Enhanced memory and hippocampal connectivity in humans 2 days after brief resistance exercise.

INTRODUCTION: Exercise has significant health benefits and can enhance learning. A single bout of high-intensity resistance training may be sufficient to improve memory. This study aimed to assess memory enhancement by a single bout of high-intensity resistance training and to examine the neural underpinnings using resting-state functional magnetic resonance imaging (MRI). METHODS: Sixty young adults (34 men and 26 women), divided into the training and control groups, participated. The first session included verbal memory recall tests (cued- and free-recall), resting-state functional MRI (rs-fMRI), and a single-bout high-intensity resistance training for the training group. Two days later, they underwent post-intervention memory tests and rs-fMRI. The study design was 2 groups × 2 sessions for memory tests, and within training group comparisons for rs-fMRI. RESULTS: Compared to the control group without resistance training, the training group showed higher cued-recall performance 2 days after the brief resistance training (training: +0.27, control: -0.13, interaction: p = .01), and their free-recall scores were associated with enhanced left posterior hippocampal connectivity (r = .64, p < .001). CONCLUSIONS: These results suggest that brief high-intensity resistance exercise/strength training could enhance memory without repeated exercising. The quick effect of resistance training on memory and hippocampal connectivity could be revealed. A focused and one-shot exercise may be sufficient to enhance memory performance and neural plasticity in a few days.

Right amygdala and caudate activation patterns predict implicit attitudes toward people with autism spectrum disorders and physical disabilities, respectively.

Attitudes toward people with disabilities tend to be negative, regardless of the visibility of the disorder traits. Individuals with autism spectrum disorder (ASD) experience stigmatization that is rooted in negative attitudes or prejudice toward them because of their social awkwardness. The neural underpinnings of attitudes toward people with disabilities remain unclear. In this study, we focused on implicit attitudes toward people with ASD and physical disabilities, which are more visible than ASD, and investigated whether implicit attitudes were predicted by using neural activity with multivoxel pattern analysis (MVPA) in the prejudice network. Thirty-six, right-handed, Japanese, university students without disabilities participated. Two implicit association tests (IAT) toward people with ASD and physical disabilities revealed negative implicit attitudes. In the MRI scanner, participants performed a one-back task by using the same picture sets of IATs to examine their neural responses toward people with ASD and physical disabilities. According to the MVPA results, activation patterns of the right amygdala and right caudate significantly predicted implicit attitudes toward people with ASD and physical disabilities, respectively. These results suggest that implicit attitudes toward ASD and physical disabilities can be predicted by using neural signals from different regions within the prejudice network.

Academic achievements and brain volume development in children and adolescents.

Children are expected to acquire both basic and numeric skills. Achievement of higher levels of reading, writing, arithmetic, and vocabulary are favorable and desirable. The relationship between each literacy skill and neural development has been investigated; however, association between brain development and the 4 literacy skills has not been examined. This longitudinal, structural, neuroimaging study explored the contribution of higher academic achievement in reading, writing, arithmetic, and vocabulary to neural development. The brain volumes of children and adolescents aged 9-16 years were measured in the first test. Approximately 2.6 years later, the brain volumes and 4 academic achievement scores of 77 participants were measured in the second test. Changes in the gray matter volume in the left fusiform gyrus were associated with vocabulary scores, whereas those in the left striatum were associated with arithmetic scores. The reading and writing scores showed no statistically significant relationship with changes in brain volume. The current vocabulary score correlated with current gray matter volume, while brain volumes in the first test showed no association with any achievement scores. These results suggest that academic achievement may modulate brain plasticity in various ways.

Morphological comparison of masseter muscle fibres in the mandibular rest and open positions using diffusion tensor imaging.

BACKGROUND: The masseter muscle has a complicated multipennate internal structure and exhibits functional differentiation when performing various stomatognathic functions. It is important to understand the internal structural changes of the muscle during functioning to elucidate characteristic muscle disorders such as local myalgia. Diffusion tensor imaging (DTI) may be useful for investigating the internal structural features of muscle. OBJECTIVES: To evaluate the features of masseter muscle fibres in human participants using DTI fibre tractography, and to elucidate the structural differences in the masseter muscle between the mandibular rest and open positions. METHODS: Five healthy men (age 31 ± 7 years) underwent DTI and T1-weighted MRI of the right masseter muscle in the mandibular rest and open positions. MR images were used as a reference for muscle layer segmentation (superficial, intermediate, and deep). DTI fibre tractography of the masseter muscle was performed and the orientation of the DTI fibres was analysed in each layer using coordinates based on the Frankfurt horizontal plane. RESULTS: The DTI fibre orientation of the deep layer significantly changed between the mandibular rest and open positions in the frontal plane (p < 0.05, Wilcoxon rank sum test). However, no significant change was found in the superficial and intermediate layers. CONCLUSION: DTI fibre tractography confirmed regional differences in the orientation change of the masseter muscle fibres between different mandibular positions. The results may support the existence of functional partitioning inside the masseter muscle and suggest that DTI may be useful for the evaluation of muscle fibres in multipennate muscles.

