Fine Motor Skills, a Surrogate of Motor Planning Ability, at Age 2 Predict Social Skills at Age 6.

OBJECTIVES: Motor planning is the cognitive process of planning necessary steps for achieving a purposeful movement and is specifically reflected through object manipulation. This study aimed to investigate whether fine motor skills, a surrogate of the motor planning ability of object manipulation, in early childhood are associated with later social skills, in a general-population birth cohort. METHODS: A total of 913 children, participating in the Hamamatsu Birth Cohort for Mothers and Children, were enrolled. Social skills were measured using the Vineland Adaptive Behavior Scales-II, Socialization domain, at age 6 years. Fine motor skills were measured using the Mullen Scales of Early Learning at 14, 24, and 32 months. The associations between fine motor skills at ages 14, 24, and 32 months and social skills at age 6 years were tested separately through multivariable linear regression after adjusting for covariates, including gross motor and language skills at the contemporaneous age, autistic symptoms at age 6 years, and demographic factors. RESULTS: Fine motor skills at 24 and 32 months were significantly associated with social skills at age 6 years (at 24 months: nonstandardized regression coefficient = 1.38 [95% CI, 0.50-2.26], p = 0.002; at 32 months: 1.47 [0.56-2.38], p = 0.001). CONCLUSION: Fine motor skills in early childhood predicted social skills at age 6 years, indicating an association between the complex motor planning ability of object manipulation and later social skills. Children who demonstrate fine motor delay at as early an age as 2 years should be closely monitored by child professionals.

The association between screen time and genetic risks for neurodevelopmental disorders in children.

Whether longer screen time in infancy increases risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and ADHD has long been debated, but no causal relationship between the two remains has been established. Using ongoing longitudinal cohort data, we found that in children 24 to 40 months of age, the genetic risk of ASD was associated with longer screen time and that of ADHD with an increase in screen time over time. These data suggest that prolonged screen time may not be a cause of the genetic risk for NDD, but an early sign of NDDs.

Interaction of genetic liability for attention deficit hyperactivity disorder (ADHD) and perinatal inflammation contributes to ADHD symptoms in children.

Objective: Genetic and environmental factors contribute to the development of Attention Deficit/Hyperactivity Disorder (ADHD). Perinatal inflammation is one of the promising environmental risk factors for ADHD, but the relationship between the genetic risk for ADHD and perinatal inflammation requires further examination. Methods: A possible gene-environmental interaction between perinatal inflammation and ADHD polygenic risk score (ADHD-PRS) on ADHD symptoms was investigated in children aged 8-9 from the Hamamatsu Birth Cohort for Mothers and Children (N = 531). Perinatal inflammation was evaluated by the level of concentration of three cytokines assayed in umbilical cord blood. The genetic risk for ADHD was assessed by calculating ADHD-PRS for each individual using a previously collected genome-wide association study of ADHD. Results: Perinatal inflammation (ß [SE], 0.263 [0.017]; P < 0.001), ADHD-PRS (ß [SE], 0.116[0.042]; P = 0.006), and an interaction between the two (ß [SE], 0.031[0.011]; P = 0.010) were associated with ADHD symptoms. The association between perinatal inflammation and ADHD symptoms measured by ADHD-PRS was evident only in the two higher genetic risk groups (ß [SE], 0.623[0.122]; P < 0.001 for the medium-high risk group; ß [SE], 0.664[0.152]; P < 0.001 for the high-risk group). Conclusion: Inflammation in the perinatal period both directly elevated ADHD symptoms and magnified the impact of genetic vulnerability on ADHD risk particularly among children aged 8-9 with genetically higher risk for ADHD.

Determinants and Projections of Minimum Acceptable Diet among Children Aged 6-23 Months: A National and Subnational Inequality Assessment in Bangladesh.

