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Synesthesia is a condition in which the perception of a stimulus in one modality automatically triggers a secondary sensation in another modality or processing stream. Our study focused on grapheme-color synesthesia, in which the visual perception of letters or numbers (graphemes) induces a specific color sensation (the synesthetic color). Grapheme-color synesthetes do not typically experience colors for novel graphemes. However, synesthetic colors associated with familiar graphemes can be transferred to graphemes learned later, even in adulthood. A previous study has shown that such a transfer can take place after only a 10-min writing exercise. In this study, we found that this immediate transfer occurs only when the synesthetic colors for familiar graphemes contribute to the discrimination of the graphemes to be learned. Synesthetes learned six novel graphemes, each of which was arbitrarily associated with one of six familiar graphemes. Half of the synesthetes were assigned to the heterogeneous condition, in which the synesthetic colors of one group of familiar graphemes were different from one another. The other half of the synesthetes were assigned to the homogeneous condition, in which the various colors of a whole group of familiar graphemes were categorically the same. After this learning session, less transfer of synesthetic colors to novel graphemes from the corresponding familiar graphemes occurred in the homogeneous condition than in the heterogeneous condition. These results support the view that synesthetic colors for graphemes may function as a grapheme acquisition aid.

Childhood is an extremely important time for neural development that has a critical role in human intelligence. Efficient information processing is crucial for higher intelligence, so the intra- or inter-hemispheric interaction is vital. However, the relationship between neuroanatomical connections and intelligence in typically developing children, as well as sex differences in this relationship, remains unknown.Participants were 253 typically developing children (121 boys and 132 girls) aged 5-18. We acquired diffusion tensor imaging data and intelligence using an age-appropriate version of the IQ test; Wechsler Intelligence Scale for Children (WISC) or Wechsler Adult Intelligence Scale (WAIS). We conducted whole-brain multiple regression analysis to investigate the association between fractional anisotropy (FA), which reflects white matter microstructural properties, and each composite score of IQ test (full-scale IQ, performance IQ, and verbal IQ).FA was positively correlated with full-scale IQ in bilateral inferior occipitofrontal fasciculus, genu, and splenium of corpus callosum (CC). FA in the right superior longitudinal fasciculus, bilateral inferior longitudinal fasciculus, and splenium of CC were also positively correlated with performance IQ. Furthermore, we found significant sex interaction between FA in the CC and verbal IQ. FA was positively correlated in boys, and negatively correlated in girls.Results suggest that efficient anatomical connectivity between parietal and frontal regions is crucial for children's intelligence. Moreover, inter-hemispheric connections play a critical role in verbal abilities in boys.

Aims To assess the pharmacokinetics/pharmacodynamics (PK/PD) of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor that increases urinary glucose excretion (UGE) and its major metabolite, dapagliflozin-3-O-glucuronide (D3OG), in Japanese patients with type 1 diabetes (T1D) and inadequate glycaemic control (HbA1c 7%-10%). Materials and methods Japanese patients (18-65 years) with inadequately controlled T1D were randomized 1:1:1 to dapagliflozin 5 mg, 10 mg or placebo (n = 14 each) once daily for 7 days, with adjustable insulin. The PK/PD characteristics of dapagliflozin and D3OG were assessed on Day 7. Patients underwent follow-up evaluation on Days 8 and 14. Adverse events (AEs), hypoglycaemic episodes and events of diabetic ketoacidosis (DKA) were recorded over the treatment and follow-up periods. Results A total of 42 randomized patients received dapagliflozin or placebo. PK variables increased in a dose-dependent manner. D3OG was generated rapidly, with a median time to maximum plasma concentration of 2.0 hours (1.0-3.0). The dapagliflozin dose-UGE relationship was attenuated, with larger insulin dose reductions than anticipated. Mean percent (standard error) changes in total daily insulin dose from baseline to Day 7 were - 36.86% (3.32), -39.13% (2.68) and - 4.97% (5.28) for dapagliflozin 5 mg and 10 mg and for placebo, respectively. No DKA was reported. AEs were consistent with the established dapagliflozin safety profile. There was no increase in hypoglycaemia. Conclusions The PK and safety profiles of dapagliflozin in Japanese patients with T1D were consistent with previous studies, but with an unanticipated attenuation of the PD dose-response measured as UGE.

Irony comprehension requires integration of social contextual information. Previous studies have investigated temporal aspects of irony processing and its neural substrates using psychological/electroencephalogram or functional magnetic resonance imaging methods, but have not clarified the temporospatial neural mechanisms of irony comprehension. Therefore, we used magnetoencephalography to investigate the neural generators of alpha-band (8-13Hz) event-related desynchronization (ERD) occurring from 600 to 900ms following the onset of a critical sentence at which social situational contexts activated ironic representation. We found that the right anterior temporal lobe, which is involved in processing social knowledge and evaluating others' intentions, exhibited stronger alpha ERD following an ironic statement than following a literal statement. We also found that alpha power in the left anterior temporal lobe correlated with the participants' communication abilities. These results elucidate the temporospatial neural mechanisms of language comprehension in social contexts, including non-literal processing.

