Combined and sequential exposure to prenatal second hand smoke and postnatal maternal distress is associated with cingulo-opercular global efficiency and attention problems in school-age children.

BACKGROUND: Prenatal exposure to secondhand (environmental) tobacco smoke (SHS) is associated with adverse neurodevelopmental outcomes, including altered functional activation of cognitive control brain circuitry and increased attention problems in children. Exposure to SHS is more common among Black youth who are also disproportionately exposed to socioeconomic disadvantage and concomitant maternal distress. We examine the combined effects of exposure to prenatal SHS and postnatal maternal distress on the global efficiency (GE) of the brain's cingulo-opercular (CO) and fronto-parietal control (FP) networks in childhood, as well as associated attention problems. METHODS: Thirty-two children of non-smoking mothers followed in a prospective longitudinal birth cohort at the Columbia Center for Children's Environmental Health (CCCEH) completed magnetic resonance imaging (MRI) at ages 7-9 years old. GE scores were extracted from general connectivity data collected while children completed the Simon Spatial Incompatibility functional magnetic resonance imaging (fMRI) task. Prenatal SHS was measured using maternal urinary cotinine from the third trimester; postnatal maternal distress was assessed at child age 5 using the Psychiatric Epidemiology Research Interview (PERI-D). The Child Behavior Checklist (CBCL) measured Attention and Attention Deficit Hyperactivity Disorder (ADHD) problems at ages 7-9. Linear regressions examined the interaction between prenatal SHS and postnatal maternal distress on the GE of the CO or FP networks, as well as associations between exposure-related network alterations and attention problems. All models controlled for age, sex, maternal education at prenatal visit, race/ethnicity, global brain correlation, and mean head motion. RESULTS: The prenatal SHS by postnatal maternal distress interaction term associated with the GE of the CO network (ß = 0.673, Bu = 0.042, t(22) = 2.427, p = .024, D = 1.42, 95% CI [0.006, 0.079], but not the FP network (ß = 0.138, Bu = 0.006, t(22) = 0.434, p = .668, 95% CI [-0.022, 0.033]). Higher GE of the CO network was associated with more attention problems (ß = 0.472, Bu = 43.076, t(23) = 2.780, p = .011, D = 1.74, n = 31, 95% CI [11.024, 75.128], n = 31) and ADHD risk (ß = 0.436, Bu = 21.961, t(29) = 2.567, p = .018, D = 1.81, 95% CI [4.219, 39.703], n = 30). CONCLUSIONS: These preliminary findings suggest that sequential prenatal SHS exposure and postnatal maternal distress could alter the efficiency of the CO network and increase risk for downstream attention problems and ADHD. These findings are consistent with prior studies showing that prenatal SHS exposure is associated with altered function of brain regions that support cognitive control and with ADHD problems. Our model also identifies postnatal maternal distress as a significant moderator of this association. These data highlight the combined neurotoxic effects of exposure to prenatal SHS and postnatal maternal distress. Critically, such exposures are disproportionately distributed among youth from minoritized groups, pointing to potential pathways to known mental health disparities.

Maternal education as an environmental factor related to reading in children with reading difficulties: A functional magnetic resonance imaging study.

The expanded simple view of reading (SVR) model suggests that word decoding, language comprehension and executive functions are necessary for reading comprehension. Children with reading difficulties (RDs) often have deficits in critical components of reading established in the expanded SVR model and alterations in brain function of reading-related regions. Maternal education could provide children with advantageous educational opportunities or resources that support reading acquisition. The primary goal of this study was to examine the contributions of maternal education to the behavioural and neurobiological correlates of the expanded SVR model. Seventy-two 8- to 12-year-old children with RDs and typical readers (TRs) completed reading, behavioural and an functional magnetic resonance imaging stories-listening task to determine the functional connectivity of the receptive language network to the whole brain in association with maternal education. Higher maternal education was associated with better vocabulary in children with RDs and positive functional connectivity between the receptive language network and regions related to visual processing in children with RDs versus TRs. These data suggest that maternal education supports the ability to comprehend oral language and engagement of neural networks that support imagination/visualization in children with RDs.

The Role of Environmental Chemicals in the Etiology of Learning Difficulties: A Novel Theoretical Framework.

