developing children ( n  = 82) that matched the first group's age, sex, and full-scale IQ. We examined correlations between successful recognition scores and neural connectivity during resting in the magnetic resonance imaging scanner without thinking about anything. Although both learning and retrieval performances were comparable between the two groups, we observed significantly fewer memory gains in the autism spectrum disorder group than in the typically developing group. The memory network was involved in successful memory retrieval in youths with typically developing, while the other memory systems that do not depend to a great degree on networks may be involved in successful memory in youths with autism spectrum disorder. Context-independent and less relational memory processing may be associated with fewer memory gains in autism spectrum disorder. In other words, autism spectrum disorder youths might benefit from non-relational memory. These atypical memory characteristics in autism spectrum disorder may exaggerate their inflexible behaviors in some situations, or-vice versa-their atypical behaviors may result in rigid and less connected memories.

Objective: Although brain structural studies have demonstrated the neural correlates of neuroticism, the outcomes are not easily identified because of the various possible brain regions involved, low statistical power (low number of subjects), and brain structural measures available, such as mean diffusivity (MD), which are more suitable than standard regional measures of grey and white-matter volume (rGMV, rWMV) and fractional anisotropy (FA). We hypothesized that neuroticism neural correlates could be detected by MD and differentially identified using other measures. We aimed to visualize the neural correlates of neuroticism., Methods: A voxel-by-voxel regression analysis was performed using the MD, rGMV, rWMV, or FA value as the dependent variable and with neuroticism scores based on the NEO-FFI and its confounding factors as independent variables in 1207 (693 men and 514 women; age, 20.7 ± 1.8, 18-27 years), non-clinical students in a cross-sectional study., Results: MD in the cortico- (orbitofrontal cortex, anterior cingulate cortex, and posterior insula) striatal- (caudate and putamen) thalamic loop regions, including the right posterior limb of the internal capsule, were positively associated with neuroticism using the threshold-free cluster enhancement method with a family-wise error-corrected threshold of P < 0.0125 (0.05/4, Bonferroni correction for four types of MRI data [MD, rGMV, rWMV, and FA]) at the whole-brain level., Conclusions: An increased MD has generally been associated with reduced neural tissues and possibly area function. Accordingly, this finding helps elucidate the mechanism of somatization in neuroticism because the regions related to neuroticism are considered neural correlates of somatoform disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although it is known that health is not merely the absence of disease, the positive aspects of mental health have been less comprehensively researched compared with its negative aspects. Subjective well-being (SWB) is one of the indicators of positive psychology, and high SWB is considered to benefit individuals in multiple ways. However, the neural mechanisms underlying individual differences in SWB remain unclear, particularly in terms of brain microstructural properties as detected by diffusion tensor imaging. The present study aimed to investigate the relationship between measurements of diffusion tensor imaging [mean diffusivity (MD) and fractional anisotropy] and the degree of SWB as measured using a questionnaire. Voxel-based analysis was used to investigate the association between MD and SWB scores in healthy young adults (age, 20.7 ± 1.8 years; 695 males and 514 females). Higher levels of SWB were found to be associated with lower MD in areas surrounding the right putamen, insula, globus pallidus, thalamus and caudate. These results indicated that individual SWB is associated with variability in brain microstructural properties., (© The Author(s) 2021. Published by Oxford University Press.)

We report a case in which intraocular endoscopy clarified the cause of Ahmed glaucoma valve (AGV) failure with a cloudy cornea. A 42-year-old patient with glaucoma underwent AGV implant surgery to treat secondary glaucoma due to chronic iridocyclitis in his left eye. After AGV, he developed bullous keratopathy (BK) in that eye. After Descemet stripping automated endothelial keratoplasty (DSAEK) was performed to treat BK, the intraocular pressure (IOP) increased and early failure of the DSAEK resulted again in a cloudy cornea. We could not precisely detect any cause of AGV failure with ordinary imaging instrumentation. An intraocular endoscope was used to determine that cause, and we found that the fibrous tissue occluded the tube of the AGV. The IOP decreased soon after the tissue was removed. We conclude that intraocular endoscopy was useful for diagnosing AGV failure with BK., Competing Interests: The authors have no conflicts of interest to declare in this report., (Copyright © 2021 by S. Karger AG, Basel.)

Objective: To determine whether magnetoencephalography (MEG) can identify epileptiform discharges mimicking small sharp spikes (SSSs) on scalp electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE)., Methods: We retrospectively reviewed simultaneous scalp EEG and MEG recordings of 83 consecutive patients with TLE and 49 with extra-TLE (ETLE)., Results: SSSs in scalp EEG were detected in 15 (18.1%) of 83 TLE patients compared to only two (4.1%) of 49 ETLE patients (p = 0.029). Five of the 15 TLE patients had MEG spikes with concurrent SSSs in EEG, but neither of the 2 ETLE patients. Three of these 5 TLE patients had additional interictal epileptiform discharges (IEDs) in EEG and MEG. Equivalent current dipoles (ECDs) of MEG spikes with concurrent SSSs and IEDs showed no difference in temporal lobe localization and horizontal orientation, whereas ECD moments were smaller in MEG spikes with concurrent SSSs than those with IEDs., Conclusions: SSSs were more common in TLE than in ETLE. At least some morphologically diagnosed SSSs are true but low-amplitude epileptiform discharges in TLE which can be identified with simultaneous MEG., Significance: Simultaneous MEG is useful to identify epileptiform discharges mimicking SSSs in patients with TLE., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Lead is a toxin known to harm many organs in the body, particularly the central nervous system, across an individual's lifespan. To date, no study has yet investigated the associations between body lead level and the microstructural properties of gray matter areas, and brain activity during attention-demanding tasks. Here, utilizing data of diffusion tensor imaging, functional magnetic resonance imaging and cognitive measures among 920 typically developing young adults, we show greater hair lead levels are weakly but significantly associated with (a) increased working memory-related activity in the right premotor and pre-supplemental motor areas, (b) lower fractional anisotropy (FA) in white matter areas near the internal capsule, (c) lower mean diffusivity (MD) in the dopaminergic system in the left hemisphere and other widespread contingent areas, and (d) greater MD in the white matter area adjacent to the right fusiform gyrus. Higher lead levels were also weakly but significantly associated with lower performance in tests of high-order cognitive functions, such as the psychometric intelligence test, greater impulsivity measures, and higher novelty seeking and extraversion. These findings reflect the weak effect of daily lead level on the excitability and microstructural properties of the brain, particularly in the dopaminergic system., (© 2021. The Author(s).)