Aims To evaluate the efficacy and safety of dapagliflozin as add-on to insulin in Japanese patients with type 2 diabetes. Materials and methods Insulin-treated Japanese patients were randomized to 5 mg dapagliflozin or placebo during a 16-week double-blind treatment period. Both groups then received dapagliflozin 5 or 10 mg (the dose was increased at or after week 24 if glycated haemoglobin [HbA1c] at the previous visit was >7.5%) during a 36-week open-label extension period. The exploratory efficacy endpoint was to assess the maintenance efficacy of 5/10 mg dapagliflozin + insulin over 52 weeks of treatment. Safety was assessed in terms of adverse events, laboratory variables and vital signs. Results The changes in HbA1c from baseline to weeks 16 and 52 were −0.62% and −0.74%, respectively, in the dapagliflozin group, vs −0.08% and −0.83%, respectively, in the placebo–dapagliflozin group. Body weight decreased at both time points in the dapagliflozin group and after switching to open-label dapagliflozin in the placebo–dapagliflozin group. The total insulin dose decreased slightly after starting dapagliflozin. Adverse events occurred in 82.9% and 71.7% of patients in the dapagliflozin and placebo–dapagliflozin groups, respectively. Hypoglycaemia occurred in 35.0% and 41.7% of patients in the dapagliflozin and placebo–dapagliflozin groups, respectively, but the incidence was not increased by use of dapagliflozin in either trial period. Genital/urinary tract infections, renal impairment/failure, volume depletion, fracture and hepatic disorders occurred in ≤5% of patients. Conclusion This trial showed that administration of dapagliflozin as an add-on to insulin therapy was effective, was well tolerated and had insulin-sparing effects in Japanese patients with type 2 diabetes.

Sound symbolism, which is the systematic and non-arbitrary link between a word and its meaning, has been suggested to bootstrap language acquisition in infants. However, it is unclear how sound symbolism is processed in the infants’ brain. To address this issue, we investigated the cortical response in 11-month-old infants in relation to sound-symbolic correspondences using near-infrared spectroscopy (NIRS). Two types of stimuli were presented: a novel visual stimulus (e.g., a round shape) followed by a novel auditory stimulus that either sound-symbolically matched (moma) or mismatched (kipi) the shape. We found a significant hemodynamic increase in the right temporal area, when the sound and the referent sound were symbolically matched, but this effect was limited to the moma stimulus. The anatomical locus corresponds to the right posterior superior temporal sulcus (rSTS), which is thought to process sound symbolism in adults. These findings suggest that prelinguistic infants have the biological basis to detect cross-modal correspondences between word sounds and visual referents.

Psychological studies showed the quantity of reading habit affects the development of their reading skills, various language skills, and knowledge. However, despite a vast amount of literature, the effects of reading habit on the development of white matter (WM) structures critical to language and reading processes have never been investigated. In this study, we used the fractional anisotropy (FA) measure of diffusion tensor imaging to measure WM microstructural properties and examined cross-sectional and longitudinal correlations between reading habit and FA of the WM bundles in a large sample of normal children. In both cross-sectional and longitudinal analyses, we found that greater strength of reading habit positively affected FA in the left arcuate fasciculus (AF), in the left inferior fronto-occipital fasciculus (IFOF), and in the left posterior corona radiata (PCR). Consistent with previous studies, we also confirmed the significance or a tendency for positive correlation between the strength of reading habit and the Verbal Comprehension score in cross-sectional and longitudinal analyses. These cross-sectional and longitudinal findings indicate that a healthy reading habit may be directly or indirectly associated with the advanced development of WM critical to reading and language processes. Future intervention studies are needed to determine the causal effects of reading habits on WM in normal children.

Introduction Dapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated. Materials and Methods This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate efficacy (at 16 weeks) and long-term safety (at 52 weeks) of dapagliflozin in addition to insulin therapy. The interim analysis was carried out at week 16 to assess the efficacy and safety profiles. The patients receiving insulin (n = 182) were randomized to either dapagliflozin 5 mg or a placebo at a 2:1 ratio. The primary efficacy end-point was the change in hemoglobin A1c (HbA1c) from baseline at week 16. Results Patients in the dapagliflozin group showed an adjusted decrease in HbA1c of −0.55% from baseline, whereas the placebo showed a marginal increase of 0.05%. The placebo-corrected mean change of HbA1c from baseline to week 16 in dapagliflozin was −0.60% (P < 0.0001). In addition, the placebo-corrected mean change of fasting plasma glucose and bodyweight from baseline to week 16 in the dapagliflozin group was −22.7 mg/dL (P < 0.0001) and −1.21 kg (P < 0.0001), respectively. The placebo-corrected mean daily insulin dose in the dapagliflozin group was numerically decreased (treatment difference: −0.72 IU/day; P = 0.0743). No major episodes or discontinuations as a result of hypoglycemia were reported during the study period. Conclusions Dapagliflozin used as add-on treatment to insulin therapy showed significantly greater reduction of HbA1c, fasting plasma glucose and bodyweight without severe hypoglycemia compared with the placebo at week 16. These results show the clinical benefit of prescribing dapagliflozin for Japanese patients with insufficient glycemic control even with insulin therapy.