Safety and effectiveness of ferric citrate hydrate in serum phosphorus management of patients with chronic kidney disease: a long-term, real-world, observational, post-marketing surveillance study.

BACKGROUND: Ferric citrate hydrate (FC) is an oral iron-based phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease (CKD). This post-marketing surveillance study was performed to investigate the long-term safety and effectiveness of FC. METHODS: This prospective, multicenter, observational post-marketing surveillance study was performed in a real-world setting in Japan. The study involved CKD patients with hyperphosphatemia receiving FC who were undergoing either hemodialysis or peritoneal dialysis or were non-dialysis-dependent. Adverse drug reactions, iron- and erythrocyte-related parameters (i.e., levels of serum ferritin, transferrin saturation, and hemoglobin), and serum levels of phosphorus, corrected calcium, and intact parathyroid hormone were monitored for up to 104 weeks. RESULTS: Safety was evaluated in 2723 patients. Of these patients, 20.5% discontinued FC because of adverse events, and 3.9% discontinued FC because of unsatisfactory effectiveness. Iron-related parameters gradually increased after the initiation of FC treatment but stabilized after week 36. Effectiveness was analyzed in 2367 patients. Serum phosphorus immediately decreased, and the effect persisted for 104 weeks. CONCLUSION: In this 104 week surveillance study, no new safety concerns were noted. The safety profile was not obviously different from those in pre-approval clinical trials and the 52 week interim report of this surveillance study. The serum ferritin level of most patients was below the upper limit of the target range, and iron overload risk was not evident. Long-term FC treatment effectively controlled serum phosphorus.

Application of Diffusion Tensor Imaging Fiber Tractography for Human Masseter Muscle.

Diffusion tensor imaging (DTI) has been used to indicate the direction of nerve and muscle fibers by using the characteristics that water molecules preferentially diffuse along the fibrous structure. However, DTI fiber tractography for multipennate muscles, such as the masseter muscle, is challenging due to a lack of data regarding the imaging parameters. This study aimed to determine the optimal DTI parameters for masseter muscle fiber tractography. A 27-year-old healthy man voluntarily underwent DTI and T1-weighted magnetic resonance imaging of the right masseter muscle. Four imaging parameter settings were created by combining the following parameters that particularly affect the signal-to-noise ratio: b-value, number of excitations (NEX), and number of motion probing gradient (MPG) directions. DTI fiber tractography was performed using specific software for each parameter setting. The length and orientation of the muscle fibers in each layer were calculated. As a result, the masseter muscle fibers of each layer were identified on DTI. Although the detected fiber length was affected significantly by the imaging parameters, the fiber orientation was insignificantly affected. The appropriate combination of the b-value, NEX, and the number of MPG directions for masseter muscle fiber tractography could be determined based on previously reported anatomical data of the masseter muscle fibers. DTI may enable the non-invasive evaluation of masseter muscle fiber length and orientation. Elucidation of the details of masseter muscle fiber orientation is useful in evaluating stomatognathic biomechanics and muscle disorders.

Interfacial ferroelectricity in marginally twisted 2D semiconductors.

Twisted heterostructures of two-dimensional crystals offer almost unlimited scope for the design of new metamaterials. Here we demonstrate a room temperature ferroelectric semiconductor that is assembled using mono- or few-layer MoS2. These van der Waals heterostructures feature broken inversion symmetry, which, together with the asymmetry of atomic arrangement at the interface of two 2D crystals, enables ferroelectric domains with alternating out-of-plane polarization arranged into a twist-controlled network. The last can be moved by applying out-of-plane electrical fields, as visualized in situ using channelling contrast electron microscopy. The observed interfacial charge transfer, movement of domain walls and their bending rigidity agree well with theoretical calculations. Furthermore, we demonstrate proof-of-principle field-effect transistors, where the channel resistance exhibits a pronounced hysteresis governed by pinning of ferroelectric domain walls. Our results show a potential avenue towards room temperature electronic and optoelectronic semiconductor devices with built-in ferroelectric memory functions.

Ultra-Structural Imaging Provides 3D Organization of 46 Chromosomes of a Human Lymphocyte Prophase Nucleus.

