Examining Sex Differences in Autism Heritability.

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex. Objective: To estimate the sex-specific heritability of ASD. Design, Setting, and Participants: This was a population-based, retrospective analysis using national health registers of nontwin siblings and cousins from Sweden born between January 1, 1985, and December 31, 1998, with follow-up to 19 years of age. Data analysis occurred from August 2022 to November 2023. Main Outcomes and Measures: Models were fitted to estimate the relative variance in risk for ASD occurrence owing to sex-specific additive genetics, shared environmental effects, and a common residual term. The residual term conceptually captured other factors that promote individual behavioral variation (eg, maternal effects, de novo variants, rare genetic variants not additively inherited, or gene-environment interactions). Estimates were adjusted for differences in prevalence due to birth year and maternal and paternal age by sex. Results: The sample included 1 047 649 individuals in 456 832 families (538 283 males [51.38%]; 509 366 females [48.62%]). Within the entire sample, 12 226 (1.17%) received a diagnosis of ASD, comprising 8128 (1.51%) males and 4098 (0.80%) females. ASD heritability was estimated at 87.0% (95% CI, 81.4%-92.6%) for males and 75.7% (95% CI, 68.4%-83.1%) for females with a difference in heritability estimated at 11.3% (95% CI, 1.0%-21.6%). There was no support for shared environmental contributions. Conclusions and Relevance: These findings suggest that the degree of phenotypic variation attributable to genetic differences (heritability) differs between males and females, indicating that some of the underlying causes of the condition may differ between the 2 sexes. The skewed sex ratio in ASD may be partly explained by differences in genetic variance between the sexes.

Inflammatory Conditions During Pregnancy and Risk of Autism and Other Neurodevelopmental Disorders.

Background: Maternal inflammation can result from immune dysregulation and metabolic perturbations during pregnancy. Whether conditions associated with inflammation during pregnancy increase the likelihood of autism spectrum disorder (ASD) or other neurodevelopmental disorders (DDs) is not well understood. Methods: We conducted a case-control study among children born in California from 2011 to 2016 to investigate maternal immune-mediated and cardiometabolic conditions during pregnancy and risk of ASD (n = 311) and DDs (n = 1291) compared with children from the general population (n = 967). Data on maternal conditions and covariates were retrieved from electronic health records. Maternal genetic data were used to assess a causal relationship. Results: Using multivariable logistic regression, we found that mothers with asthma were more likely to deliver infants later diagnosed with ASD (odds ratio [OR] = 1.62, 95% CI: 1.15-2.29) or DDs (OR = 1.30, 95% CI: 1.02-1.64). Maternal obesity was also associated with child ASD (OR = 1.51, 95% CI: 1.07-2.13). Mothers with both asthma and extreme obesity had the greatest odds of delivering an infant later diagnosed with ASD (OR = 16.9, 95% CI: 5.13-55.71). These increased ASD odds were observed among female children only. Polygenic risk scores for obesity, asthma, and their combination showed no association with ASD risk. Mendelian randomization did not support a causal relationship between maternal conditions and ASD. Conclusions: Inflammatory conditions during pregnancy are associated with risk for neurodevelopmental disorders in children. These risks do not seem to be due to shared genetic risk; rather, inflammatory conditions may share nongenetic risk factors with neurodevelopmental disorders. Children whose mothers have both asthma and obesity during pregnancy may benefit from earlier screening and intervention.

Increased neural differentiation after a single session of aerobic exercise in older adults.

Aging is associated with decreased cognitive function. One theory posits that this decline is in part due to multiple neural systems becoming dedifferentiated in older adults. Exercise is known to improve cognition in older adults, even after only a single session. We hypothesized that one mechanism of improvement is a redifferentiation of neural systems. We used a within-participant, cross-over design involving 2 sessions: either 30 minutes of aerobic exercise or 30 minutes of seated rest (n = 32; ages 55-81 years). Both functional Magnetic Resonance Imaging (fMRI) and Stroop performance were acquired soon after exercise and rest. We quantified neural differentiation via general heterogeneity regression. There were 3 prominent findings following the exercise. First, participants were better at reducing Stroop interference. Second, while there was greater neural differentiation within the hippocampal formation and cerebellum, there was lower neural differentiation within frontal cortices. Third, this greater neural differentiation in the cerebellum and temporal lobe was more pronounced in the older ages. These data suggest that exercise can induce greater neural differentiation in healthy aging.

Moderate-to-vigorous intensity cycling exercise immediately after visual learning enhances delayed recognition memory performance.