It is well known that physical exercise has beneficial effects on cognitive function in older adults. Recently, several physical exercise programs with virtual reality (VR) have been proposed to support physical exercise benefits. However, it is still unclear whether VR physical exercise (VR-PE) has positive effects on cognitive function in older adults. The purpose of this study was to conduct a systematic review (SR) of the effects of VR-PE on cognitive function in older adults with and without cognitive decline. We used academic databases to search for research papers. The criteria were intervention study using any VR-PE, participants were older adults with and without mild cognitive decline (not dementia), and cognitive functions were assessed. We found that 6 of 11 eligible studies reported the significant benefits of the VR-PE on a wide range of cognitive functions in aging populations. The SR revealed that VR-PE has beneficial effects on the inhibition of executive functions in older adults with and without mild cognitive decline. Moreover, VR-PE selectively leads to improvements in shifting and general cognitive performance in healthy older adults. The SR suggests that VR-PE could be a successful approach to improve cognitive function in older adults with and without cognitive decline.

This study aims to examine the neural mechanisms of resolving response competition during bilingual word recognition in the context of language intermixing. During fMRI scanning, Chinese-Japanese unbalanced bilinguals were required to perform a second-language (L2) lexical decision task composed of cognates, interlingual homographs, matched control words from both Chinese (first language) and Japanese (L2), and pseudowords. Cognate word processing showed longer reaction times and greater activation in the supplementary motor area (SMA) than L2 control word processing. In light of the orthographic and semantic overlap of cognates, these results reflect the cognitive processing involved in resolving response conflicts enhanced by the language membership of non-target language during bilingual word recognition. A significant effect of L2 proficiency was also observed only in the SMA, which is associated with the task decision system. This finding supports the bottom-up process in the BIA+ model and the Multilink model. The task/decision system receives the information from the word identification system, making appropriate responses during bilingual word recognition., 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 Hsieh, Jeong, Sugiura and Kawashima.)

Flow is a highly motivated and affectively positive state in which a person is deeply engaged in an activity and feeling enjoyment from it. In collaborative activities, it would be optimal if all participants were in a state of flow. However, flow states fluctuate amongst individuals due to differences in the dynamics of motivation and cognition. To explore the possibility that inter-brain synchronization can provide a quantitative measure of the convergence and divergence of collective motivational dynamics, we conducted a pilot study to investigate the relationship between inter-brain synchronization and the interpersonal similarity of flow state dynamics during the collaborative learning process. In two English as a Foreign Language (EFL) classes, students were divided into groups of three-four and seated at desks facing each other while conducting a 60-min group work. In both classes, two groups with four members were randomly selected, and their medial prefrontal neural activities were measured simultaneously using wireless functional near-infrared spectroscopy (fNIRS) devices. Later the participants observed their own activities on recorded videos and retrospectively rated their subjective degree of flow state on a seven-point scale for each 2-min period. For the pairs of students whose neural activities were measured, the similarity of their flow experience dynamics was evaluated by the temporal correlation between their flow ratings. Prefrontal inter-brain synchronization of the same student pairs during group work was evaluated using wavelet transform coherence. Statistical analyses revealed that: (1) flow dynamics were significantly more similar for the student pairs within the same group compared to the pairs of students assigned across different groups; (2) prefrontal inter-brain synchronization in the relatively short time scale (9.3-13.9 s) was significantly higher for the within-group pairs than for the cross-group pairs; and (3) the prefrontal inter-brain synchronization at the same short time scale was significantly and positively correlated with the similarity of flow dynamics, even after controlling for the effects of within- vs. cross-group pair types from the two variables. These suggest that inter-brain synchronization can indeed provide a quantitative measure for converging and diverging collective motivational dynamics during collaborative learning, with higher inter-brain synchronization corresponding to a more convergent flow experience., 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 Nozawa, Kondo, Yamamoto, Jeong, Ikeda, Sakaki, Miyake, Ishikawa and Kawashima.)

Shadowing and reading aloud both involve multiple complex cognitive processes, and both are considered effective methods for second-language learning. The working memory system, particularly the phonological loop, has been suggested to be involved in shadowing and reading aloud. The purpose of this study was to investigate the effects of a 4-week intensive adaptive training including shadowing and reading aloud of second language on working-memory capacity, regional gray matter volume (rGMV), and functional activation related to the n-back working-memory task in young adults. The results showed that compared with the training groups without speaking (listening to compressed speech and active control involving the second language), the training groups with speaking (shadowing and reading aloud) showed a tendency for greater test-retest increases in digit-span scores, and significantly greater test-retest decreases in N-back task reaction time (increase in working memory performance). Imaging analyses revealed compared with the active control group, shadowing group exhibited decreases in rGMV and brain activity during the working memory task (2-back task), in the left cerebellum and reading group exhibited decreases in them in the right anterior insula. These regions are parts of the phonological loop, suggesting the presence of training-induced neural plasticity in these neurocognitive mechanisms., (© 2020. The Author(s).)

We previously showed that the illusory sense of ownership and agency over a moving body in immersive virtual reality (displayed in a first-person perspective) can trigger subjective and physiological reactions on the real subject's body and, therefore, an acute improvement of cognitive functions after a single session of high-intensity intermittent exercise performed exclusively by one's own virtual body, similar to what happens when we actually do physical activity. As well as confirming previous results, here, we aimed at finding in the elderly an increased improvement after a longer virtual training with similar characteristics. Forty-two healthy older subjects (28 females, average age = 71.71 years) completed a parallel-group randomized controlled trial (RCT; UMIN000039843, umin.ac.jp) including an adapted version of the virtual training previously used: while sitting, participants observed the virtual body in a first-person perspective (1PP) or a third-person perspective (3PP) performing 20 min of virtual high-intensity intermittent exercise (vHIE; the avatar switched between fast and slow walking every 2 min). This was repeated twice a week for 6 weeks. During the vHIE, we measured the heart rate and administered questionnaires to evaluate illusory body ownership and agency. Before the beginning of the intervention, immediately after the first session of vHIE, and at the end of the entire intervention, we evaluated the cognitive performance at the Stroop task with online recording of the hemodynamic activity over the left dorsolateral prefrontal cortex. While we confirm previous results regarding the virtual illusion and its physiological effects, we did not find significant cognitive or neural improvement immediately after the first vHIE session. As a novelty, in the 1PP group only, we detected a significant decrease in the response time of the Stroop task in the post-intervention assessment compared to its baseline; coherently, we found an increased activation on left dorsolateral prefrontal cortex (lDLPFC) after the entire intervention. While the current results strengthen the impact of the virtual full-body illusion and its physiological consequences on the elderly as well, they might have stronger and more established body representations. Perhaps, a longer and increased exposure to those illusions is necessary to initiate the cascade of events that culminates to an improved cognitive performance., 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 Burin and Kawashima.)