Subnational evidence on the level of inequality in receiving complementary feeding practice among Bangladeshi children is lacking. This study estimated inequality in the minimum acceptable diet (MAD) among Bangladeshi children aged 6-23 months, and identified risk factors for and developed projections of the MAD up to 2030. Data from the Bangladesh Demographic and Health Survey 2017-2018 were used in this cross-sectional study. Regression-based slope (SII) and relative index of inequality (RII) were used to quantify the level of absolute and relative inequality, respectively. A Bayesian logistic regression model was used to identify the potential determinants of a MAD and project prevalence up to 2030. About 38% of children aged 6-23 months received a MAD. The national prevalence of a MAD was 26.0 percentage points higher among children from the richest compared to the poorest households, and 32.1 percentage points higher among children of higher-educated over illiterate mothers. Socioeconomic inequality was found to be the highest in the Chattogram division (SII: 43.9), while education-based inequality was highest in the Sylhet division (SII: 47.7). Maternal employment and the number of ANC visits were also identified as significant determinants of a MAD, and the prevalence of a MAD was projected to increase from 42.5% in 2020 to 67.9% in 2030. Approximately two out of five children received a MAD in Bangladesh and significant socioeconomic and education-based inequalities in the MAD were observed. Subnational variation in socioeconomic and education-based inequalities in the MAD requires further public health attention, and poverty reduction programs need to be strengthened.

Outdoor Play as a Mitigating Factor in the Association Between Screen Time for Young Children and Neurodevelopmental Outcomes.

Importance: Whether the association between higher screen time in infancy and later suboptimal neurodevelopment can be mitigated by frequency of outdoor play is unknown. Objective: To investigate whether higher screen time at age 2 years is associated with neurodevelopmental outcomes at age 4 years and whether this association is mediated by frequency of outdoor play at age 2 years 8 months. Design, Setting, and Participants: Participants were a subsample of the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study, N = 1258). Children were born between December 2007 and March 2012 and followed up from 1 year 6 months to 4 years. The analysis was conducted from April 2021 to June 2022. Exposures: Screen time longer than 1 hour a day at age 2 years was coded as higher screen time. Main Outcomes and Measures: Standardized scores for communication, daily living skills, and socialization domains of the Vineland Adaptive Behavior Scale, second edition, at age 4 years were used (mean [SD], 100 [15]). The mediating factor was frequency of outdoor play at age 2 years 8 months, with 6 or 7 days per week coded as frequent outdoor play. Results: Of 885 participants, 445 children (50%) were female; mean (SD) screen time per day was 2.6 (2.0) hours. Causal mediation analyses revealed that higher screen time at age 2 years was associated with lower scores in communication at age 4 years (nonstandardized coefficient b = -2.32; 95% CI, -4.03 to -0.60), but the association was not mediated by frequency of outdoor play. Higher screen time was also associated with lower scores in daily living skills (b = -1.76; 95% CI, -3.21 to -0.31); 18% of this association was mediated by frequency of outdoor play. Frequency of outdoor play was associated with socialization (b = 2.73; 95% CI, 1.06 to 4.39), whereas higher screen time was not (b = -1.34; 95% CI, -3.05 to 0.36). Conclusions and Relevance: Higher screen time at age 2 years was directly associated with poorer communication at age 4 years. It was also associated with daily living skills, but frequency of outdoor play at age 2 years 8 months alleviated it, suggesting outdoor play mitigated the association between higher screen time and suboptimal neurodevelopment. Future research should specify the nature of the associations and intervention measures, enabling targeted interventions that reduce the potential risk in screen time.

Sex differences in neurodevelopmental trajectories in children with different levels of autistic traits.