A single bout of acute aerobic exercise has been shown to improve long-term memory, though it is unclear if exercise before learning or after learning is optimal for memory enhancement. Although some research has demonstrated that exercise before learning is ideal, investigations have consistently shown that acute arousal post-learning is a powerful memory enhancer. Therefore, the purpose of this investigation was to compare the effects of self-perceived hard cycling before or after learning on recognition memory for emotional and neutral images, and examine the relationship between central noradrenergic activity and memory performance. Seventy-two males and females (18-35 years of age) participated in this between-subjects study. Participants were randomly assigned to one of the following groups: exercise before learning, exercise after learning, and control. Participants in the exercise groups engaged in 20 min of cycling at a rating of perceived exertion (RPE) of 15 ("hard") on the Borg RPE scale before or after viewing a series of 90 pleasant, unpleasant, and neutral images (30 each). Participants in the control group engaged in no exercise before or after image viewing. At several time points throughout the experiment, saliva was collected to measure salivary alpha amylase (sAA), a marker of central noradrenergic activity. One-week later, recognition memory was assessed where participants viewed 180 images (90 new) and had to identify which images were previously viewed. Participants in the exercise after learning group had significantly higher recognition memory compared to the control group, but this was not seen with exercise before learning. sAA was not correlated with memory in any group, though it did increase during exercise. These results demonstrate that acute self-perceived hard cycling post-learning, but not pre-learning, improves recognition memory, though this was unrelated to the exercise-induced increase in central noradrenergic activity as measured in saliva.

Relationship between sex biases in gene expression and sex biases in autism and Alzheimer's disease.

Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-seq datasets using both within-region and pan-regional frameworks. We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-cell data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer's disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Finally, we provide region specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences.

Combinations of genes at the 16p11.2 and 22q11.2 CNVs contribute to neurobehavioral traits.

The 16p11.2 and 22q11.2 copy number variants (CNVs) are associated with neurobehavioral traits including autism spectrum disorder (ASD), schizophrenia, bipolar disorder, obesity, and intellectual disability. Identifying specific genes contributing to each disorder and dissecting the architecture of CNV-trait association has been difficult, inspiring hypotheses of more complex models, such as multiple genes acting together. Using multi-tissue data from the GTEx consortium, we generated pairwise expression imputation models for CNV genes and then applied these elastic net models to GWAS for: ASD, bipolar disorder, schizophrenia, BMI (obesity), and IQ (intellectual disability). We compared the variance in these five traits explained by gene pairs with the variance explained by single genes and by traditional interaction models. We also modeled polygene region-wide effects using summed predicted expression ranks across many genes to create a regionwide score. We found that in all CNV-trait pairs except for bipolar disorder at 22q11.2, pairwise effects explain more variance than single genes. Pairwise model superiority was specific to the CNV region for all 16p11.2 traits and ASD at 22q11.2. We identified novel individual genes over-represented in top pairs that did not show single-gene signal. We also found that BMI and IQ have significant regionwide association with both CNV regions. Overall, we observe that genetic architecture differs by trait and region, but 9/10 CNV-trait combinations demonstrate evidence for multigene contribution, and for most of these, the importance of combinatorial models appears unique to CNV regions. Our results suggest that mechanistic insights for CNV pathology may require combinational models.

A close-in giant planet escapes engulfment by its star.

When main-sequence stars expand into red giants, they are expected to engulf close-in planets1-5. Until now, the absence of planets with short orbital periods around post-expansion, core-helium-burning red giants6-8 has been interpreted as evidence that short-period planets around Sun-like stars do not survive the giant expansion phase of their host stars9. Here we present the discovery that the giant planet 8 Ursae Minoris b10 orbits a core-helium-burning red giant. At a distance of only 0.5 AU from its host star, the planet would have been engulfed by its host star, which is predicted by standard single-star evolution to have previously expanded to a radius of 0.7 AU. Given the brief lifetime of helium-burning giants, the nearly circular orbit of the planet is challenging to reconcile with scenarios in which the planet survives by having a distant orbit initially. Instead, the planet may have avoided engulfment through a stellar merger that either altered the evolution of the host star or produced 8 Ursae Minoris b as a second-generation planet11. This system shows that core-helium-burning red giants can harbour close planets and provides evidence for the role of non-canonical stellar evolution in the extended survival of late-stage exoplanetary systems.

A temperate Earth-sized planet with tidal heating transiting an M6 star.