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

The empathizing-systemizing model describes human cognitive style using empathizing (the drive to identify another's mental state and respond appropriately) and systemizing (the drive to assess or construct rule-based systems). 'Brain type' was envisioned to explain individual differences in cognitive style based on the discrepancy of the two drives. In this model, individuals with autism spectrum disorder (ASD), a neurodevelopmental disorder, have extremely stronger systemizing. Revealing the underlying mechanisms of individual differences in cognitive style might contribute to elucidation of the pathology of ASD. We used voxel-based morphometry to compare the brain structures among the brain types (those who have stronger empathizing, those who have equally stronger drive to both, and those who have stronger systemizing) in 207 healthy children (age range: 5-15). Results showed that children with stronger systemizing had significantly greater grey matter volume of the right superior temporal gyrus (rSTG) than the others. The brain region, a distinctive brain structure of those with stronger systemizing, was overlapped with that of children with ASD. The rSTG is involved in detailed perceptual processing in social cognition, which is partially related to stronger systemizing. Our results contribute to elucidation of the underlying mechanisms of individual differences in cognitive style.

Excessive internet use is shown to be cross sectionally associated with lower cognitive functioning and reduced volume of several brain areas. However, the effects of daily internet use on the development of verbal intelligence and brain structures have not been investigated. Here, we cross sectionally examined the effects of the frequency of internet use on regional gray/white matter volume (rGMV/rWMV) and verbal intelligence as well as their longitudinal changes after 3.0 ± 0.3 (standard deviation) years in a large sample of children recruited from the general population (mean age, 11.2 ± 3.1 years; range, 5.7-18.4 years). Although there were no significant associations in cross sectional analyses, a higher frequency of internet use was found to be associated with decrease of verbal intelligence and smaller increase in rGMV and rWMV of widespread brain areas after a few years in longitudinal analyses. These areas involve areas related to language processing, attention and executive functions, emotion, and reward. In conclusion, frequent internet use is directly or indirectly associated with decrease of verbal intelligence and development to smaller gray matter volume at later stages.

A 74-year-old man with a history of occupational asbestos exposure in a shipyard was diagnosed with lymphohistiocytoid mesothelioma (LHM). Systemic chemotherapy consisted of cisplatin, and pemetrexed was administered. After six courses of chemotherapy, multiple tumours had regressed. Six months after chemotherapy, the tumours on the pleura exhibited regrowth and partly invaded the liver. Salvage chemotherapies, including irinotecan and vinorelbine, were administered and his disease was stable for several months. Then he suddenly vomited and complained of abdominal pain. Contrast CT showed small intestine intussusception. Partial resection of the small intestine was performed. We found a tumour in the resected small intestine. Review the …

The brain is a rare site of metastasis in malignant pleural mesothelioma (MPM), and its clinical features and prognosis remain unclear. The aim of this study was to investigate the incidence, prognosis, and risk factors for brain metastases (BM) in MPM patients. Between July 1993 and October 2014, 150 patients with histologically proven MPM were included in this retrospective study. The cumulative incidence of BM was estimated with the Kaplan-Meier method, and differences between groups were analyzed by the log-rank test. Multivariate logistic regression analysis was applied to assess risk factors for BM. The median follow-up time was 11 months (range 0-154.0 months). A total of eight patients (5.3 %) developed BM during the course of their illness. Multivariate analysis identified age

Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Several inflammation-based prognostic scores including the lymphocyte-to-monocyte ratio (LMR), Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) reportedly predict survival in many malignancies, while the role of LMR in MPM remains unclear. The aim of this study was to evaluate the clinical value of LMR and to compare the prognostic value of these inflammation-based scores in predicting overall survival (OS) in MPM.One hundred and fifty patients with histologically proven MPM were included in this retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for OS. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system.An elevated LMR was significantly associated with prolonged OS. Patients with LMR2.74 had significantly poor survival compared with LMR ≥2.74 (median, 5.0 versus 14.0 months; p=0.000). The LMR consistently had a higher AUC value at 6 months (0.722), 12 months (0.712), and 24 months (0.670), compared with other scores. Multivariate analysis showed that the LMR was independently associated with OS.The LMR is an independent prognostic marker for OS in patients with MPM and is superior to other inflammation-based prognostic scores with respect to prognostic ability.

We investigated cultural differences between U.S. and Japanese color preferences and the ecological factors that might influence them. Japanese and U.S. color preferences have both similarities (e.g., peaks around blue, troughs around dark-yellow, and preferences for saturated colors) and differences (Japanese participants like darker colors less than U.S. participants do). Complex gender differences were also evident that did not conform to previously reported effects. Palmer and Schloss's (2010) weighted affective valence estimate (WAVE) procedure was used to test the Ecological Valence Theory's (EVT's) prediction that within-culture WAVE-preference correlations should be higher than between-culture WAVE-preference correlations. The results supported several, but not all, predictions. In the second experiment, we tested color preferences of Japanese-U.S. multicultural participants who could read and speak both Japanese and English. Multicultural color preferences were intermediate between U.S. and Japanese preferences, consistent with the hypothesis that culturally specific personal experiences during one's lifetime influence color preferences.