A previous systematic review revealed that lutein intake leads to improved cognitive function among older adults. However, the association between lutein intake and brain health remains unclear., Methods: We searched the Web of Science, PubMed, PsycInfo, and Cochrane Library for research papers. The criteria were (1) an intervention study using oral lutein intake or a cross-sectional study that examined lutein levels and the brain, (2) participants were older adults, and (3) brain activities or structures were measured using a brain imaging technique (magnetic resonance imaging (MRI) or electroencephalography (EEG))., Results: Seven studies using MRI (brain activities during rest, cognitive tasks, and brain structure) and two studies using EEG were included. We mainly focused on MRI studies. Three intervention studies using MRI indicated that 10 mg lutein intake over 12 months had a positive impact on healthy older adults' brain activities during learning, resting-state connectivity, and gray matter volumes. Four cross-sectional studies using MRI suggested that lutein was positively associated with brain structure and neural efficiency during cognitive tasks., Conclusion: Although only nine studies that used similar datasets were reviewed, this systematic review indicates that lutein has beneficial effects on healthy older adults' brain health.

Childhood socioeconomic status is robustly associated with various children's cognitive factors and neural mechanisms. Here we show the association of childhood socioeconomic status with psychometric intelligence and mean diffusivity and fractional anisotropy using diffusion tensor imaging at the baseline experiment (N = 285) and longitudinal changes in these metrics after 3.0 ± 0.3 years (N = 223) in a large sample of normal Japanese children (mean age = 11.2 ± 3.1 years). After correcting for confounding factors, cross-sectional and longitudinal analyses show that higher childhood socioeconomic status is associated with greater baseline and baseline to follow-up increase of psychometric intelligence and mean diffusivity in areas around the bilateral fusiform gyrus. These results demonstrate that higher socioeconomic status is associated with higher psychometric intelligence measures and altered microstructural properties in the fusiform gyrus which plays a key role in reading and letter recognition and further augmentation of such tendencies during development. Definitive conclusions regarding the causality of these relationships requires intervention and physiological studies. However, the current findings should be considered when developing and revising policies regarding education.

Career choices affect not only our financial status but also our future well-being. When making these choices, individuals evaluate their willingness to obtain a job (i.e., job values), primarily driven by simulation of future pay and interest. Despite the importance of these decisions, their underlying neural mechanisms remain unclear. In this study, we examined the neural representation of pay and interest. Forty students were presented with 80 job names and asked to evaluate their job values while undergoing functional magnetic resonance imaging (fMRI). Following fMRI, participants rated the jobs in terms of pay and interest. The fMRI data revealed that the ventromedial prefrontal cortex (vmPFC) was associated with job value representation, and the ventral and dorsal regions of the posterior cingulate cortex (PCC) were associated with pay and interest representations, respectively. These findings suggest that the neural computations underlying job valuation conform to a multi-attribute decision-making framework, with overall value signals represented in the vmPFC and the attribute values (i.e., pay and interest) represented in specific regions outside the vmPFC, in the PCC. Furthermore, anatomically distinct representations of pay and interest in the PCC may reflect the differing roles of the two subregions in future simulations., (© The Author(s) 2021. Published by Oxford University Press.)

Recent evidence has indicated that the disruption of oligodendrocytes may be involved in the pathogenesis of depression. Genetic factors are likely to affect trait factors, such as characteristics, rather than state factors, such as depressive symptoms. Previously, a negative self-schema had been proposed as the major characteristic of constructing trait factors underlying susceptibility to depression. Thus, the association between a negative self-schema and the functional single nucleotide polymorphism (SNP) rs1059004 in the OLIG2 gene, which influences OLIG2 gene expression, white matter integrity, and cerebral blood flow, was evaluated. A total of 546 healthy subjects were subjected to genotype and psychological evaluation using the Beck Depression Inventory-II (BDI-II) and the Brief Core Schema Scale (BCSS). The rs1059004 SNP was found to be associated with the self-schema subscales of the BCSS and scores on the BDI-II in an allele dose-dependent manner, and to have a predictive impact on depressive symptoms via a negative-self schema. The results suggest the involvement of a genetic factor regulating oligodendrocyte function in generating a negative-self schema as a trait factor underlying susceptibility to depression., 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 Komatsu, Takeuchi, Ono, Yu, Kikuchi, Kakuto, Funakoshi, Ono, Kawashima, Taki and Tomita.)

This study tested the hypothesis that the magnitude of rectus femoris (RF) damage and the repeated bout effect (RBE) would be greater after knee extensor eccentric exercise performed in a supine (long RF lengths) than a sitting (short RF lengths) position, and the muscle length effects would be more prominent at the proximal than distal RF. Young untrained men were placed to one of the two groups (n = 14 per group). S group performed the knee extensor eccentric exercise in the sitting position for the first bout and the supine position for the second bout, and L group performed the exercise in the supine position for two bouts, with 4 weeks between bouts. Dependent variables included evoked and maximal voluntary isometric contraction (MVC) torque, electromyography (EMG) during MVC, muscle soreness, and shear modulus, which were measured before and 1-3 days after each exercise bout. After the first bout, L group in comparison with S group showed greater (P < .05) changes in hip flexor MVC torque (average of 1-3 days post-exercise: -11.1 ± 9.4% vs -5.0 ± 7.5%), proximal RF EMG (-22.4 ± 16% vs -9.0 ± 21.9%), and proximal RF shear modulus (33.2 ± 22.8% vs 16.9 ± 13.5%). No significant differences between groups were evident for any of other variables after the first bout including knee extensor MVC torque, and for the changes in all variables after the second bout. These results supported the hypothesis that RF damage would be greater for the spine than sitting position especially at the proximal region, but did not support the hypothesis about the RBE., (© 2020 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background/Purpose: Psychometric intelligence is closely related to working memory (WM) and the associated brain activity. We aimed to clarify the associations between psychometric intelligence and WM-induced functional connectivity changes. Materials and Methods: Here we determined the associations between psychometric intelligence measured by nonverbal reasoning (using the Raven's Advanced Progressive Matrices) and WM-induced changes in functional connectivity during the N-back paradigm, in a large cohort of 1221 young adults. Results: We observed that the measures of general intelligence showed a significant positive correlation with WM-induced changes in the functional connectivity with the key nodes of the frontoparietal network, such as the bilateral premotor cortices and the presupplementary motor area. Those significant correlations were observed for (1) areas showing a WM-induced increase of the functional connectivity with the abovementioned key nodes, such as the lateral parietal cortex; (2) areas showing a WM-induced decrease of the functional connectivity with the abovementioned key nodes (2-a) such as left perisylvian areas and cuneus, the fusiform gyrus, and the lingual gyrus, which play key roles in language processing, (2-b) hippocampus and parahippocampal gyrus, which play key roles in memory processing, and (2-c) the key node of the default mode network such as the medial prefrontal cortex; as well as (3) the border areas between (1) and (2). Conclusion: Psychometric intelligence is associated with WM-induced changes in functional connectivity, influencing the way in which WM key nodes dynamically modulate the interaction with other brain nodes in response to WM.