Temperate Earth-sized exoplanets around late-M dwarfs offer a rare opportunity to explore under which conditions planets can develop hospitable climate conditions. The small stellar radius amplifies the atmospheric transit signature, making even compact secondary atmospheres dominated by N2 or CO2 amenable to characterization with existing instrumentation1. Yet, despite large planet search efforts2, detection of low-temperature Earth-sized planets around late-M dwarfs has remained rare and the TRAPPIST-1 system, a resonance chain of rocky planets with seemingly identical compositions, has not yet shown any evidence of volatiles in the system3. Here we report the discovery of a temperate Earth-sized planet orbiting the cool M6 dwarf LP 791-18. The newly discovered planet, LP 791-18d, has a radius of 1.03 ± 0.04 R⊕ and an equilibrium temperature of 300-400 K, with the permanent night side plausibly allowing for water condensation. LP 791-18d is part of a coplanar system4 and provides a so-far unique opportunity to investigate a temperate exo-Earth in a system with a sub-Neptune that retained its gas or volatile envelope. On the basis of observations of transit timing variations, we find a mass of 7.1 ± 0.7 M⊕ for the sub-Neptune LP 791-18c and a mass of [Formula: see text] for the exo-Earth LP 791-18d. The gravitational interaction with the sub-Neptune prevents the complete circularization of LP 791-18d's orbit, resulting in continued tidal heating of LP 791-18d's interior and probably strong volcanic activity at the surface5,6.

The Effects of Acute Resistance Exercise on Memory, Processing Speed, and Mood State After a Cognitive Challenge.

ABSTRACT: Venezia, AC, Barney, P, Spagnoli, D, Greco-Hiranaka, C, Piepmeier, AT, Smith, JC, and Weiss, LR. The effects of acute resistance exercise on memory, processing speed, and mood state after a cognitive challenge. J Strength Cond Res 37(9): 1738-1745, 2023-Acute moderate-to-vigorous-intensity aerobic exercise has been shown to improve learning and memory, but the effectiveness of acute high-intensity resistance exercise for improving memory is not fully understood. Like acute aerobic exercise, acute resistance exercise increases arousal and circulating catecholamines, mechanisms suggested to mediate the memory-enhancing effects of acute exercise. Furthermore, although acute exercise has been shown to benefit mood state, it is unknown if high-intensity resistance exercise positively influences mood state after a cognitive challenge. In this within-subjects design, subjects (18- to 25-year-old men) completed an approximately 40-minute session of resistance exercise or seated rest. Immediately after, the Automated Neuropsychological Assessment Metrics (ANAM) Code Substitution (CS)-Learning, CS-Immediate Recognition, and CS-Delayed Recognition tasks were completed, followed by the ANAM Mood Scale. There were no significant effects of exercise on recognition memory; however, CS-Learning (attention and processing speed) was better after resistance exercise ( p = 0.03). After the cognitive challenge, restlessness ( p < 0.001), vigor ( p = 0.03), and depression ( p = 0.047) scores were higher after resistance exercise compared with rest; however, after false discovery rate correction, only restlessness remained significantly different between sessions ( q = 0.002), whereas vigor ( q = 0.09) and depression ( q = 0.09) did not. These results suggest that an acute bout of resistance exercise improves attention and processing speed, although it does not improve recognition memory and has mixed effects on mood state in college-aged men.

Cardiorespiratory Fitness as a Moderator of Sleep-Related Associations with Hippocampal Volume and Cognition.

The objective of this study was to understand the associations of sleep and cardiorespiratory fitness with hippocampal volume and global cognition among older adults (n = 30, age = 65.8 years, female = 73.3%). Wrist actigraphy provided objective measures of nighttime sleep including sleep duration, average wake bout length (WBL; sleep disturbance), and wake-to-sleep transition probability (WTSP; sleep consolidation). Cardiorespiratory fitness was quantified via cycle exercise using a modified heart rate recovery approach. Magnetic resonance imaging was used to determine hippocampal volume and the Mini-Mental State Examination was used to assess global cognition. Fitness moderated associations of sleep with hippocampal volume and cognitive performance, whereby the association of WBL-an index of poor sleep-with hippocampal atrophy was stronger among less-fit individuals, and the association of sleep duration with cognitive performance was stronger among more-fit individuals. Across the fitness levels, a longer WBL was associated with lower cognitive performance, and a higher WTSP-an index of more consolidated sleep-was associated with greater hippocampal volume. Sleep and fitness were unrelated to the volume of an amygdala control region, suggesting a degree of neuroanatomical specificity. In conclusion, higher cardiorespiratory fitness may attenuate sleep disturbance-related hippocampal atrophy and magnify the cognitive benefits of good sleep. Prospective studies are needed to confirm these findings.