Highlights • We investigated the relationship between cognitive pattern and gray matter volume. • Cognitive patterns were classified into 6 subtypes. • Volume of right middle temporal gyrus was differentiated by cognitive patters., Individual differences in cognitive patterning is informative in understanding one's cognitive strengths and weaknesses. However, little is known about the difference in brain structures relating to individual differences in cognitive patterning. In this study, we classified typically developing children (n = 277; age range, 5–16 years) into subtypes with k-means cluster analysis along with factor index scores using the Wechsler Intelligence Scale for Children (Third Edition). We then applied voxel-based morphometry to investigate whether significant gray-matter-volume differences existed among subtypes of cognitive patterns. Depending on the level of performance and cognitive patterning, we obtained six subtypes. One subtype that generally scored below average showed larger volume in the right middle temporal gyrus than the other five. On the other hand, two subtypes that achieved average levels of performance showed reverse-patterned factor index scores (one scored higher in Verbal Comprehension and Freedom from Distractibility, and the other scored lower in these two factor index scores) and had smaller volume in the right middle temporal gyrus than the other subtypes. From these results, we concluded that cognitive discrepancy was also obvious in typically developing children and that differences in cognitive patterning are represented in brain structure.

Humans perceive textual and nontextual information in visual perception, and both depend on language. In childhood education, students exhibit diverse perceptual abilities, such that some students process textual information better and some process nontextual information better. These predispositions involve many factors, including cognitive ability and learning preference. However, the relationship between verbal and nonverbal cognitive abilities and brain activation during visual perception has not yet been examined in children. We used functional magnetic resonance imaging to examine the relationship between nonverbal and verbal cognitive abilities and brain activation during nontextual visual perception in large numbers of children. A significant positive correlation was found between nonverbal cognitive abilities and brain activation in the right temporoparietal junction, which is thought to be related to attention reorienting. This significant positive correlation existed only in boys. These findings suggested that male brain activation differed from female brain activation, and that this depended on individual cognitive processes, even if there was no gender difference in behavioral performance.

One of the fundamental questions about grapheme–colour synaesthesia is how specific associations between the graphemes and colours are formed. We addressed this question by focusing on the determinants of synaesthetic colours for Japanese Kanji characters (logographic characters) using a psycholinguistic approach. Study 1 explored the influence meaning has on synaesthetic colours for Kanji characters representing abstract meanings by examining synaesthetic colours for antonym pairs (i.e. characters with meanings opposed to each other) in Japanese synaesthetes. Results showed that semantic relations influenced the grapheme–colour associations for characters representing abstract meanings in the early stages of learning abstract Kanji, while the influence was reduced in the grapheme–colour associations for those learned later. Study 2 examined the effect that learning new sounds or meanings of graphemes has on synaesthetic colours for those graphemes. Japanese synaesthetes were taught new sounds or new meanings for familiar Kanji characters. Results indicated that acquiring new information for graphemes slightly but significantly reduced the test–retest grapheme–colour association consistency, suggesting that synaesthetic colours can be modulated to reflect the synaesthete's latest knowledge about graphemes. Implications of these findings are discussed from the perspective of the relationship between synaesthesia and grapheme learning. This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.

We examined linear and curvilinear correlations of gray matter volume and density in cortical and subcortical gray matter with age using magnetic resonance images (MRI) in a large number of healthy children. We applied voxel‐based morphometry (VBM) and region‐of‐interest (ROI) analyses with the Akaike information criterion (AIC), which was used to determine the best‐fit model by selecting which predictor terms should be included. We collected data on brain structural MRI in 291 healthy children aged 5–18 years. Structural MRI data were segmented and normalized using a custom template by applying the diffeomorphic anatomical registration using exponentiated lie algebra (DARTEL) procedure. Next, we analyzed the correlations of gray matter volume and density with age in VBM with AIC by estimating linear, quadratic, and cubic polynomial functions. Several regions such as the prefrontal cortex, the precentral gyrus, and cerebellum showed significant linear or curvilinear correlations between gray matter volume and age on an increasing trajectory, and between gray matter density and age on a decreasing trajectory in VBM and ROI analyses with AIC. Because the trajectory of gray matter volume and density with age suggests the progress of brain maturation, our results may contribute to clarifying brain maturation in healthy children from the viewpoint of brain structure. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.