Three dimensional (3D) ultra-structural imaging is an important tool for unraveling the organizational structure of individual chromosomes at various stages of the cell cycle. Performing hitherto uninvestigated ultra-structural analysis of the human genome at prophase, we used serial block-face scanning electron microscopy (SBFSEM) to understand chromosomal architectural organization within 3D nuclear space. Acquired images allowed us to segment, reconstruct, and extract quantitative 3D structural information about the prophase nucleus and the preserved, intact individual chromosomes within it. Our data demonstrate that each chromosome can be identified with its homolog and classified into respective cytogenetic groups. Thereby, we present the first 3D karyotype built from the compact axial structure seen on the core of all prophase chromosomes. The chromosomes display parallel-aligned sister chromatids with familiar chromosome morphologies with no crossovers. Furthermore, the spatial positions of all 46 chromosomes revealed a pattern showing a gene density-based correlation and a neighborhood map of individual chromosomes based on their relative spatial positioning. A comprehensive picture of 3D chromosomal organization at the nanometer level in a single human lymphocyte cell is presented.

Intrinsic hippocampal functional connectivity underlying rigid memory in children and adolescents with autism spectrum disorder: A case-control study.

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.

Long-Term Safety and Effectiveness of the Xanthine Oxidoreductase Inhibitor, Topiroxostat in Japanese Hyperuricemic Patients with or Without Gout: A 54-week Open-label, Multicenter, Post-marketing Observational Study.

BACKGROUND AND OBJECTIVES: Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used for the management of hyperuricemic patients with or without gout in Japan. Accumulating evidence has demonstrated the efficacy of topiroxostat for the treatment of hyperuricemia with or without gout. However, the safety and efficacy of topiroxostat in the clinical setting remain unclear, and there is little large-scale clinical evidence. We conducted a post-marketing observational study over 54 weeks. PATIENTS AND METHODS: Patients were centrally enrolled, and case report forms of 4491 patients were collected between April 2014 and March 2019 from 825 medical sites. RESULTS: Overall, 4329 patients were assessed for safety and 4253 patients for effectiveness. The overall incidence of adverse drug reactions was 6.95%, and the incidence rates of adverse drug reactions of gouty arthritis, hepatic dysfunction, and skin disorders, which are of special interest in this study, were 0.79%, 1.73%, and 0.95%, respectively. No case of serious gouty arthritis was observed. Serum urate levels decreased stably over time and showed a significant reduction rate at 54 weeks (21.19% ± 22.07%) and on the final visit (19.91% ± 23.35%) compared to the baseline. The rates for subjects who achieved serum uric acid levels ≤ 6.0 mg/dL at 18 and 54 weeks after administration were 43.80% and 48.28%, respectively. CONCLUSIONS: This study suggests that there is no particular concern about adverse drug reactions or the efficacy of topiroxostat for hyperuricemic patients with or without gout in a post-marketing setting in Japan.

Association Between Resting-State Functional Connectivity and Reading in Two Writing Systems in Japanese Children With and Without Developmental Dyslexia.

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.

Neural mechanisms underlying concurrent listening of simultaneous speech.

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.

Investigation of Three-Dimensional Structure and Pigment Surrounding Environment of a TiO2 Containing Waterborne Paint.

Serial block-face scanning electron microscopy (SBFSEM) has been used to investigate the three-dimensional (3D) structure of a cured waterborne paint containing TiO2 pigment particles, and the surrounding environment of the TiO2 pigment particles in the cured paint film was also discussed. The 3D spatial distribution of the particles in the paint film and their degree of dispersion were clearly revealed. More than 55% of the measured TiO2 particles have volumes between 1.0 × 106 nm³ and 1.0 × 107 nm³. From the obtained 3D images, we proposed that there are three different types of voids in the measured cured waterborne paint film: voids that exist in the cured paint themselves, voids produced by particle shedding, and voids produced by quasi-liquid phase evaporation during measurement. Among these, the latter two types of voids are artefacts caused during SBFSEM measurement which provide evidence to support that the pigment particles in the cured paint/coating films are surrounding by quasi-liquid environment rather than dry solid environment. The error caused by particle shedding to the statistical calculation of the TiO2 particles was corrected in our analysis. The resulting 3D structure of the paint, especially the different voids are important for further systematic research, and are critical for understanding the real environment of the pigment particles in the cured paint films.

Atomic-Scale Insights into the Oxidation of Aluminum.

The surface oxidation of aluminum is still poorly understood despite its vital role as an insulator in electronics, in aluminum-air batteries, and in protecting the metal against corrosion. Here we use atomic resolution imaging in an environmental transmission electron microscope (TEM) to investigate the mechanism of aluminum oxide formation. Harnessing electron beam sputtering we prepare a pristine, oxide-free metal surface in the TEM. This allows us to study, as a function of crystallographic orientation and oxygen gas pressure, the full oxide growth regime from the first oxide nucleation to a complete saturated, few-nanometers-thick surface film.

Neural correlates of ambient thermal sensation: An fMRI study.

