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.

Sex-Dependent Effects of the APOE ɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults.

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.

Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex.

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.

Originality of divergent thinking is associated with working memory-related brain activity: Evidence from a large sample study.

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.

Convergent creative thinking performance is associated with white matter structures: Evidence from a large sample study.

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 â€‹= â€‹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.

Increased grey matter volume of the right superior temporal gyrus in healthy children with autistic cognitive style: A VBM study.

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.

A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity.

Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women. Here we investigated the sex-specific effects of the CACNA1C variant rs1024582 on psychiatry-related traits, brain activity during tasks and rest, and brain volume in 1207 normal male and female subjects. After correcting for multiple comparisons, there were significant interaction effects between sex and the minor allele of this polymorphism on the hostile behavior subscale scores of the Coronary-Prone Type Scale mediated by higher scores in female carriers of the minor allele. Imaging analyses revealed significant interaction effects between sex and the minor allele on fractional amplitude of low-frequency fluctuations in the right dorsolateral prefrontal cortex and on brain activity during the 2-back task in areas of the right posterior cingulate cortex, right thalamus, and right hippocampus, which were all mediated by reduced activity in female carriers of the minor allele. Our results demonstrated that the rs1024582 risk variant of CACNA1C is associated with reduced activity in the frontolimbic regions at rest and during a working memory task as well as with greater hostility in females in the healthy population.

Impact of frequency of internet use on development of brain structures and verbal intelligence: Longitudinal analyses.

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.

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner.

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females.

Creative females have larger white matter structures: Evidence from a large sample study.

The importance of brain connectivity for creativity has been theoretically suggested and empirically demonstrated. Studies have shown sex differences in creativity measured by divergent thinking (CMDT) as well as sex differences in the structural correlates of CMDT. However, the relationships between regional white matter volume (rWMV) and CMDT and associated sex differences have never been directly investigated. In addition, structural studies have shown poor replicability and inaccuracy of multiple comparisons over the whole brain. To address these issues, we used the data from a large sample of healthy young adults (776 males and 560 females; mean age: 20.8 years, SD = 0.8). We investigated the relationship between CMDT and WMV using the newest version of voxel-based morphometry (VBM). We corrected for multiple comparisons over whole brain using the permutation-based method, which is known to be quite accurate and robust. Significant positive correlations between rWMV and CMDT scores were observed in widespread areas below the neocortex specifically in females. These associations with CMDT were not observed in analyses of fractional anisotropy using diffusion tensor imaging. Using rigorous methods, our findings further supported the importance of brain connectivity for creativity as well as its female-specific association. Hum Brain Mapp 38:414-430, 2017. © 2016 Wiley Periodicals, Inc.

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.

The impact of parent-child interaction on brain structures: cross-sectional and longitudinal analyses.

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.

Impact of reading habit on white matter structure: Cross-sectional and longitudinal analyses.

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.

The impact of television viewing on brain structures: cross-sectional and longitudinal analyses.

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.

Increased posterior hippocampal volumes in children with lower increase in body mass index: a 3-year longitudinal MRI study.

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.

Less Negative Implicit Attitudes Toward Autism Spectrum Disorder in University Students: A Comparison with Physical Disabilities.

People with autism spectrum disorder (ASD) experience stigmatization rooted in negative attitudes or prejudice toward them due to social awkwardness. However, little is known about implicit attitudes toward ASD, especially differences in attitudes compared to those of more visible conditions; physical disabilities. In this study, we implemented implicit association tests (IATs) to assess implicit attitudes. Sixty-three university students participated in IATs and answered questionnaires that measured explicit attitudes, social desirability, knowledge about-and familiarity with-disorders. The results demonstrated that implicit attitude toward ASD was significantly less negative than toward physical disabilities. Regarding the discrepancy, not socially awkward behavior but appearance of people with ASD can be evaluated as 'in-group' members and lead to less negative attitude compared with physical disabilities.

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.

Sex interaction of white matter microstructure and verbal IQ in corpus callosum in typically developing children and adolescents.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

A method to soothe and promote sleep in crying infants utilizing the transport response.

Approximately 20%-30% of infants cry excessively and exhibit sleep difficulties for no apparent reason, causing parental stress and even triggering impulsive child maltreatment in a small number of cases.1-8 While several sleep training methods or parental education programs may provide long-term improvement of infant cry and sleep problems, there is yet to be a conclusive recommendation for on-site behavioral interventions.9-13 Previously we have reported that brief carrying of infants transiently reduces infant cry via the transport response, a coordinated set of vagal activation and behavioral calming conserved in altricial mammals.14-18 In this study, we disentangled complex infant responses to maternal holding and transport by combining subsecond-scale, event-locked physiological analyses with dynamic mother-infant interactions. Infant cry was attenuated either by maternal carrying or by reciprocal motion provided by a moving cot, but not by maternal holding. Five-minute carrying promoted sleep for crying infants even in the daytime when these infants were usually awake, but not for non-crying infants. Maternal laydown of sleeping infants into a cot exerted bimodal effects, either interrupting or deepening the infants' sleep. During laydown, sleeping infants were alerted most consistently by the initiation of maternal detachment, then calmed after the completion of maternal detachment in a successful laydown. Finally, the sleep outcome after laydown was associated with the sleep duration before the laydown onset. These data propose a "5-min carrying, 5- to 8- min sitting" scheme for attending to infant cry and sleep difficulties, which should be further substantiated in future studies. VIDEO ABSTRACT.

Loneliness inside of the brain: evidence from a large dataset of resting-state fMRI in young adult.

Although loneliness itself is a natural emotion, prolonged loneliness is detrimental to human health. Despite its detrimental effect, few loneliness-related neuroimaging studies have been published and some have limitations on the sample size number. This study aims to find the difference in resting-state functional connectivity associated with loneliness within a big sample size via the seed-based approach. Functional connectivity analysis was performed on a large cohort of young adults (N = 1336) using the seed-based functional connectivity approach to address the concern from previous studies. The analysis yielded statistically significant positive correlations between loneliness and functional connectivities between the inferior frontal gyrus and supplementary motor area, precentral gyrus, and superior parietal lobule. Additionally, the analysis replicated a finding from a previous study, which is increased functional connectivities between the inferior frontal gyrus and supplementary motor area. In conclusion, greater loneliness is reflected by stronger functional connectivity of the visual attention brain area.