The Rapid Appearance and Disappearance of Dendriform Pulmonary Ossification after Diffuse Alveolar Hemorrhage Tomoko Yamagishi, Nobukazu Fujimoto, Yosuke Miyamoto, Naofumi Hara, Michiko Asano, Yasuko Fuchimoto, Sae Wada, Kenichi Kitamura, Shinji Ozaki, Hideyuki Nishi, and Takumi Kishimoto Department of Respiratory Medicine, Department of Medical Oncology, Department of Surgery, and Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan

There is a vast amount of evidence from psychological studies that the amount of parent–child interaction affects the development of children's verbal skills and knowledge. However, despite the vast amount of literature, brain structural development associated with the amount of parent–child interaction has never been investigated. In the present human study, we used voxel-based morphometry to measure regional gray matter density (rGMD) and examined cross-sectional correlations between the amount of time spent with parents and rGMD among 127 boys and 135 girls. We also assessed correlations between the amount of time spent with parents and longitudinal changes that occurred a few years later among 106 boys and 102 girls. After correcting for confounding factors, we found negative effects of spending time with parents on rGMD in areas in the bilateral superior temporal gyrus (STG) via cross-sectional analyses as well as in the contingent areas of the right STG. We also confirmed positive effects of spending time with parents on the Verbal Comprehension score in cross-sectional and longitudinal analyses. rGMD in partly overlapping or contingent areas of the right STG was negatively correlated with age and the Verbal Comprehension score in cross-sectional analyses. Subsequent analyses revealed verbal parent–child interactions have similar effects on Verbal Comprehension scores and rGMD in the right STG in both cross-sectional and longitudinal analyses. These findings indicate that parent–child interactions affect the right STG, which may be associated with verbal skills.

A 59-year-old man who was diagnosed with small cell lung cancer (SCLC), achieved a complete response to the induction chemoradiotherapy and received prophylactic cranial irradiation (PCI) (25 Gy at 250 cGy per fraction) in October 2008. Three months later, he complained of anorexia, weight loss, fatigue, and short-term memory loss and developed dementia and systemic muscle weakness. Magnetic resonance imaging in April and July 2009 revealed the progression of the diffuse brain atrophy without evidence of the metastasis of SCLC. Paraneoplastic neurological syndrome was suspected because anti-Hu antibody was detected in his serum and cerebrospinal fluid, but the adverse effects of chemotherapy and/or radiotherapy were also suspected as the cause of his neurological disorder.

People are generally lean during childhood and show more variability in body sizes and shapes later in life. Cortical development generally correlates with body growth. However, in children cortical growth may be impaired with oversized body growth. Inverse correlations between body mass index (BMI) and brain volumes suggest that lean bodies may be associated with increased cortical volume. To clarify the positive effects of a lean body on a child's cortical development, we used MRI to measure brain structures longitudinally in 107 children and adolescents aged 5-16 years. The relationships between changes in BMI and cortical volumes during 3 years of development were investigated, while controlling for age, gender and intracranial volume changes. Voxel-based morphometry analyses revealed that an increase in the volume of the right posterior medial temporal lobe - including the hippocampus and parahippocampal gyrus - was associated with lower BMI increases. No correlations were observed between higher BMI increases and cortical volumes. Our results suggest that keeping a lean body - or not getting fat - during childhood can induce an increase in regional cortical volume rather than impair growth. This is the first longitudinal study showing positive effects of a lean body on cortical development in children.

Television (TV) viewing is known to affect children's verbal abilities and other physical, cognitive, and emotional development in psychological studies. However, the brain structural development associated with TV viewing has never been investigated. Here we examined cross-sectional correlations between the duration of TV viewing and regional gray/white matter volume (rGMV/rWMV) among 133 boys and 143 girls as well as correlations between the duration of TV viewing and longitudinal changes that occurred a few years later among 111 boys and 105 girls. After correcting for confounding factors, we found positive effects of TV viewing on rGMV of the frontopolar and medial prefrontal areas in cross-sectional and longitudinal analyses, positive effects of TV viewing on rGMV/rWMV of areas of the visual cortex in cross-sectional analyses, and positive effects of TV viewing on rGMV of the hypothalamus/septum and sensorimotor areas in longitudinal analyses. We also confirmed negative effects of TV viewing on verbal intelligence quotient (IQ) in cross-sectional and longitudinal analyses. These anatomical correlates may be linked to previously known effects of TV viewing on verbal competence, aggression, and physical activity. In particular, the present results showed effects of TV viewing on the frontopolar area of the brain, which has been associated with intellectual abilities. Language: en

Introduction Like sleeping and eating habits, the study habits adopted by children when they are at home are important contributors to lifestyle and they affect cognitive ability. It has recently been reported that sleeping and eating habits change the brain structure of children. However, no research on the effect of study habits at home on the brain structure of children has been conducted thus far. We investigated the effects of study habits at home on the brain structures of healthy children by examining correlations between study time at home and changes in brain structure over the course of 3 years. Methods We used the brain magnetic resonance images of 229 healthy children aged 5.6–18.4 years and computed the changes (time 2–time 1) in regional gray matter and white matter volume (rWMV) using voxel-based morphometry. Whole-brain multiple regression analysis revealed a significant positive correlation between study time at home and changes in rWMV in the right superior frontal gyrus (SFG). Behaviorally, we found a significant positive correlation between study time at home and change in the verbal comprehension index (VCI), one of the subscales of the Wechsler Intelligence Scale for Children–third edition (WISC–III). Results and Conclusions Given that the SFG is involved in memory control and that the VCI measures abilities related to vocabulary, our results indicate that greater SFG involvement in the memorization component of longer study times may result in greater increases in the number of axons and more axon branching and myelination, causing plastic changes in the neural network involved in memory processes.