Purpose: Infrared monitor-guided bleb revision (IRGBR), an alternative needling system, visualizes anterior-segment tissues around the bleb not visible during needle revision after trabeculectomy. This study determined the safety and efficiency of 5-fluorouracil (5-FU) as an adjunctive anti-metabolite in IRGBR., Methods: We retrospectively analyzed 43 consecutive eyes (40 patients; 14 eyes, primary open-angle; 29 eyes, secondary glaucoma) treated with IRGBR for failing filtering blebs. The patients were divided into two groups. The first one had IRGBR without adjunctive 5-FU subconjunctival injection, and the second one had IRGBR with 5-FU. We performed Kaplan-Meier survival analysis using log-rank tests after 2 years of follow-up and Cox proportional hazards regression model to analyze the dependence of the survival time on predictor variables. Two failure criteria were defined as the need for additional surgery for intraocular pressure (IOP) reduction and the IOP at two consecutive follow-up visits based on definition 1, IOP ≧22 mmHg and definition 2, IOP ≧17 mmHg., Results: Thirty eyes (29 cases) underwent IRGBR with subconjunctival 5-FU injection (group A in the second term) and 13 eyes (11 cases) without 5-FU (group B in the first term). The success rates 24 months after IRGBR were 73.3 and 23.1%, respectively, in groups A and B based on the definition 1 failure and 56.7 and 7.7% based on the definition 2 failure. Complications included transient bleb leaks (group A, 3 eyes; group B, none) and choroidal detachment (group A, 1 eye; group B, none). No use of 5-FU and IOPs ≧10 mmHg 1 week after IRGBR were significant risk factors., Conclusions: Adjunctive 5-FU in IRGBR achieved a better success rate for failing trabeculectomy blebs.

Facing one's own death and managing the fear of death are important existential issues, particularly in older populations. Although recent functional magnetic resonance imaging (fMRI) studies have investigated brain responses to death-related stimuli, none has examined whether this brain activation was specific to one's own death or how it was related to dispositional fear of death. In this study, during fMRI, 34 elderly participants (aged, 60-72 years) were presented with either death-related or death-unrelated negative words and asked to evaluate the relevance of these words to the "self" or the "other." The results showed that only the left supplementary motor area (SMA) was selectively activated during self-relevant judgments of death-related words. Regression analyses of the effect of fear of death on brain activation during death-related thoughts identified a significant negative linear correlation in the right supramarginal gyrus (SMG) and an inverted-U-shaped correlation in the posterior cingulate cortex (PCC) only during self-relevant judgments. Our results suggest potential involvement of the SMA in the existential aspect of thoughts of death. The distinct fear-of-death-dependent responses in the SMG and PCC may reflect fear-associated distancing of the physical self and the processing of death-related thoughts as a self-relevant future agenda, respectively., (© The Author(s) 2021. Published by Oxford University Press.)

Epidemiological studies have reported that consumption of dairy products rich in β-lactolin is beneficial for cognitive decline among elderly individuals. Although previous studies have shown that β-lactolin supplementation improves memory function and attention in healthy adults, the mechanism through which β-lactolin affects human brain function has yet to be elucidated. This placebo-controlled randomized double-blind study therefore examined the effects of β-lactolin on human regional cerebral blood flow (rCBF) using near-infrared spectroscopy (NIRS) according to the Consolidated Standards of Reporting Trials guidelines. A total of 114 healthy participants aged between 50 and 75 years with relatively low cognition were randomly allocated into the β-lactolin or placebo groups ( n = 57 for both groups) and received supplementation for 6 weeks. After the 6 weeks of supplementation, total hemoglobin during cognitive tasks (Kraepelin and 2-back tasks) was measured using two-channel NIRS to determine rCBF. Accordingly, the β-lactolin group had significantly higher changes in total hemoglobin at the left dorsolateral prefrontal cortex (DLPFC) area measured using the left-side channel during the 2-back tasks ( p = 0.027) compared to the placebo group. The present study suggests that β-lactolin supplementation increases rCBF and DLPFC activity during working memory tasks.

Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older adults., Methods: In a 12-week double-blinded randomized control trial, 144 older adults were randomly assigned to one of four groups: BT with SFN (BT-S), BT with placebo (BT-P), active control game (AT) with SFN (AT-S), and active control game with placebo (AT-P). We used Brain Age in BT and Tetris in AT. Participants were asked to play BT or AT for 15 min a day for 12 weeks while taking a supplement (SFN or placebo). We measured several cognitive functions before and after the intervention period., Results: The BT (BT-S and BT-P) groups showed more improvement in processing speed than the active control groups (AT-S and AT-P). The SFN intake (BT-S and AT-S) groups recorded significant improvements in processing speed and working memory performance unlike the placebo intake groups (BT-P and AT-P). However, we did not find any evidence of the combined intervention's beneficial effects on cognition., Discussion: We discussed a mechanism to improve cognitive functions in the BT and SFN alone interventions.