Design and construction of a quantum matter synthesizer.

The quantum matter synthesizer (QMS) is a new quantum simulation platform in which individual particles in a lattice can be resolved and re-arranged into arbitrary patterns. The ability to spatially manipulate ultracold atoms and control their tunneling and interactions at the single-particle level allows full control of a many-body quantum system. We present the design and characterization of the QMS, which integrates into a single ultra-stable apparatus a two-dimensional optical lattice, a moving optical tweezer array formed by a digital micromirror device, and site-resolved atomic imaging. We demonstrate excellent mechanical stability between the lattice and tweezer array with relative fluctuations below 10 nm, diffraction-limited imaging at a resolution of 655 nm, and high-speed real-time control of the tweezer array at a 2.52 kHz refresh rate, which will be adopted to realize fast rearrangement of atoms. The QMS also features new technologies and schemes, such as nanotextured anti-reflective windows and all-optical long-distance transport of atoms.

Can the "female protective effect" liability threshold model explain sex differences in autism spectrum disorder?

Male sex is a strong risk factor for autism spectrum disorder (ASD). The leading theory for a "female protective effect" (FPE) envisions males and females have "differing thresholds" under a "liability threshold model" (DT-LTM). Specifically, this model posits that females require either a greater number or larger magnitude of risk factors (i.e., greater liability) to manifest ASD, which is supported by the finding that a greater proportion of females with ASD have highly penetrant genetic mutations. Herein, we derive testable hypotheses from the DT-LTM for ASD, investigating heritability, familial recurrence, correlation between ASD penetrance and sex ratio, population traits, clinical features, the stability of the sex ratio across diagnostic changes, and highlight other key prerequisites. Our findings reveal that several key predictions of the DT-LTM are not supported by current data, requiring us to establish a different conceptual framework for evaluating alternate models that explain sex differences in ASD.

Sex-heterogeneous SNPs disproportionately influence gene expression and health.

Phenotypic differences across sexes are pervasive, but the genetic architecture of sex differences within and across phenotypes is mostly unknown. In this study, we aimed to improve detection power for sex-differentially contributing SNPs previously demonstrated to be enriched in disease association, and we investigate their functions in health, pathophysiology, and genetic function. We leveraged GIANT and UK Biobank summary statistics and defined a set of 2,320 independent SNPs having sexually dimorphic effects within and across biometric traits (MAF > 0.001, P < 5x10-8). Biometric trait sex-heterogeneous SNPs (sex-het SNPs) showed enrichment in association signals for 20 out of 33 diseases/traits at 5% alpha compared to sex-homogeneous matched SNPs (empP < 0.001), and were significantly overrepresented in muscle, skeletal and stem cell development processes, and in calcium channel and microtubule complexes (FDR < 0.05, empP < 0.05). Interestingly, we found that sex-het SNPs significantly map to predicted expression quantitative trait loci (Pr-eQTLs) across brain and other tissues, methylation quantitative trait loci (meQTLs) during development, and transcription start sites, compared to sex-homogeneous SNPs. Finally, we verified that the sex-het disease/trait enrichment was not explained by Pr-eQTL enrichment alone, as sex-het Pr-eQTLs were more enriched than matched sex-homogeneous Pr-eQTLs. We conclude that genetic polymorphisms with sexually dimorphic effects on biometric traits not only contribute to fundamental embryogenic processes, but later in life play an outsized role in disease risk. These sex-het SNPs disproportionately influence gene expression and have a greater influence on disorders of body and brain than other expression-regulatory variation. Together, our data emphasize the genetic underpinnings of sexual dimorphism and its role in human health.

Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes.