Using the eye-tracking method, the present study depicted pre- and post-head processing for simple scrambled sentences of head-final languages. Three versions of simple Japanese active sentences with ditransitive verbs were used: namely, (1) \(\text{ SO }_{\!1\!}\text{ O }_{\!2\!}\text{ V }\) canonical, (2) \(\text{ SO }_{\!2\!}\text{ O }_{\!1\!}\text{ V }\) single-scrambled, and (3) \(\text{ O }_{\!1\!}\text{ O }_{\!2\!}\text{ SV }\) double-scrambled order. First pass reading times indicated that the third noun phrase just before the verb in both single- and double-scrambled sentences required longer reading times compared to canonical sentences. Re-reading times (the sum of all fixations minus the first pass reading) showed that all noun phrases including the crucial phrase before the verb in double-scrambled sentences required longer re-reading times than those required for single-scrambled sentences; single-scrambled sentences had no difference from canonical ones. Therefore, a single filler-gap dependency can be resolved in pre-head anticipatory processing whereas two filler-gap dependencies require much greater cognitive loading than a single case. These two dependencies can be resolved in post-head processing using verb agreement information.

A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old). We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM) following magnetic resonance imaging (MRI). In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between a specific positive parenting behavior and brain structure in children.

Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6–18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech. Hum Brain Mapp 35:4079–4089, 2014. © 2014 Wiley Periodicals, Inc.

In this study, we examined linear and curvilinear correlations of fractional anisotropy (FA), mean diffusivity (MD), and white matter volume with age by using brain structural and diffusion‐tensor magnetic resonance imaging (MRI) in a large number of healthy children and voxel‐based morphometry (VBM) and region‐of‐interest (ROI) analyses. We collected data by brain structural MRI in 246 healthy children, aged 5–18 years. FA and MD images were normalized using the normalization parameter of the corresponding structural MRI. Next, we analyzed the correlations between FA and age and between MD and age by estimating linear and logarithmic functions. We also analyzed the correlation between white matter volume and age by linear, quadratic, and cubic functions. Correlations between FA and age and between MD and age showed exponential trajectories in most ROIs in boys and girls, except for several fibers, such as the corpus callosum connecting the bilateral rectal gyri in boys. The correlation between white matter volume and age showed significant positive linear trajectories in most ROIs in boys and girls, except for a few fibers, such as the bilateral uncinate fasciculus. Additionally, maturational rates differed among major fibers, and in girls, the left superior longitudinal fasciculus, which connects the frontal and temporal lobes, showed a slower rate of maturation than other fibers. Our results may help to clarify the mechanisms of normal brain maturation from the viewpoint of brain white matter. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.

A 62-year-old man with left chest pain had left pleural effusion pointed out on a chest radiograph. Chest CT scans showed multiple nodules on the left parietal pleura and pleural effusion. He was referred to our hospital and we performed thoracoscopic examination. Malignant pleural mesothelioma (biphasic type) was diagnosed, based on the pathological findings of a parietal nodular mass, including immunohistological analysis. Chemotherapy using carboplatin and pemetrexed reduced the size of tumor and left pleural effusion. This is a rare case with atypical CT findings of malignant pleural mesothelioma.

YOSHIDA, M. and ASANO, M. Direct Compression by Megadolichobasilar Anomaly as a Cause of Trigeminal Neuralgia, A Case Diagnosed by MRI. Tohoku J. Exp. Med., 1994, 172 (4), 327-332 A 49 year-old man with trigeminal neuralgia caused by megadolichobasilar anomaly was described. The patient having neuralgic attacks in the second branch of the right trigeminal nerve for two and a half years showed the angiographic evidence of a tortuous and elongated vertebrobasilar artery and MRI of the brain clearly visualized the root entry zone of the nerve having been compressed by the main trunk of ectatic basilar artery. Cases of trigeminal neuralgia due to the compression by the basilar artery itself have been rarely described previously. In order to evaluate trigeminal neuralgia, MRI is essential to determine the relationship of the involvedsite of nerve to the pathogenic artery.