AIM: Little is known about early manifestations of autism spectrum disorders (ASD) in females, including those who may be overlooked by the current diagnostic criteria. We longitudinally explored sex differences in the trajectories of cognitive and motor functions and adaptive behaviors in children with different levels of autistic traits. METHODS: The participants were 824 children from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study), Japan, who were classified into three autistic trait groups-low, moderate, and high-based on the Social Responsiveness Scale-Second Edition. Cognitive and motor functions were measured at seven time-points from 0.5 to 3.5 years of age using the Mullen Scales of Early Learning. Adaptive behaviors were measured at five time-points from 2.7 to 9 years of age using the Vineland Adaptive Behavior Scales-Second Edition. Trajectories were depicted using latent growth curve modeling. RESULTS: Sex-specific trajectories were observed in the high-autistic-trait group, with only males showing a temporary decline in expressive language around the age of 2 years and a slight improvement thereafter. They also showed a slight improvement around 3 years in the adaptive behavior communication domain but a gradual downward trend later. Females in the high-autistic-trait group showed no distinct manifestation before the age of 3 years but showed a downward trend after 3.5 years in the adaptive behavior communication domain. CONCLUSION: Females and males with higher autistic traits than their same-sex peers, independent of clinical diagnosis, may have different phenotypes in certain neurodevelopmental domains during infancy and early childhood.

Lower Availability of Mitochondrial Complex I in Anterior Cingulate Cortex in Autism: A Positron Emission Tomography Study.

OBJECTIVE: Mitochondrial dysfunction has been implicated in the pathophysiology of autism spectrum disorder (ASD) in previous studies of postmortem brain or peripheral samples. The authors investigated whether and where mitochondrial dysfunction occurs in the living brains of individuals with ASD and to identify the clinical correlates of detected mitochondrial dysfunction. METHODS: This case-control study used positron emission tomography (PET) with 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF), a radioligand that binds to the mitochondrial electron transport chain complex I, to examine the topographical distribution of mitochondrial dysfunction in living brains of individuals with ASD. Twenty-three adult males with high-functioning ASD, with no psychiatric comorbidities and free of psychotropic medication, and 24 typically developed males with no psychiatric diagnoses, matched with the ASD group on age, parental socioeconomic background, and IQ, underwent [18F]BCPP-EF PET measurements. Individuals with mitochondrial disease were excluded by clinical evaluation and blood tests for abnormalities in lactate and pyruvate levels. RESULTS: Among the brain regions in which mitochondrial dysfunction has been reported in postmortem studies of autistic brains, participants with ASD had significantly decreased [18F]BCPP-EF availability specifically in the anterior cingulate cortex compared with typically developed participants. The regional specificity was revealed by a significant interaction between diagnosis and brain regions. Moreover, the lower [18F]BCPP-EF availability in the anterior cingulate cortex was significantly correlated with the more severe ASD core symptom of social communication deficits. CONCLUSIONS: This study provides direct evidence to link in vivo brain mitochondrial dysfunction with ASD pathophysiology and its communicational deficits. The findings support the possibility that mitochondrial electron transport chain complex I is a novel therapeutic target for ASD core symptoms.

Neural mechanisms underlying rule selection based on response evaluation: a near-infrared spectroscopy study.

The ability of humans to use rules for organizing action demands a high level of executive control. Situational complexity mediates rule selection, from the adoption of a given rule to the selection of complex rules to achieve an appropriate response. Several rules have been proposed to be superordinate to human behavior in a cognitive hierarchy and mediated by different brain regions. In the present study, using a novel rule-selection task based on pre-response evaluations that require several cognitive operations, we examined whether the task is mediated by a specific region of the prefrontal cortex using near-infrared spectroscopy. We showed that the selection of rules, including prior evaluation of a stimulus, activates broader areas of the prefrontal and premotor regions than response selection based on a given rule. The results are discussed in terms of hierarchical cognitive models, the functional specialization of multiple-cognitive operations in the prefrontal cortex, and their contribution to a novel cognitive task.

Trajectories of Adaptive Behaviors During Childhood in Females and Males in the General Population.