The N100m response to a specific same-sound stimulus may be altered by the degree of attention paid to the stimulus. When participants selectively pay attention to the stimulus, the N100m amplitude increases; however, minimal effects are observed on the N100m latency. In this study, we examined the effects of selective special attention (motivation) to extract the frequency (or pitch) information from a probe tone on the N100m response to the probe tone. We compared the N100m latencies and amplitudes using magnetoencephalography, with the following three experimental conditions: 1) vocalization task protocol (vocalize in tune with the pitch of the probe tone after the presentation of the probe tone), 2) hearing task protocol (just listen to the probe tone), and 3) imagining (just imagine the vocalization in tune with the probe tone). The results indicated that the N100m latency in response to the probe tone was significantly shortened in the vocalization and imagining tasks compared with the hearing task in the right hemisphere of the brain. The amplitude was significantly increased in the vocalization task compared with the imagining and hearing tasks in the right hemisphere, and in the vocalization task compared with the hearing task in the left hemisphere of the brain; that is, the attention and/or motivation required to extract the information from the stimulus tones may have caused N100m latency shortening. To our knowledge, this study is the first to demonstrate that the N100m latency may be shortened under particular attentional conditions in response to a simple tone., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study explores neural mechanisms underlying how prior knowledge gained from pre-listening transcript reading helps comprehend fast-rate speech in a second language (L2) and applies to L2 learning. Top-down predictive processing by prior knowledge may play an important role in L2 speech comprehension and improving listening skill. By manipulating the pre-listening transcript effect (pre-listening transcript reading [TR] vs. no transcript reading [NTR]) and type of languages (first language (L1) vs. L2), we measured brain activity in L2 learners, who performed fast-rate listening comprehension tasks during functional magnetic resonance imaging. Thereafter, we examined whether TR&#95;L2-specific brain activity can predict individual learning success after an intensive listening training. The left angular and superior temporal gyri were key areas responsible for integrating prior knowledge to sensory input. Activity in these areas correlated significantly with gain scores on subsequent training, indicating that brain activity related to prior knowledge-sensory input integration predicts future learning success., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The APOE ɛ4 allele is associated with a risk of Alzheimer's disease in the elderly, with the association being pronounced in females. Conversely, findings of the effects of the APOE ɛ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ɛ4 allele on cognitive functions as well as brain structures among 1258 young adults. After adjusting for multiple comparisons, there were significant effects of the interaction between sex and the number of APOE ɛ4 allele on some speed tasks (e.g., simple processing speed tasks and the reverse Stroop task) as well as on regional white matter volume (rWMV). The observed sex-genotype interaction conferred better cognitive performance and greater rWMV in the anterior frontal and precentral white matter areas in females having more APOE ɛ4 alleles and reduced rWMV in the same areas in male having more APOE ɛ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ɛ4 allele in females., (© The Author(s) 2020. Published by Oxford University Press.)

Humans learn languages in real-life situations by integrating multiple signals, including linguistic forms, their meanings, and the actions and intentions of speakers. However, little is known about the neural bases underlying the social learning of a second language (L2) in adults. In this study, 36 adults were asked to learn two sets of L2 spoken words through translation versus simulated social interactive videos (social learning). Brain activation during word learning was measured using fMRI. Greater activation was observed in the bilateral superior temporal sulcus, posterior middle temporal gyri, and right inferior parietal lobule during social learning as compared with translation learning. Furthermore, higher activity in the right temporal parietal junction, right hippocampus, and motor areas was observed during the initial stage of social learning, with the more successful performance being at the time of overnight testing. We argue that social learning may strengthen the link from new L2 forms to rich L2 semantic representations wherein memory properties are embodied, multimodal, and richly contextualized., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies have indicated associations between several OLIG2 gene single-nucleotide polymorphisms (SNPs) and susceptibility to schizophrenia among Caucasians. Consistent with these findings, postmortem brain and diffusion tensor imaging studies have indicated that the schizophrenia-risk-associated allele (A) in the OLIG2 SNP rs1059004 predicts lower OLIG2 gene expression in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients and reduced white matter (WM) integrity of the corona radiata in normal brains among Caucasians. In an effort to replicate the association between this variant and WM integrity among healthy Japanese, we found that the number of A alleles was positively correlated with WM integrity in some fiber tracts, including the right posterior limb of the internal capsule, and with mean blood flow in a widespread area, including the inferior frontal operculum, orbital area, and triangular gyrus. Because the A allele affected WM integrity in opposite directions in Japanese and Caucasians, we investigated a possible association between the OLIG2 gene SNPs and the expression level of OLIG2 transcripts in postmortem DLPFCs. We evaluated rs1059004 and additional SNPs in the 5' upstream and 3' downstream regions of rs1059004 to cover the broader region of the OLIG2 gene. The 2 SNPs (rs1059004 and rs9653711) had opposite effects on OLIG2 gene expression in the DLPFC in Japanese and Caucasians. These findings suggest ethnicity-dependent opposite effects of OLIG2 gene SNPs on WM integrity and OLIG2 gene expression in the brain, which may partially explain the failures in replicating associations between genetic variants and psychiatric phenotypes among ethnicities., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Physical activity, such as high-intensity intermittent aerobic exercise (HIE), can improve executive functions. Although performing strength or aerobic training might be problematic or not feasible for someone. An experimental situation where there is no actual movement, but the body shows physiological reactions, is during the illusion through immersive virtual reality (IVR). We aimed to demonstrate whether a virtual HIE-based intervention (vHIE) performed exclusively by the own virtual body has physical, cognitive, and neural benefits on the real body. 45 healthy young adults (cross-over design) experienced HIE training in IVR (i.e., the virtual body performed eight sets of 30 s of running followed by 30 s of slow walking, while the subject is completely still) in two random-ordered conditions (administered in two sessions one week apart): the virtual body is displayed in first-person perspective (1PP) or third-person perspective (3PP). During the vHIE, we recorded the heart rate and subjective questionnaires to confirm the effectiveness of the illusion; before and after vHIE, we measured cortical hemodynamic changes in the participants' left dorsolateral prefrontal cortex (lDLPFC) using the fNIRS device during the Stroop task to test our main hypothesis. Preliminary, we confirmed that the illusion was effective: during the vHIE in 1PP, subjects' heart rate increased coherently with the virtual movements, and they reported subjective feelings of ownership and agency. Primarily, subjects were faster in executing the Stroop task after the vHIE in 1PP; also, the lDLPFC activity increased coherently. Clinically, these results might be exploited to train cognition and body simultaneously. Theoretically, we proved that the sense of body ownership and agency can affect other parameters, even in the absence of actual movements., (Copyright © 2020. Published by Elsevier Inc.)

Dysbiosis, an imbalance of intestinal flora, can cause serious conditions such as obesity, cancer, and psychoneurological disorders. One cause of dysbiosis is inflammation. Ulcerative enteritis is a side effect of non-steroidal anti-inflammatory drugs (NSAIDs). To counteract this side effect, we proposed the concurrent use of histamine H 2 receptor antagonists (H 2 RA), and we examined the effect on the intestinal flora. We generated a murine model of NSAID-induced intestinal mucosal injury, and we administered oral H 2 RA to the mice. We collected stool samples, compared the composition of intestinal flora using terminal restriction fragment length polymorphism, and performed organic acid analysis using high-performance liquid chromatography. The intestinal flora analysis revealed that NSAID [indomethacin (IDM)] administration increased Erysipelotrichacea e and decreased Clostridiales but that both had improved with the concurrent administration of H 2 RA. Fecal levels of acetic, propionic, and n-butyric acids increased with IDM administration and decreased with the concurrent administration of H 2 RA. Although in NSAID-induced gastroenteritis the proportion of intestinal microorganisms changes, leading to the deterioration of the intestinal environment, concurrent administration of H 2 RA can normalize the intestinal flora.