BACKGROUND: Deletions and duplications of the multigenic 16p11.2 and 22q11.2 copy number variant (CNV) regions are associated with brain-related disorders including schizophrenia, intellectual disability, obesity, bipolar disorder, and autism spectrum disorder (ASD). The contribution of individual CNV genes to each of these identified phenotypes is unknown, as well as the contribution of these CNV genes to other potentially subtler health implications for carriers. Hypothesizing that DNA copy number exerts most effects via impacts on RNA expression, we attempted a novel in silico fine-mapping approach in non-CNV carriers using both GWAS and biobank data. METHODS: We first asked whether gene expression level in any individual gene in the CNV region alters risk for a known CNV-associated behavioral phenotype(s). Using transcriptomic imputation, we performed association testing for CNV genes within large genotyped cohorts for schizophrenia, IQ, BMI, bipolar disorder, and ASD. Second, we used a biobank containing electronic health data to compare the medical phenome of CNV carriers to controls within 700,000 individuals in order to investigate the full spectrum of health effects of the CNVs. Third, we used genotypes for over 48,000 individuals within the biobank to perform phenome-wide association studies between imputed expressions of individual 16p11.2 and 22q11.2 genes and over 1500 health traits. RESULTS: Using large genotyped cohorts, we found individual genes within 16p11.2 associated with schizophrenia (TMEM219, INO80E, YPEL3), BMI (TMEM219, SPN, TAOK2, INO80E), and IQ (SPN), using conditional analysis to identify upregulation of INO80E as the driver of schizophrenia, and downregulation of SPN and INO80E as increasing BMI. We identified both novel and previously observed over-represented traits within the electronic health records of 16p11.2 and 22q11.2 CNV carriers. In the phenome-wide association study, we found seventeen significant gene-trait pairs, including psychosis (NPIPB11, SLX1B) and mood disorders (SCARF2), and overall enrichment of mental traits. CONCLUSIONS: Our results demonstrate how integration of genetic and clinical data aids in understanding CNV gene function and implicates pleiotropy and multigenicity in CNV biology.

Microstructural Plasticity in the Hippocampus of Healthy Older Adults after Acute Exercise.

INTRODUCTION: The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural magnetic resonance imaging. Critically, microstructural alterations within the hippocampus over short time intervals are associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. However, it is not yet known if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise. METHODS: We used a within-subject design to determine if a 30-min bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging measures in healthy older adults (n = 30) compared with a seated rest control condition. RESULTS: Significantly lower fractional anisotropy and higher mean diffusivity were found after exercise relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity. No significant differences in axial diffusivity were observed. CONCLUSIONS: These findings suggest that a single exercise session can lead to microstructural alterations in the hippocampus of healthy older adults. These differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations resulting from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus.

Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits.

BACKGROUND: The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits. METHODS: Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (rg < 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations. RESULTS: We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior). CONCLUSIONS: Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.

A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California.

BACKGROUND: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. METHODS: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. RESULTS: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. LIMITATIONS: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. CONCLUSIONS: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures.

Greater Semantic Memory Activation After Exercise Training Cessation in Older Endurance-Trained Athletes.

PURPOSE: To examine the effects of a 10-day exercise-training cessation on semantic memory functional activation in older distance runners. METHODS: Ten master runners (62.6 ± 7.0 years) with a long-term endurance-training history (29.0 ± 6.0 years) underwent a 10-day training cessation. Before and immediately after the training cessation, semantic memory activation was measured during the famous name recognition task, using functional magnetic resonance imaging. RESULTS: The 10-day training cessation resulted in greater semantic memory activation in three brain regions, including the left inferior frontal gyrus, parahippocampal gyrus, and inferior semilunar lobule. The 10-day training cessation did not significantly alter famous name recognition task performance. CONCLUSIONS: The findings demonstrate that even a relatively short period without exercise training alters the functional activation patterns of semantic memory-related neural networks. Increased semantic memory activation after training cessation may indicate reduced neural efficiency during successful memory retrieval.

Impact of exercise on older adults' mood is moderated by sleep and mediated by altered brain connectivity.

Older adults comprise the fastest growing global demographic and are at increased risk of poor mental health outcomes. Although aerobic exercise and sleep are critical to the preservation of emotional well-being, few studies have examined their combined mood-enhancing effects, or the potential neural mechanisms underlying these effects. Here, we used a randomized crossover design to test the impact of acute exercise on mood and the intrinsic functional connectivity (iFC) of the cingulo-opercular network in physically healthy older adults. Wrist actigraphy provided objective indices of sleep. Results revealed that 30 min of moderate-intensity aerobic exercise acutely enhanced positive affect (PA) and reduced iFC between the cingulo-opercular network and the hippocampus. Both effects were magnified among older adults with greater sleep disturbance. Exercise-induced changes in hippocampal iFC mediated relations between sleep disturbance and exercise-induced increases in PA. These findings provide evidence that aerobic exercise enhances mood, that it does so by altering connectivity between the anterior insula-a key hub in the cingulo-opercular network-and the hippocampus and that lower sleep quality is a stronger predictor of these effects among older adults. These observations underscore the benefits of moderate-intensity exercise-a safe and scalable behavioral intervention-and provide new clues about the neural circuitry underlying the interactive effects of sleep and exercise on mood.