Little is known about the trajectory patterns and sex differences in adaptive behaviors in the general population. We examined the trajectory classes of adaptive behaviors using a representative sample and examined whether the class structure and trajectory patterns differed between females and males. We further explored sex differences in neurodevelopmental traits in each latent class. Participants (n = 994) were children in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study)-a prospective birth cohort study. Adaptive behaviors in each domain of communication, daily living skills, and socialization were evaluated at five time points when participants were 2.7, 3.5, 4.5, 6, and 9 years old using the Vineland Adaptive Behavior Scales-Second Edition. Parallel process multigroup latent class growth analysis extracted sex-specific trajectory classes. Neurodevelopmental traits of children at age 9, autistic traits, attention deficit hyperactivity disorder (ADHD) traits, and cognitive ability were examined for females and males in each identified class. A 4-class model demonstrated the best fit. Moreover, a 4-class model that allowed for differences in class probabilities and means of growth parameters between females and males provided a better fit than a model assuming no sex differences. In the communication domain, females scored higher than their male counterparts in all four classes. In the daily living skills and socialization domains, the two higher adaptive classes (Class 1: females, 18.6%; males, 17.8%; Class 2: females, 48.8%; males, 49.8%) had similar trajectories for males and females, whereas in the two lower adaptive behavior classes (Class 3: females, 27.5%; males, 29.4%; Class 4: females, 5.1%; males, 3.0%), females had higher adaptive scores than their male counterparts. In Class 4, females were more likely to have autistic and ADHD traits exceeding the cutoffs, while males were more likely to have below-average IQ. Different trajectories in females and males suggest that adaptive skills may require adjustment based on the sex of the child, when standardizing scores, in order to achieve better early detection of skill impairment.

Identification of neurodevelopmental transition patterns from infancy to early childhood and risk factors predicting descending transition.

It is unclear whether neurodevelopmental progress from infancy to early childhood remains stable. Moreover, little is known about the risk factors, if any, affecting neurodevelopmental descending transition patterns and the relationship between these patterns and later childhood adaptive behaviours. We used data of 875 children from the Hamamatsu Birth Cohort Study in Japan. Children's neurodevelopment at 18 and 32 months and adaptive behaviours at 40 months were evaluated. Perinatal factors and infant overweight status at 18 months were investigated to identify descending-transition-associated risk factors. In the latent transition analysis, ultimately, three classes were identified for each time-point, resulting in nine transition patterns; among them, 10.4% of children showed descending class shifts (normal to delayed class). Such decelerated growth was predicted by maternal pre-pregnancy overweight status (odds ratio [OR] 2.49; 95% confidence interval [CI] 1.23, 5.02), low maternal educational history (OR 1.20; 95% CI 1.04, 1.36), and infant overweight status at 18 months (OR 5.89; 95% CI 1.26, 27.45). Children with descending transition showed poor functioning in adaptive behaviours at the age of 40 months. To prevent subsequent poor adaptive functioning, it may be necessary to consider that a certain percentage of children show decelerated growth.

Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study.

The social motivation hypothesis of autism proposes that social communication symptoms in autism-spectrum disorder (ASD) stem from atypical social attention and reward networks, where dopamine acts as a crucial mediator. However, despite evidence indicating that individuals with ASD show atypical activation in extrastriatal regions while processing reward and social stimuli, no previous studies have measured extrastriatal dopamine D2/3 receptor (D2/3R) availability in ASD. Here, we investigated extrastriatal D2/3R availability in individuals with ASD and its association with ASD social communication symptoms using positron emission tomography (PET). Moreover, we employed a whole-brain multivariate pattern analysis of resting-state functional magnetic resonance imaging (fMRI) to identify regions where functional connectivity atypically correlates with D2/3R availability depending on ASD diagnosis. Twenty-two psychotropic-free males with ASD and 24 age- and intelligence quotient-matched typically developing males underwent [11C]FLB457 PET, fMRI, and clinical symptom assessment. Participants with ASD showed lower D2/3R availability throughout the D2/3R-rich extrastriatal regions of the dopaminergic pathways. Among these, the posterior region of the thalamus, which primarily comprises the pulvinar, displayed the largest effect size for the lower D2/3R availability, which correlated with a higher score on the Social Affect domain of the Autism Diagnostic Observation Schedule-2 in participants with ASD. Moreover, lower D2/3R availability was correlated with lower functional connectivity of the thalamus-superior temporal sulcus and cerebellum-medial occipital cortex, specifically in individuals with ASD. The current findings provide novel molecular evidence for the social motivation theory of autism and offer a novel therapeutic target.