Neuropsychology and neuroimaging studies provide distinct views on the key neural underpinnings of social scene understanding (SSU): the amygdala and multimodal neocortical areas such as the posterior superior temporal sulcus (pSTS), respectively. This apparent incongruity may stem from the difference in the assumed cognitive processes of the situation-response association and the integrative or creative processing of social information. To examine the neural correlates of different SSU types using functional magnetic resonance imaging (fMRI), we devised a clothing recommendation task in three types of client's standpoint. Situation-response association was induced by a situation-congruent standpoint (ecological SSU), whereas the integrative and creative processing of social information was elicited by a lack and situation incongruence of the standpoint (perceptual and elaborative SSUs, respectively). Activation characteristic of the ecological SSU was identified in the right amygdala, while that of the perceptual SSU and elaborative SSU demand was identified in the right pSTS and left middle temporal gyrus (MTG), respectively. Thus, the current results provide evidence for the conceptual and neural distinction of the three types of SSU, with basic ecological SSU being supported by a limbic structure while sophisticated integrative or creative SSUs being developed in humans by multimodal association cortices.

The number of elderly individuals with age-related cognitive decline or dementia is rapidly increasing. Dairy product consumption, including β-lactolin, is beneficial for their cognitive function. The underlying mechanism of β-lactolin's effects on human brain activity is yet to be investigated. We examined the β-lactolin effects on human cerebral blood flow (CBF) using near-infrared spectroscopy (NIRS) in a placebo-controlled randomized double-blind study, which reported according to the CONSORT guidelines. Fifty healthy participants (aged 45-60 years) were randomly allocated into the β-lactolin or the placebo group (n = 25 each) and supplemented for 6 weeks. During the 6 th week, oxy-hemoglobin during the working memory tasks was measured using 34-channels (CHs) NIRS. The changes of oxy-hemoglobin, which represents the CBF, in CH 23 located at the left dorsolateral prefrontal cortex (DLPFC) during the spatial working memory task showed higher statistical significance (false discovery rate ( q ) = 0.045) in the β-lactolin than in the placebo group. The oxy-Hb changes in CH23 have a co-relationship with the working memory task reaction time. This clinical trial showed an increase in the CBF in the left DLPFC area during the 6-week β-lactolin supplementation. This study contributes to elucidating the underlying mechanisms of β-lactolin on cognitive performance.

Epilepsy is a network disease. The primary somatosensory cortex (S1) is usually considered to be intact, but could be subclinically disturbed based on abnormal functional connectivity in patients with temporal lobe epilepsy (TLE). We aimed to investigate if the S1 of TLE is abnormally modulated. Somatosensory evoked magnetic fields (SEFs) evoked by median nerve stimulation were recorded in each hemisphere of 15 TLE patients and 28 normal subjects. All responses were separately averaged in the awake state and light sleep using background magnetoencephalography. Latency and strength of the equivalent current dipole (ECD) was compared between the groups for the first (M1) and second peaks. Latencies showed no significant differences between the groups in either wakefulness or light sleep. ECD strengths were significantly lower in TLE patients than in controls only during wakefulness. The reduction of M1 ECD strength in the awake state is significantly correlated with duration of epilepsy. SEFs of TLE patients showed pure ECD strength reduction without latency delay. The phenomenon occurred exclusively during wakefulness, suggesting that a wakefulness-specific modulator of S1 is abnormal in TLE. Repetitive seizures may gradually insult the modulator of S1 distant from the epileptogenic network.

Background: Recent studies have demonstrated that brain activities using NIRS (near-infrared spectroscopy) at baseline during cognitive tasks (e.g., N-back task) can predict the cognitive benefits of a cognitive training. In this study, we investigated whether brain activities during brain training game (BT) at baseline would predict benefits to cognitive functions after the intervention period., Methods: In a four-week double-blinded randomized control trial (RCT) 72 young adults were randomly assigned to one of the two groups: participants in the BT group played specific game, called the Brain Age. Participants in an active control group (ACT) played the puzzle game Tetris. We measured brain activity during the training games using two channel NIRS before the intervention period. Cognitive functions were tested before and after the four-week intervention period., Results: The BT showed significant improvements in inhibition, processing speed, and working memory performance compared to ACT. The left and right DLPFC (dorsolateral prefrontal cortex) brain activities during the BT at baseline were associated with improvements in inhibition and processing speed., Discussion: This randomized control trial first provides scientific evidence that DLPFC activities during BT at baseline can predict cognitive improvements after a four-week intervention period.

The originality of creativity measured by divergent thinking (CMDT) is a unique variable that is positively correlated with psychometric intelligence and other psychological measures. Here, we aimed to determine the associations of CMDT originality/fluency scores and brain activity associated with working memory (WM) and simple cognitive processes during the N-back paradigm in a cohort of 1221 young adults. We observed that originality/fluency scores were associated with greater brain activity during the 0-back simple cognitive task and 2-back WM task in key nodes of the ventral attention system in the right hemisphere. Further, subjects with higher originality/fluency scores showed lower task-induced deactivations in areas of the default mode network, especially during the 2-back task. Psychological analyses revealed the associations of originality/fluency scores with both psychometric intelligence and systemizing. We also observed the effects of interaction between sex and originality/fluency scores on functional activity during the 0-back task in posterior parts of the default mode network together with other areas as well as simple processing speed. These results indicate that the originality of CMDT is associated with (a) greater activation of the ventral attention system, which is involved in reorienting attention and (b) reduced task-induced deactivation of the default mode network, which is indicative of alterations in attentional reallocation, and (c) cognitive correlates of originality of CMDT and revealed sex differences in these associations., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Japanese is unique, as it features two distinct writing systems that share the same sound and meaning: syllabic Hiragana and logographic Kanji scripts. Acquired reading difficulties in Hiragana and Kanji have been examined in older patients with brain lesions. However, the precise mechanisms underlying deficits in developmental dyslexia (DD) remain unclear. Materials and Methods: The neural signatures of Japanese children with DD were examined by using resting-state functional magnetic resonance imaging. We examined 22 dyslexic and 46 typically developing (TD) children, aged 7-14 years. Results: Reading performance in each writing system was correlated with neural connectivity in TD children. In contrast, in children with DD, weak associations between neural connectivity and reading performance were observed. In TD children, Hiragana-reading fluency was positively correlated with the left fusiform gyrus network. No significant correlations between Hiragana fluency and neural connectivity were observed in children with DD. Correspondingly, there were fewer correlations between Kanji accuracy and strength of reading-related connectivity in children with DD, whereas positive correlations with the bilateral fronto-parietal network and negative correlations with the left fusiform network were found in TD children. Discussion: These data suggest that positive and negative coupling with neural connectivity is associated with developing Japanese reading skills. Further, different neural connectivity correlations between Hiragana fluency and Kanji accuracy were detected in TD children but less in children with DD. Conclusion: The two writing systems may exert differential effects and deficits on reading in healthy children and in children with DD, respectively.

