Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty.

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how growing up in a low resource setting might exacerbate the link between inhibitory control and health outcomes. In this context we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyrus, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

Brain morphometry and diminished physical growth in Bangladeshi children growing up in extreme poverty: A longitudinal study.

Diminished physical growth is a common marker of malnutrition and it affects approximately 200 million children worldwide. Despite its importance and prevalence, it is not clear whether diminished growth relates to brain development and general cognitive ability. Further, diminished growth is more common in areas of extreme poverty, raising the possibility that it may mediate previously shown links between socioeconomic status (SES) and brain structure. To address these gaps, 79 children growing up in an extremely poor, urban area of Bangladesh underwent MRI at age six years. Structural brain images were submitted to Mindboggle software, a Docker-compliant and high-reproducibility tool for tissue segmentation and regional estimations of volume, surface area, cortical thickness, sulcal depth, and mean curvature. Diminished growth predicted brain morphometry and mediated the link between SES and brain morphometry most consistently for subcortical and white matter subcortical volumes. Meanwhile, brain volume in left pallidum and right ventral diencephalon mediated the relationship between diminished growth and full-scale IQ. These findings offer malnutrition as one possible pathway through which SES affects brain development and general cognitive ability in areas of extreme poverty.

Relating anthropometric indicators to brain structure in 2-month-old Bangladeshi infants growing up in poverty: A pilot study.

Anthropometric indicators, including stunting, underweight, and wasting, have previously been associated with poor neurocognitive outcomes. This link may exist because malnutrition and infection, which are known to affect height and weight, also impact brain structure according to animal models. However, a relationship between anthropometric indicators and brain structural measures has not been tested yet, perhaps because stunting, underweight, and wasting are uncommon in higher-resource settings. Further, with diminished anthropometric growth prevalent in low-resource settings, where biological and psychosocial hazards are most severe, one might expect additional links between measures of poverty, anthropometry, and brain structure. To begin to examine these relationships, we conducted an MRI study in 2-3-month-old infants growing up in the extremely impoverished urban setting of Dhaka, Bangladesh. The sample size was relatively small because the challenges of investigating infant brain structure in a low-resource setting needed to be realized and resolved before introducing a larger cohort. Initially, fifty-four infants underwent T1 sequences using 3T MRI, and resulting structural images were segmented into gray and white matter maps, which were carefully evaluated for accurate tissue labeling by a pediatric neuroradiologist. Gray and white matter volumes from 29 infants (79 â€‹± â€‹10 days-of-age; F/M â€‹= â€‹12/17), whose segmentations were of relatively high quality, were submitted to semi-partial correlation analyses with stunting, underweight, and wasting, which were measured using height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) scores. Positive semi-partial correlations (after adjusting for chronological age and sex and correcting for multiple comparisons) were observed between white matter volume and HAZ and WAZ; however, WHZ was not correlated with any measure of brain volume. No associations were observed between income-to-needs or maternal education and brain volumetric measures, suggesting that measures of poverty were not associated with total brain tissue volume in this sample. Overall, these results provide the first link between diminished anthropometric growth and white matter volume in infancy. Challenges of conducting a developmental neuroimaging study in a low-resource country are also described.

Increased Fecal Lactobacillus Is Associated With a Positive Glucose Hydrogen Breath Test in Bangladeshi Children.

BACKGROUND: Glucose hydrogen breath testing is a noninvasive test for small intestine bacterial overgrowth (SIBO). A positive glucose hydrogen breath test is common in children from low-income countries and has been found to be associated with malnutrition as measured by stunted growth. The microbiome associated with positive breath testing is relatively unstudied. METHODS: We performed 16 S V4 rDNA microbiome analysis on the stool of 90 Bangladeshi children aged 2 years from an impoverished neighborhood who were tested at the same time for SIBO by glucose hydrogen breath testing. Data were analyzed by linear discriminant analysis effect size with SIBO as the outcome. Any selected genera were tested individually by Wilcoxon's rank-sum test to ensure that linear discriminant analysis effect size results were not outlier-skewed. RESULTS: Linear discriminant analysis effect size analysis identified Lactobacillus (linear discriminate analysis score, 4.59; P = .03) as over-represented in 15 out of the 90 children who were SIBO positive. CONCLUSIONS: These results suggest that glucose hydrogen breath test positivity in children from low-income settings may be due to an upper intestinal Lactobacillus bloom, potentially explaining the association of SIBO with the gut damage and inflammation that leads to malnutrition.

Using functional near-infrared spectroscopy to assess social information processing in poor urban Bangladeshi infants and toddlers.

Children living in low-resource settings are at risk for failing to reach their developmental potential. While the behavioral outcomes of growing up in such settings are well-known, the neural mechanisms underpinning poor outcomes have not been well elucidated, particularly in the context of low- and middle-income countries. In this study, we measure brain metabolic responses to social and nonsocial stimuli in a cohort of 6- and 36-month-old Bangladeshi children. Study participants in both cohorts lived in an urban slum and were exposed to a broad range of adversity early in life including extreme poverty, malnutrition, recurrent infections, and low maternal education. We observed brain regions that responded selectively to social stimuli in both ages indicating that these specialized brain responses are online from an early age. We additionally show that the magnitude of the socially selective response is related to maternal education, maternal stress, and the caregiving environment. Ultimately our results suggest that a variety of psychosocial hazards have a measurable relationship with the developing social brain.

Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children.

UNLABELLED: Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO's pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO's association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1ß (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation. IMPORTANCE: A total of 165 million children worldwide are considered stunted, which is associated with increased risk of death prior to age 5 years and cognitive disability. Stunting has, in part, been attributed to the presence of environmental enteropathy. Environmental enteropathy is a poorly understood condition leading to chronic intestinal inflammation. It has been postulated that small intestine bacterial overgrowth contributes to the pathogenesis of environmental enteropathy as overgrowth has been associated with intestinal inflammation and micronutrient malabsorption when it develops in other clinical contexts. This study confirms the finding that overgrowth occurs at high rates in the developing world. This is the first study to show that overgrowth is associated with intestinal inflammation and linear growth delay in this setting and is the first to examine why children with no known gastrointestinal dysfunction develop overgrowth from the developing world environment.