Long-term effect of persistent postpartum depression on children's psychological problems in childhood.

BACKGROUND: Maternal postpartum depression (PPD) is a well-established risk factor for psychological problems in children; however, little is known about the sustained impact of persistent PPD patterns and severity on these problems in children. METHODS: Data were obtained from mothers (N = 714) and children (N = 768) from the Hamamatsu Birth Cohort for Mothers and Children. Maternal depression was measured using the Edinburgh Postpartum Depression Scale at 2, 4, 10 weeks and 10 months postpartum. Children's internalizing and externalizing problems were assessed using the Strengths and Difficulties Questionnaire at 6 years and 8-9 years old. Mothers were divided into 4 groups based on the trajectory of their PPD persistence: "No PPD," "Transient PPD," "Worsening PPD" and "Persistent PPD." Linear regression analysis was used to examine the association of PPD persistence and severity with children's internalizing and externalizing problems. RESULTS: "Persistent PPD" was significantly associated with children's internalizing problems at 6 years old (Coefficient [95%CI] = 2.74 [1.30-4.19], P < .001), but no association was found at 8-9 years old. No associations were found between PPD severity and children's internalizing and externalizing problems in either age category. LIMITATIONS: "Persistent PPD" and "Worsening PPD" groups had a relatively small sample size. The mothers' depression statuses were not ascertained simultaneously with the children's behavioral assessments. There was no information regarding the mothers' treatment for PPD. CONCLUSION: PPD persistence negatively affected children's internalizing problems but was not long-lasting. Future studies are needed to identify protective factors against PPD persistence in children's psychological problems.

Early temperament as a predictor of language skills at 40 months.

BACKGROUND: Mastering language involves the development of expressive and receptive skills among children. While it has been speculated that early temperament plays a role in the acquisition of language, the actual mechanism has not yet been explored. We investigated whether temperament at 18 months predicted expressive or receptive language skills at 40 months. METHODS: A representative sample of 901 children and their mothers who were enrolled and followed-up longitudinally in the Hamamatsu Birth Cohort for Mothers and Children study was included in the analysis. Child temperament was measured at 18 months using the Japanese version of the Early Childhood Behavior Questionnaire. Expressive and receptive language skills were measured at 40 months using the Mullen Scales of Early Learning. RESULTS: The multiple regression analysis, adjusting for potential confounders, suggested that higher motor activation (fidgeting) at 18 months was associated with lower expressive and receptive language skills at 40 months. Higher perceptual sensitivity was associated with higher expressive and receptive language skills at 40 months. CONCLUSIONS: Specific temperament at 18 months of age predicted the development of the child's expressive and receptive language skills at 40 months.

Umbilical cord serum concentrations of perfluorooctane sulfonate, perfluorooctanoic acid, and the body mass index changes from birth to 5 1/2 years of age.

Prenatal exposure to perfluoroalkyl substances (PFAS) has been reported to affect body weight from birth to childhood, but the results remain inconclusive. We investigated whether umbilical cord blood concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are associated with children's risk trajectory for obesity. 600 children were randomly selected from the Hamamatsu Birth Cohort for Mothers and Children (HBC study) and their umbilical cord serum PFAS concentrations were quantified. Participants underwent BMI measurements at ages 1, 4, 10, 18, 24, 32, 40, 50, and 66 months. Growth curve modeling with random intercept was performed with standardized BMI as outcome variable. PFOS was negatively associated with standardized BMI (ß = - 0.34; p = 0.01), with a marginally significant interaction with the child's age (ß = 0.0038; p = 0.08). PFOA was negatively associated with standardized BMI (ß = - 0.26, 95% CI - 0.51, 0; p = 0.05), with a significant interaction with the child's age (ß = 0.005; p = 0.01). Stratified analysis by sex revealed that these effects were significant only among girls. Prenatal exposure to PFAS initially was associated with lower standardized BMI during infancy, but this effect dissipated over time and reversed in direction during later childhood. The effects of prenatal PFAS on higher standardized BMI is stronger in girls.