Obesity causes a wide range of systemic diseases and is associated with mood and anxiety disorders. It is also associated with dopaminergic reward system function. However, the relationships between microstructural properties of the dopaminergic system and body mass index (BMI) have not been investigated. In this study, we investigated the associations of BMI with mean diffusivity (MD), diffusion tensor imaging measure in areas of the dopaminergic system (MDDS) in 435 healthy young adults with mild obesity and without obesity (BMI < 40). We detected the association between greater BMI and lower MD of the right globus pallidus and the right putamen. These results suggest that the property of the dopaminergic system is associated with BMI among young adults with mild obesity and without obesity.

Zinc is a biologically essential element and involved in a wide range of cellular processes. Here, we investigated the associations of zinc levels in hair with brain activity during the n-back working memory task using functional magnetic resonance imaging, fractional anisotropy (FA) of diffusion tensor imaging, and cognitive differences in a study cohort of 924 healthy young adults. Our findings showed that greater hair zinc levels were associated with lower brain activity during working memory in extensive areas in the default mode network (i.e., greater task-induced deactivation) as well as greater FA in white matter areas near the hippocampus and posterior limbs of the internal capsule. These findings advance previous non-neuroimaging findings of zinc's associations with excitability, excitability-associated disorders, and myelination.

The presence of blood during ophthalmic surgery is problematic, as it can obstruct a surgeon's view of the operative field. This is particularly true when performing trabeculectomy surgery to enhance ocular fluid outflow and reduce intraocular pressure as a treatment for glaucoma, one of the most common vision loss conditions worldwide. In this study, we investigated the performance of a transparent, self-assembling peptide gel (SPG-178) and its ability to maintain visibility during trabeculectomy surgery. Unlike the hyaluronic acid gel commonly used in ophthalmic surgery, SPG-178 did not permit the ingress of blood into the gel itself. Rather, it forced blood to flow peripherally to the gel. Moreover, if bleeding occurred under the SPG-178 gel, perfusion with saline was able to effectively flush the blood away along the interface between the SPG-178 and the ocular tissue (in this case scleral) to clear the surgical field of view. In experimental trabeculectomy surgeries with mitomycin C used as an adjuvant, there were no differences in the postoperative recovery of intraocular pressure or bleb morphology with or without the use of SPG-178. SPG-178, therefore, when used in a gel formulation, represents a new material for use in intraocular surgery to ensure a clear operative field with likely beneficial treatment outcomes.

Maintaining emotional well-being in late life is crucial for achieving successful and healthy aging. While previous research from Western cultures has documented that emotional well-being improves as individuals get older, previous research provided mixed evidence on the effects of age on well-being in Eastern Asian cultures. However, previous studies in East Asia do not always take into account the effects of cognitive control-an ability which has been considered as a key to enable older adults to regulate their emotions. In the current study, we tested whether cognitive control abilities interact with age in determining individuals' well-being in 59 Japanese females (age range: 26-79; M age = 64.95). Participants' mental health and mental fatigue were tracked for 5 years together with their cognitive control abilities. We found that as individuals became older, they showed improved mental health and decreased mental fatigue. In addition, we found a quadratic effect of age on mental fatigue, which was further qualified by baseline cognitive control abilities. Specifically, in those who had a lower level of cognitive control abilities, mental fatigue declined until the mid-60s, at which point it started increasing (a U-shape effect). In contrast, in those who had a higher level of cognitive control ability, mental fatigue showed a steady decrease with age even after their mid-60s. These results suggest that whether advancing age is associated with positive vs. negative changes in well-being depends on cognitive control abilities, and that preserved cognitive control is a key to maintain well-being in late life., (Copyright © 2020 Yagi, Nouchi, Murayama, Sakaki and Kawashima.)

At 32 weeks of gestation, a male fetus with congenitally corrected transposition of the great arteries developed hydrops fetalis caused by a combination of mitral valve regurgitation and tricuspid valve regurgitation (TR). We performed a pulmonary artery banding (PAB) at 108 days old for gradually progressing TR, after confirming that a balloon dilatation test in the main pulmonary artery reduced TR. As the patient grew, the PAB became tighter and systolic blood pressure in the morphological left ventricle increased. At present, the patient is waiting for a double switch operation.

Background: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese., Methods: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis., Results: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P meta = .0019, OR = 4.55, I 2 = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P meta = .81, OR = 1.05; I 2 = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects., Conclusions: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

Can we identify what two people are saying at the same time? Although it is difficult to perfectly repeat two or more simultaneous messages, listeners can report information from both speakers. In a concurrent/divided listening task, enhanced attention and segregation of speech can be required rather than selection and suppression. However, the neural mechanisms of concurrent listening to multi-speaker concurrent speech has yet to be clarified. The present study utilized functional magnetic resonance imaging to examine the neural responses of healthy young adults listening to concurrent male and female speakers in an attempt to reveal the mechanism of concurrent listening. After practice and multiple trials testing concurrent listening, 31 participants achieved performance comparable with that of selective listening. Furthermore, compared to selective listening, concurrent listening induced greater activation in the anterior cingulate cortex, bilateral anterior insula, frontoparietal regions, and the periaqueductal gray region. In addition to the salience network for multi-speaker listening, attentional modulation and enhanced segregation of these signals could be used to achieve successful concurrent listening. These results indicate the presence of a potential mechanism by which one can listen to two voices with enhanced attention to saliency signals., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The needle revision procedure to address failing filtering blebs is a blind technique that might easily damage the scleral flap, conjunctiva, and choroid. We propose a new surgical procedure, infrared monitor-guided bleb revision, to perform bleb revision minimally invasively and effectively, and demonstrate the procedure in a patient. We developed the guided procedure with the infrared monitor to observe the bleb interior with greater contrast. Under the monitor, we dissect the hard fibrotic tissue with a bleb knife and, if necessary, remove adhesions using a needle and vitreous forceps. Finally, 5-fluorouracil is injected into the subconjunctiva. We have performed bleb revisions safely with clear visualization of the scleral flap using an infrared light. In the current case, the patient had good intraocular pressure control for about 1 year. The new infrared monitor-guided bleb revision procedure facilitates successful bleb revisions without damage to the underlying structures., Competing Interests: The authors have no conflicts of interest to declare in this report., (Copyright © 2020 by S. Karger AG, Basel.)