Children from economically disadvantaged communities have a disproportionate risk of exposure to chemicals, social stress, and learning difficulties. Although animal models and epidemiologic studies link exposures and neurodevelopment, little focus has been paid to academic outcomes in environmental health studies. Similarly, in the educational literature, environmental chemical exposures are overlooked as potential etiologic factors in learning difficulties. We propose a theoretical framework for the etiology of learning difficulties that focuses on these understudied exogenous factors. We discuss findings from animal models and longitudinal, prospective birth cohort studies that support this theoretical framework. Studies reviewed point to the effects of prenatal exposure to polycyclic aromatic hydrocarbons on reading comprehension and math skills via effects on inhibitory control processes. Long term, this work will help close the achievement gap in the United States by identifying behavioral and neural pathways from prenatal exposures to learning difficulties in children from economically disadvantaged families.

COVID-19 Pandemic Experiences and Symptoms of Pandemic-Associated Traumatic Stress Among Mothers in the US.

Importance: The primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown. Objectives: To identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms. Design, Setting, and Participants: This multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022. Exposures: The primary exposures were pandemic-associated changes in mothers' health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators. Main Outcomes and Measures: The primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure. Results: The study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences-one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster. Conclusions and Relevance: In this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.

Effects of prenatal polycyclic aromatic hydrocarbons and childhood material hardship on reading achievement in school-age children: A preliminary study.

Background: Children from socioeconomically disadvantaged backgrounds are at elevated risk for reading problems. They are also likely to live in neighborhoods with high levels of air pollution and to experience material hardship. Despite these risk factors, the links between prenatal chemical exposures, socioeconomic adversities, and reading problems in youth from disadvantaged backgrounds remain understudied. Here we examine associations between prenatal exposure to polycyclic aromatic hydrocarbons (PAH), a common air pollutant, and reading skills, and determine if this relationship is exacerbated by material hardship among Black and/or Latinx children who have been followed as part of a longitudinal urban birth cohort. Methods: Mothers and their children, who were participants in a prospective birth cohort followed by the Columbia Center for Children's Environmental Health, were recruited for the current study. Personal prenatal PAH exposure was measured during the third-trimester of pregnancy using a personal air monitoring backpack. Mothers reported their level of material hardship when their child was age 5 and children completed measures of pseudoword and word reading [Woodcock Johnson III Tests of Achievement (WJ-III) Basic Reading Index] at age 7. We used multiple linear regression to examine the effects of the interaction between prenatal PAH and material hardship on Basic Reading Index, controlling for ethnicity/race, sex, birthweight, presence of a smoker in the home (prenatal), and maternal education (prenatal) (N = 53). Results: A prenatal PAH × material hardship interaction significantly associated with WJ-III Basic Reading Index scores at age 7 (ß = -0.347, t(44) = -2.197, p = 0.033). Exploratory analyses suggested that this effect was driven by untimed pseudoword decoding (WJ-III Word Attack: ß = -0.391, t(44) = -2.550, p = 0.014). Conclusion: Environmental chemical exposures can be particularly toxic during the prenatal period when the fetal brain undergoes rapid development, making it uniquely vulnerable to chemical perturbations. These data highlight the interactive effects of environmental neurotoxicants and unmet basic needs on children's acquisition of reading skill, specifically phonemic processing. Such findings identify potentially modifiable environmental risk factors implicated in reading problems in children from economically disadvantaged backgrounds.

Higher maternal education is related to negative functional connectivity between attention system networks and reading-related regions in children with reading difficulties compared to typical readers.

Ten to 15% of school-age children have reading difficulties (RD, or dyslexia), defined by deficits in phonological processing, fluency, and executive functions (EFs). Although RD is referred to as a genetic disorder, reading ability may also be affected by environmental factors such as inadequate exposure to literacy and a lack of parental involvement. These environmental components are a part of the socioeconomic status (SES) measure, which is defined by parental occupation, educational attainment, and household income and are positively correlated to reading ability. The goal of the current study was to relate maternal education, a construct of SES to executive functions (EFs) that relate to reading in children with RD compared to typical readers (TRs) using behavioral and neurobiological resting-state fMRI data. The results show that higher maternal education is negatively correlated to inhibitory control for TRs and not for children with RD. Higher maternal education was also associated with negative functional connectivity of the frontal-parietal network to the left central opercular cortex and left occipital gyrus for children with RD compared to TRs. These results suggest that higher maternal education has contrasting roles on the behavioral and neurobiological correlates of EFs for children with RD compared to TRs. We conclude that higher education levels for mothers may provide their children with a structured environment and educational resources that may assist their children with RD and TRs with cognitive development based on their reading profile.