Association Between Genetic Risks for Obesity and Working Memory in Children.

Introduction: Obesity is highly heritable, and recent evidence demonstrates that obesity is associated with cognitive deficits, specifically working memory. However, the relationship between genetic risks for obesity and working memory is not clear. In addition, whether the effect of these genetic risks on working memory in children is mediated by increased body mass index (BMI) has not been elucidated. Methods: In order to test whether the polygenic risk score (PRS) for obesity in adulthood (adulthood-BMI-PRS) is associated with working memory at 8 years of age, and whether the effect is mediated by childhood BMI, in children from the general population, participants in the Hamamatsu Birth Cohort for Mothers and Children (HBC) study in Hamamatsu, Japan, underwent testing for association of adulthood-BMI-PRS with working memory. HBC data collection began in December 2007 and is ongoing. Adulthood-BMI-PRS values were generated using summary data from the recent genome-wide association study (GWAS) undertaken in Japan, and the significance of thresholds was calculated for each outcome. Outcomes measured included the working memory index (WMI) of Weschler Intelligence Scale-4 (WISC-IV) scores and the BMI at 8 years of age. Gene-set enrichment analysis was conducted to clarify the molecular basis common to adulthood-BMI and childhood-WMI. Mediation analysis was performed to assess whether childhood-BMI of children mediated the association between adulthood-BMI-PRS and working memory. Results: A total of 734 participants (377 males, 357 females) were analyzed. Adulthood-BMI-PRS was associated with lower childhood-WMI (ß[SE], -1.807 [0.668]; p = 0.010, corrected) of WISC-IV. Gene-set enrichment analyses found that regulation of neurotrophin Trk receptor signaling (ß[SE], -2.020 [6.39]; p = 0.002, corrected), negative regulation of GTPase activity (ß[SE], 2.001 [0.630]; p = 0.002, corrected), and regulation of gene expression epigenetic (ß[SE], -2.119 [0.664]; p = 0.002, corrected) were enriched in BMI in adulthood and WMI in childhood. Mediation analysis showed that there is no mediation effect of childhood-BMI between the adulthood-BMI-PRS and working memory deficits in children. Conclusion: Adulthood-BMI-PRS was associated with working memory among children in the general population. These genetic risks were not mediated by the childhood-BMI itself and were directly associated with working memory deficits.

Elevated risk of attention deficit hyperactivity disorder (ADHD) in Japanese children with higher genetic susceptibility to ADHD with a birth weight under 2000 g.

BACKGROUND: Both genetic and pre- and perinatal factors, including birth weight, have been implicated in the onset of attention deficit hyperactivity disorder (ADHD) traits among children. This study aimed to elucidate to what extent the genetic risk of ADHD moderates the association between birth weight and ADHD traits among Japanese children. METHODS: We conducted a longitudinal birth cohort study (Hamamatsu Birth Cohort for Mother and Children Study) to investigate the association of genetic risk for ADHD and low birth weight with ADHD traits among Japanese children. Out of 1258 children, we included 796 who completed follow-ups at 8 to 9 years of age. Birth weight was categorized as <2000 g, 2000-2499 g, and ≥2500 g. Polygenic risk score for ADHD was generated using the summary data of a large-scale genome-wide association study. The Rating Scale IV (ADHD-RS) assessed ADHD traits (inattention and hyperactivity/impulsivity) based on parental reports. Following previous studies, sex, birth order of the child, gestational age at birth, mother's age at delivery, educational attainment, pre-pregnancy body mass index, pre-pregnancy or during pregnancy smoking status, alcohol consumption during pregnancy, father's age, education, and annual family income were considered as covariates. Multivariable negative binomial regression was applied to evaluate the association between birth weight and ADHD traits, while adjusting for potential covariates. The interaction term between birth weight categories and binary polygenic risk was added to the model. RESULTS: Birth weight of 2000-2499 g was not associated with ADHD traits. Birth weight under 2000 g was significantly associated with both inattention and hyperactivity. When accounting for higher and lower genetic risk for ADHD, only those with higher genetic risk and birth weight < 2000 g were associated with inattention (rate ratio [RR] 1.56, 95% CI 1.07-2.27) and hyperactivity (RR 1.87, 95% CI 1.14-3.06). CONCLUSIONS: Birth weight under 2000 g, together with the genetic risk of ADHD, contributes to higher levels of ADHD traits among Japanese children aged 8 to 9 years. The suggested association between low birth weight and ADHD is confined to children with a genetic susceptibility to ADHD, indicating the relevance of genetic-environmental interactions in the etiology.