The abilities to empathize and to systemize, two fundamental dimensions of cognitive style, are characterized by apparent individual differences. These abilities are typically measured using an empathizing quotient (EQ) and a systemizing quotient (SQ) questionnaire, respectively. The purpose of this study was to reveal any correlations between EQ and SQ scores and regional gray matter volumes in healthy children by applying voxel-based morphometry to magnetic resonance images. We collected MRIs of brain structure and administered children's versions of the EQ and SQ questionnaires (EQ-C and SQ-C, respectively) to 261 healthy children aged 5–15 years. Structural MRI data were segmented, normalized, and smoothed using an optimized voxel-based morphometric analysis. Next, we analyzed the correlation between regional gray matter volume and EQ-C and SQ-C scores adjusting for age, sex, and intracranial volume. The EQ-C scores showed significant positive correlations with the regional gray matter volumes of the left fronto-opercular and superior temporal cortices, including the precentral gyrus, the inferior frontal gyrus, the superior temporal gyrus, and the insula, which are functionally related to empathic processing. Additionally, SQ-C scores showed a significant negative correlation with the regional gray matter volume of the left posterior parietal cortex, which is functionally involved in selective attention processing. Our findings suggest that individual differences in cognitive style pertaining to empathizing or systemizing abilities could be explained by differences in the volume of brain structures that are functionally relevant to empathizing and systemizing.

Sleep is essential for living beings, and sleep loss has been shown to affect hippocampal structure and function in rats by inhibiting cell proliferation and neurogenesis in this region of the brain. We aimed to analyze the correlation between sleep duration and the hippocampal volume using brain magnetic resonance images of 290 healthy children aged 5-18 years. We examined the volume of gray matter, white matter, and the cerebrospinal fluid (CSF) space in the brain using a fully automated and established neuroimaging technique, voxel-based morphometry, which enabled global analysis of brain structure without bias towards any specific brain region while permitting the identification of potential differences or abnormalities in brain structures. We found that the regional gray matter volume of the bilateral hippocampal body was significantly positively correlated with sleep duration during weekdays after adjusting for age, sex, and intracranial volume. Our results indicated that sleep duration affects the hippocampal regional gray matter volume of healthy children. These findings advance our understanding of the importance of sleep habits in the daily lives of healthy children.

Two experiments explored rapid extraction of gist from a visual text and its influence on word recognition. In both, a short text (sentence) containing a target word was presented for 200 ms and was followed by a target recognition task. Results showed that participants recognized contextually anomalous word targets less frequently than contextually consistent counterparts (Experiment 1). This context effect was obtained when sentences contained the same semantic content but with disrupted syntactic structure (Experiment 2). Results demonstrate that words in a briefly presented visual sentence are processed in parallel and that rapid extraction of sentence gist relies on a primitive representation of sentence context (termed protocontext) that is semantically activated by the simultaneous presentation of multiple words (i.e., a sentence) before syntactic processing.

Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

To investigate gender differences in brain perfusion, this study utilized pulsed arterial spin-labeling magnetic resonance imaging (MRI) in a large number of healthy children. Data on structural and perfusion MRI in the brain were collected from 202 healthy children aged 5–18 years. Gender differences in brain perfusion using partial volume correction (PVC), which was calculated by dividing the normalized perfusion MRI by the normalized gray-matter segments, were analyzed by applying voxel-based analysis and region-of-interest (ROI) analysis. Girls showed significantly higher brain perfusion with PVC in the bilateral medial aspect of the parietal lobes, including the posterior cingulate cortex and precuneus, as compared to boys using voxel-based analysis. In addition, brain perfusion with PVC in the bilateral posterior cingulate cortex, bilateral precuneus, and left thalamus was significantly higher in girls than in boys in the ROI analysis. In contrast, no regions were seen in which boys exhibited higher brain perfusion with PVC than girls in both analyses. The findings showed significant differences between boys and girls in brain perfusion with PVC, and these differences may contribute to gender differences in the cognitive ability of healthy children.

We examined the correlation between brain perfusion and age using pulsed arterial spin‐labeling (ASL) magnetic resonance images (MRI) in a large number of healthy children. We collected data on brain structural and ASL perfusion MRI in 202 healthy children aged 5–18 years. Structural MRI data were segmented and normalized, applying a voxel‐based morphometric analysis. Perfusion MRI was normalized using the normalization parameter of the corresponding structural MRI. We calculated brain perfusion with an adjustment for gray matter density (BP‐GMD) by dividing normalized ASL MRI by normalized gray matter segments in 22 regions. Next, we analyzed the correlation between BP‐GMD and age in each region by estimating linear, quadratic, and cubic polynomial functions, using the Akaike information criterion. The correlation between BP‐GMD and age showed an inverted U shape followed by a U‐shaped trajectory in most regions. In addition, age at which BP‐GMD was highest was different among the lobes and gray matter regions, and the BP‐GMD association with age increased from the occipital to the frontal lobe via the temporal and parietal lobes. Our results indicate that higher order association cortices mature after the lower order cortices, and may help clarify the mechanisms of normal brain maturation from the viewpoint of brain perfusion. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.

The present study was performed to evaluate the effects of physical exercise at altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight subjects underwent intensive swimming training for 21 days at 1886 m. After altitude training commenced, red blood cell (RBC) counts and erythropoietin levels increased, but both haemoglobin and haematocrit levels did not change significantly. The serum level of VEGF, measured by means of a highly sensitive chemiluminescence (ELISA), showed a transient decrease 10 days after start of the altitude training, thereafter increasing significantly to reach a peak level 19 days later, rising from 23.0 +/- 5.3 to 46.0 +/- 14.6 pg mL-1 (P < 0.05 vs. before). On return to low altitude in Japan, the level of VEGF decreased, and 1 month later had returned to initial levels. Endurance training at altitudes increases serum VEGF levels; this could be an adaptive reaction to hypoxic conditions. This result suggests that VEGF may provide a new physiological parameter for hypoxic stress imposed by high altitude training.