Maternal depression is associated with decreased functional connectivity within semantics and phonology networks in preschool children.

INTRODUCTION: Maternal depression is characterized by a lack of emotional responsiveness and engagement with their child, which may lead to the child's decreased cognitive, and language outcomes all related to the child's future reading outcomes. The relations between maternal depression and functional connectivity in neural circuits supporting language in the child was explored. METHODS: Eleven 4-year-old girls completed language abilities assessment and resting-state functional magnetic resonance imaging scan. Their mothers completed the Beck's Depression Inventory (BDI) to examine maternal depression when the child was 12 months old and at the age of 4. Functional connections within the child's resting-state phonology, semantics, language networks were correlated with maternal BDI scores at the age of 4 years. RESULTS: Higher maternal depression was associated with the child's decreased within the semantic and phonological networks connectivity during rest. Higher maternal depression at 4 years moderated the relationship between early depression scores and functional connectivity within the phonological network. CONCLUSIONS: Maternal depression in the first year of life is related to functional connections of phonological processing and enhanced by current maternal depression levels. We conclude that after a mother gives birth, resources should be provided to minimize depressive symptoms and interventions should be applied to support their child's language development for future reading acquisition.

Longer Screen Vs. Reading Time is Related to Greater Functional Connections Between the Salience Network and Executive Functions Regions in Children with Reading Difficulties Vs. Typical Readers.

An adverse relationship between screen exposure time and brain functional/structural connectivity was reported in typically developing children, specifically related to neurobiological correlates of reading ability. As children with reading difficulties (RD) suffer from impairments in reading and executive functions (EF), we sought to determine the association between the ratio of screen time duration to reading time duration and functional connectivity of EF networks to the entire brain in children with RD compared to typical readers (TRs) using resting state data. Screen/reading time ratio was related to reduced reading and EF abilities. A larger screen/reading time ratio was correlated with increased functional connectivity between the salience network and frontal-EF regions in children with RD compared to TRs. We suggest that whereas greater screen/reading time ratio is related to excessive stimulation of the visual processing system in TRs, it may be related to decreased efficiency of the cognitive control system in RDs.

Maternal depression is associated with altered functional connectivity between neural circuits related to visual, auditory, and cognitive processing during stories listening in preschoolers.

BACKGROUND: Maternal depression can influence the early activity of a mother reading stories to a young child, as depressed mothers are less likely to read to their children. Here, maternal depression association to neurobiological circuitry of narrative comprehension, visualization, and executive functions during stories listening was examined in 21 4-year-old girls and their mothers. Maternal depression scores were collected from the mothers, and functional MRI during stories listening was collected from the children. RESULTS: Increased maternal depression was related to decreased functional connectivity between visualization and auditory regions and increased connectivity between the right visual cortex and dorsolateral prefrontal cortex in the children. CONCLUSIONS: This study highlights the need to monitor maternal depression and provide interventions to ensure positive linguistic outcomes in children.

Maternal reading fluency is associated with functional connectivity between the child's future reading network and regions related to executive functions and language processing in preschool-age children.

Reading is an acquired skill that relies on cognitive-control and language abilities. Home reading environment has been positively correlated with activation in parietal-temporal-occipital association cortex supporting mental imagery and narrative comprehension during a story-listening task in preschool-age children. However, the degree to which maternal reading ability influences early brain development, specifically neural circuits involved with language and reading, is not well understood. The current study explored the relationship between maternal reading ability and functional connectivity within the language network, between the language network and networks related to cognitive control and visual processing, as well as between the language network and the entire brain (network-to-voxel analysis) of preschool-age children during a resting state. Thirteen 4-year-old girls and their mothers participated in this study, involving cognitive testing and functional magnetic resonance imaging, including a resting-state scan. Maternal reading ability was negatively correlated with functional connectivity within the child's language network at rest, and also with areas involved in visual processing, cognitive-control, and semantics. These results suggest that children whose mothers exhibit decreased reading ability may demonstrate a greater engagement of the language network and neural circuits related to visual word recognition, cognitive-control, and semantic processing, which later in life support reading.