How Memory Switches Brain Responses of Patients with Post-traumatic Stress Disorder.

To characterize the brain responses to traumatic memories in post-traumatic stress disorder (PTSD), we conducted task-employed functional magnetic resonance imaging and, in the process, devised a simple but innovative approach-correlation computation between task conditions. A script-driven imagery task was used to compare the responses with a script of the patients' own traumatic memories and with that of tooth brushing as a daily activity and to evaluate how eye movement desensitization and reprocessing (EMDR), an established therapy for PTSD, resolved the alterations in patients. Nine patients with PTSD (seven females, aged 27-50 years) and nine age- and gender-matched healthy controls participated in this study. Six patients underwent the second scan under the same paradigm after EMDR. We discovered intense negative correlations between daily and traumatic memory conditions in broad areas, including the hippocampus; patients who had an intense suppression of activation during daily recognition showed an intense activation while remembering a traumatic memory, whereas patients who had a hyperarousal in daily recognition showed an intense suppression while remembering a traumatic memory as a form of "shut-down." Moreover, the magnitude of the discrepancy was reduced in patients who remitted after EMDR, which might predict an improved prognosis of PTSD.

Associations Among Maternal Metabolic Conditions, Cord Serum Leptin Levels, and Autistic Symptoms in Children.

INTRODUCTION: Accumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet. METHODS: This study investigated the associations between mothers' metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8-9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). RESULTS: Umbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081-1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206-2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000-1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant. DISCUSSION: The present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.

When a sentence loses semantics: Selective involvement of a left anterior temporal subregion in semantic processing.

Although the left anterior temporal lobe (ATL) has been associated with semantic processing, the role of this region in syntactic structure building of sentences remains a subject of debate. Functional neuroimaging studies contrasting well-formed sentences with word lists lacking syntactic structure have produced mixed results. The current functional magnetic resonance imaging study examined whether the left ATL is selectively involved in semantic processing or also plays a role in syntactic structure building by manipulating syntactic complexity and meaningfulness in a novel way. To deprive semantic/pragmatic information from a sentence, we replaced all content words with pronounceable meaningless placeholders. We conducted an experiment with a 2 × 2 factorial design with factors of SEMANTICS (natural sentences [NAT]; sentences with placeholders [SPH]) and SYNTAX (the basic Japanese Subject-Object-Verb [SOV] word order; a changed Object-Subject-Verb [OSV] word order). A main effect of SEMANTICS (NAT > SPH) was found in the left ATL, as well as in the ventral occipitotemporal regions. The opposite contrast (SPH > NAT) revealed activation in the dorsal regions encompassing Brodmann area 44, the premotor area, and the parietal cortex in the left hemisphere. We found no main effect of SYNTAX (OSV > SOV) in a subregion of the left ATL that was more responsive to natural sentences than meaningless sentences. These results indicate selective involvement of a subregion of the left ATL in semantic/pragmatic processing.