The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using two-dimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P0.01) in the DPA and from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I2 derivatives.

The acute effects of beraprost sodium (sodium (±)-(1R ∗ , 2R, 3aS ∗ , 8bS ∗ )-2, 3, 3a 8b-tetrahydro-2-hydroxy-l-((E)-(3S ∗ )-3-hydroxy-4-methylI-octen-6-yny1] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I 2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner ® 40 μg) and elastase (Elaszym ® 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

The present study was undertaken to investigate the efficacy of a new, highly purified (purity greater than 91%), ethyl esterification product from natural eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis pedis artery using an ultrasonic color Doppler duplex system before and after oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross-sectional area of the dorsalis pedis artery increased significantly from 2.5 +/- 0.2 to 3.9 +/- 0.4 mm2 (48 weeks, mean +/- SE, p < 0.05). Moreover, EPA-E improved the clinical symptom (coldness, numbness) as well as the vibration perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/- 4.8 (48 weeks) microns]. A significant decrease of serum triglycerides was also noted by EPA-E administration. Furthermore, significant decrease of the excretion of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g.Cr, p < 0.05]. The results of this study suggest that EPA-E has significant beneficial effects on diabetic neuropathy and serum lipids as well as other diabetic complications such as nephropathy and macroangiopathy.

Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured. In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in amelio rating diabetic macroangiopathy and microangiopathy of the lower limbs.

A 67-year-old man with SIADH complicated by slowly progressing autonomic failure was described. The patient noticed constipation at the age of 57. In the following years, he suffered from urinary incontinence, depletion of sweating, impotence, sleeplessness with snore, and dizziness while walking. Physical examination revealed a masked oily face with slight cerebellar disturbance. Abnormality of autonomic function tests was recognized and he was diagnosed as Shy-Drager syndrome with gradually progressing, diffuse autonomic failure accompanied by slight cerebellar ataxia and Parkinsonism. Both serum sodium level and plasma osmotic pressure were reduced, whereas daily sodium excretion was more than 100mEq and urinary osmolality was about 500mOsm/kgH2O. His renal function was intact, and the adrenocortical and thyroid hormone levels were normal, then criteria of SIADH was fulfilled. SIADH was thought to have occurred on the basis of Shy-Drager syndrome. Water load test showed failure of adequate water diuresis, but intravenous phenytoin administration following the water load test ameliorated the diuresis to normal. The relationship between plasma osmolality and the ADH response indicates that ADH was adequately secreted in response to the increase in plasma osmolality but not suppressed in response to the decrease in plasma osmolality below 280mOsm/kgH2O. These results suggest that ADH synthesis in the hypothalamus and its secretion from the pituitary gland were both intact. The response of ADH secretion to the orthostatic hypotension induced by head-up tilt was quite blunted, being compatible with Shy-Drager Syndrome. Sleep disturbance was studied by polysomnography and laryngoscopy, and was revealed to be based upon severe sleep apnea due to incomplete paralysis of the bilateral vocal cords. Sleep apnea due to vocal cord paralysis is sometimes found to be complicated in patients with multiple system atrophy (MSA) including Shy-Drager syndrome, and is known as Gerhardt syndrome. This is the first report on a case of Shy-Drager syndrome complicated with SIADH and bilateral vocal cord paralysis. In this case, SIADH is caused by impaired afferent pathways from baroreceptors to the hypothalamus, which transfer inhibitory stimuli on ADH secretion. It is suggested that Shy-Drager syndrome should be considered one of the causes of SIADH.

A fundamental question in language development is how infants start to assign meaning to words. Here, using three Electroencephalogram (EEG)-based measures of brain activity, we establish that preverbal 11-month-old infants are sensitive to the non-arbitrary correspondences between language sounds and concepts, that is, to sound symbolism. In each trial, infant participants were presented with a visual stimulus (e.g., a round shape) followed by a novel spoken word that either sound-symbolically matched (“moma”) or mismatched (“kipi”) the shape. Amplitude increase in the gamma band showed perceptual integration of visual and auditory stimuli in the match condition within 300 msec of word onset. Furthermore, phase synchronization between electrodes at around 400 msec revealed intensified large-scale, left-hemispheric communication between brain regions in the mismatch condition as compared to the match condition, indicating heightened processing effort when integration was more demanding. Finally, event-related brain potentials showed an increased adult-like N400 response – an index of semantic integration difficulty – in the mismatch as compared to the match condition. Together, these findings suggest that 11-month-old infants spontaneously map auditory language onto visual experience by recruiting a cross-modal perceptual processing system and a nascent semantic network within the first year of life.