Background: Long-term combination of physical exercises has reported benefits for cognitive functions and mood states. However, it remains unclear whether a single bout of combination exercise training has acute positive effects on cognitive functions and mood states in middle-aged and older women. It is important to investigate acute effect of physical exercise because it would help to understand a mechanism of benefits of physical exercise. The purpose of this study was to investigate 30 min of a single bout of combination exercise training on cognition and mood states in middle-aged and older females., Methods: In this single-blinded randomized control trial (RCT), middle-aged and older females were assigned randomly to two groups: a combination exercise group and a no-exercise control group. The former group did the combination exercise training (aerobic, strength, and stretching exercises) for 30 min. Meanwhile, the latter group did not do any exercise and waited for 30 min. We measured cognitive functions and mood performance states before and after the exercise or control interventions., Results: Our main results demonstrated that, compared to the control group, the combination exercise improved inhibition (reverse Stroop and Stroop) and increased vigor-activity mood scores in both middle-aged and older groups. We also found that the only combination exercise group showed the significant positive correlations between improved inhibition performance and improved vigor-activity mood., Discussion: This randomized controlled trial revealed the acute benefits of combination exercise on inhibition in executive functions and vigor-activity in the healthy middle-aged and older females. Our results provided the scientific evidence related to acute effects of the single bout of the combination exercise training. It suggests that we would be better to do the 30 min physical exercise for our health., Clinical Trial Registration: This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000029681). Registered 24 October 2017, https://upload.umin.ac.jp/cgi-bin/ctr/ctr&#95;view&#95;reg.cgi?recptno=R000033922., (Copyright © 2020 Nouchi, Nouchi and Kawashima.)

Numerous studies have reported that the Met allele of the brain-derived neurotrophic factor (BDNF) gene polymorphism reduces neural plasticity. A reduction in mean diffusivity (MD) in diffusion tensor imaging (DTI) characteristically reflects the neural plasticity that involves increased tissue components. In this study, we revealed that the number of Met-BDNF alleles was negatively associated with MD throughout the whole-brain gray and white matter areas of 743 subjects using DTI and whole-brain multiple regression analyses. Within the same sample, the region of interest analysis revealed that the number of Met-BDNF alleles significantly and positively correlated with the mean FA value in the body of the corpus callosum. In addition, we observed interaction effects between BDNF Val66Met polymorphism and daily physical activity levels on MD, but not FA, in significant clusters of the bilateral hemisphere (n = 577 subjects). Post-hoc multiple regression analyses revealed that after correcting for confounding variables, there was a significant negative correlation between the physical activity level and mean MD of the whole brain in the Val/Val group [standardized partial regression coefficient (β) = -0.196, P = 0.005, t = -2.825], but not in the Val/Met (β = 0.050, P = 0.412, t = 0.822) and Met/Met groups (β = 0.092, P = 0.382, t = 0.878). These results underscore the importance of the interaction between physical activity and the BDNF Val66Met polymorphism, which affects the plasticity of neural mechanisms.

Critical thinking (CT) is important for consensus building. Although the practice of CT using debate is widely used to improve open-minded thought, the cognitive processes underlying this improvement remain poorly understood. Here, functional magnetic resonance imaging (fMRI) was employed to assess how neural responses while considering another's opinion are changed by CT practice and to determine whether the cortical network showing activation changes related to personality traits is relevant to consensus building. A total of 52 healthy participants were divided into three groups for an intervention; the participants read another's reasoning regarding a controversial issue and judged whether this person's viewpoint was affirmative during fMRI measurements. The intervention required them to prepare speech texts from a designated viewpoint based on both themselves and others. Compared to the control group, the group who took another's perspective showed enhanced activation of the right parieto-frontal network, that has been implicated in belief update, cognitive reappraisal of emotion, and self-perspective inhibition. Additionally, activation of the orbitofrontal cortex was negatively correlated with a stubbornness index. The results provide the first neural evidence of the effects of CT practice and support the notion that open-minded thought underlies the benefits of this practice.

The effectiveness of cognitive bias modification for interpretation (CBM-I), a treatment method employed to reduce social anxiety (SA), has been examined. However, the neural correlates of CBM-I remain unclear, and we aimed to elucidate brain activities during intervention and activity changes associated with CBM-I effectiveness in a pre-post intervention comparison. Healthy participants divided into two groups (CBM, control) were scanned before, during and after intervention using functional magnetic resonance imaging. Ambiguous social situations followed by positive outcomes were repeatedly imagined by the CBM group during intervention, while half of the outcomes in the control group were negative. Whole-brain analysis revealed that activation of the somatomotor and somatosensory areas, occipital lobe, fusiform gyrus and thalamus during intervention was significantly greater in the CBM than in the control group. Furthermore, altered activities in the somatomotor and somatosensory areas, occipital lobe and posterior cingulate gyrus during interpreting ambiguous social situations showed a significant group × change in SA interaction. Our result suggests that when facing ambiguous social situations, positive imagery instilled by CBM-I is recalled, and interpretations are modified to contain social reward. These findings may help to suggest an alternative manner of enhancing CBM-I effectiveness from a cognitive-neuroscience perspective., (© The Author(s) 2020. Published by Oxford University Press.)

In laboratory settings, creativity is measured using tasks of divergent as well as convergent thinking. It has been suggested that brain connectivity is important for creativity. In the present study, we investigated the associations of convergent thinking performance of compound Remote Associates Test (CRAT) with fractional anisotropy (FA) in diffusion tensor imaging and regional white matter (WM) volume (rWMV) in voxel-based morphometry in a large sample of healthy young adults (360 males and 280 females; mean age: 20.9 years, SD ​= ​1.6). We showed that CRAT performance was positively correlated with WM pathway property (i.e., FA) in the left fronto-occipital fasciculus and the left inferior longitudinal fasciculus, which play important roles in processing of language and concept. Further, CRAT performance was negatively correlated with rWMV in the widespread frontal temporal subcortical and cerebellar WM areas, suggesting the unique association of convergent thinking with WM connectivity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)