Systemic Elevation of Proinflammatory Interleukin 18 in HIV/HCV Coinfection versus HIV or HCV Monoinfection.

BACKGROUND: HIV/HCV coinfection and elevated interleukin (IL)-18 levels are both associated with enhanced progression of hepatic inflammation and increased risk of diabetes, kidney disease, and cardiovascular disease. IL-18 is a proinflammatory cytokine made upon activation of the inflammasome, an innate sensing system. We assessed whether increased IL-18 could explain the increased incidence and progression of inflammatory conditions seen with HIV/HCV coinfection. METHODS: Serum from 559 subjects with HIV monoinfection, HCV monoinfection, HIV/HCV coinfection, or people who inject drugs with neither infection was tested for IL-18 by ELISA and for 16 other analytes by electrochemiluminescence immunoassay. IL-18 levels were measured in 14 additional chronically HCV infected subjects who developed incident HIV infection to determine if IL-18 increases with coinfection. RESULTS: IL-18 was significantly elevated in coinfected individuals versus both monoinfections (p<0.0001) independent of age, sex, and race. IL-18 levels were significantly higher in HIV monoinfection than in HCV monoinfection. High IL-18 levels were correlated with detectable HIV viremia and inversely with CD4 count (p<0.0001), consistent with HIV activation of the inflammasome resulting in CD4 T cell depletion. Incident HIV infection of chronically HCV infected subjects resulted in increased IL-18 (p<0.001), while HIV suppression was associated with normal IL-18 levels. Four additional analytes (IP-10, IL-12/23p40, IFNy, IL-15) were found to be elevated in HIV/HCV coinfection when compared to both monoinfections. CONCLUSIONS: HIV/HCV coinfection results in significantly elevated serum IL-18. The elevated levels of this proinflammatory cytokine may explain the increased incidence and progression of inflammatory illnesses seen in coinfected individuals.

Regulation of flagellar, motility and chemotaxis genes in Rhizobium leguminosarum by the VisN/R-Rem cascade.

In this paper, we describe the regulatory roles of VisN, VisR and Rem in the expression of flagellar, motility and chemotaxis genes in Rhizobium leguminosarum biovar viciae strains VF39SM and 3841. Individual mutations in the genes encoding these proteins resulted in a loss of motility and an absence of flagella, indicating that these regulatory genes are essential for flagellar synthesis and function. Transcriptional experiments involving gusA-gene fusions in wild-type and mutant backgrounds were performed to identify the genes under VisN/R and Rem regulation. Results showed that the chemotaxis and motility genes of R. leguminosarum could be separated into two groups: one group under VisN/R-Rem regulation and another group that is independent of this regulation. VisN and VisR regulate the expression of rem, while Rem positively regulates the expression of flaA, flaB, flaC, flaD, motA, motB, che1 and mcpD. All of these genes except mcpD are located within the main motility and chemotaxis gene cluster of R. leguminosarum. Other chemotaxis and motility genes, which are found outside of the main motility gene cluster (che2 operon, flaH for VF39SM, and flaG) or are plasmid-borne (flaE and mcpC), are not part of the VisN/R-Rem regulatory cascade. In addition, all genes exhibited the same regulation pattern in 3841 and in VF39SM, except flaE and flaH. flaE is not regulated by VisN/R-Rem in 3841 but it is repressed by Rem in VF39SM. flaH is under VisN/R-Rem regulation in 3841, but not in VF39SM. A kinetics experiment demonstrated that a subset of the flagellar genes is continuously expressed in all growth phases, indicating the importance of continuous motility for R. leguminosarum under free-living conditions. On the other hand, motility is repressed under symbiotic conditions. Nodulation experiments showed that the transcriptional activators VisN and Rem are dramatically downregulated in the nodules, suggesting that the symbiotic downregulation of motility-related genes could be mediated by repressing the expression of VisN/R and Rem.