An increasing number of biometeorological and psychological studies have demonstrated the importance and complexity of the processes involved in environmental thermal perception in humans. However, extant functional imaging data on thermal perception have yet to fully reveal the neural mechanisms underlying these processes because most studies were performed using local thermal stimulation and did not dissociate thermal sensation from comfort. Thus, for the first time, the present study employed functional magnetic resonance imaging (fMRI) and manipulated ambient temperature during brain measurement to independently explore the neural correlates of thermal sensation and comfort. There were significant correlations between the sensation of a lower temperature and activation in the left dorsal posterior insula, putamen, amygdala, and bilateral retrosplenial cortices but no significant correlations were observed between brain activation and thermal comfort. The dorsal posterior insula corresponds to the phylogenetically new thermosensory cortex whereas the limbic structures (i.e., amygdala and retrosplenial cortex) and dorsal striatum may be associated with supramodal emotional representations and the behavioral motivation to obtain heat, respectively. The co-involvement of these phylogenetically new and old systems may explain the psychological processes underlying the flexible psychological and behavioral thermo-environmental adaptations that are unique to humans.

Three-dimensional positioning and structure of chromosomes in a human prophase nucleus.

The human genetic material is packaged into 46 chromosomes. The structure of chromosomes is known at the lowest level, where the DNA chain is wrapped around a core of eight histone proteins to form nucleosomes. Around a million of these nucleosomes, each about 11 nm in diameter and 6 nm in thickness, are wrapped up into the complex organelle of the chromosome, whose structure is mostly known at the level of visible light microscopy to form a characteristic cross shape in metaphase. However, the higher-order structure of human chromosomes, between a few tens and hundreds of nanometers, has not been well understood. We show a three-dimensional (3D) image of a human prophase nucleus obtained by serial block-face scanning electron microscopy, with 36 of the complete set of 46 chromosomes captured within it. The acquired image allows us to extract quantitative 3D structural information about the nucleus and the preserved, intact individual chromosomes within it, including their positioning and full spatial morphology at a resolution of around 50 nm in three dimensions. The chromosome positions were found, at least partially, to follow the pattern of chromosome territories previously observed only in interphase. The 3D conformation shows parallel, planar alignment of the chromatids, whose occupied volumes are almost fully accounted for by the DNA and known chromosomal proteins. We also propose a potential new method of identifying human chromosomes in three dimensions, on the basis of the measurements of their 3D morphology.

Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats.

There is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 µm) and long (L-AgNWs; 10 µm) nanowires instilled into the lungs of Sprague-Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health.

Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents.

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.

3D imaging by serial block face scanning electron microscopy for materials science using ultramicrotomy.

Mechanical serial block face scanning electron microscopy (SBFSEM) has emerged as a means of obtaining three dimensional (3D) electron images over volumes much larger than possible by focused ion beam (FIB) serial sectioning and at higher spatial resolution than achievable with conventional X-ray computed tomography (CT). Such high resolution 3D electron images can be employed for precisely determining the shape, volume fraction, distribution and connectivity of important microstructural features. While soft (fixed or frozen) biological samples are particularly well suited for nanoscale sectioning using an ultramicrotome, the technique can also produce excellent 3D images at electron microscope resolution in a time and resource-efficient manner for engineering materials. Currently, a lack of appreciation of the capabilities of ultramicrotomy and the operational challenges associated with minimising artefacts for different materials is limiting its wider application to engineering materials. Consequently, this paper outlines the current state of the art for SBFSEM examining in detail how damage is introduced during slicing and highlighting strategies for minimising such damage. A particular focus of the study is the acquisition of 3D images for a variety of metallic and coated systems.

Effects of the BDNF Val66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents.

The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) is associated with psychiatric disorders and regional gray matter volume (rGMV) in adults. However, the relationship between BDNF and rGMV in children has not been clarified. In this 3-year cross-sectional/longitudinal (2 time points) study, we investigated the effects of BDNF genotypes on rGMV in 185 healthy Japanese children aged 5.7-18.4 using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analyses. We found that the volume of the right cuneus in Met homozygotes (Met/Met) was greater than in Val homozygotes (Val/Val) in both exams, and the left insula and left ventromedial prefrontal cortex volumes were greater in Val homozygotes versus Met homozygotes in Exam l. In addition, Met homozygous subjects exhibited higher processing speed in intelligence indices than Val homozygotes and Val/Met heterozygotes at both time points. Longitudinal analysis showed that the left temporoparietal junction volume of Val/Met heterozygotes increased more substantially over the 3-year study period than in Val homozygotes, and age-related changes were observed for the Val/Met genotype. Our findings suggest that the presence of 2 Met alleles may have a positive effect on rGMV at the developmental stages analyzed in this study.