Nancy L. Brodsky

Childhood poverty: specific associations with neurocognitive development.

Growing up in poverty is associated with reduced cognitive achievement as measured by standardized intelligence tests, but little is known about the underlying neurocognitive systems responsible for this effect. We administered a battery of tasks designed to tax-specific neurocognitive systems to healthy low and middle SES children screened for medical history and matched for age, gender and ethnicity. Higher SES was associated with better performance on the tasks, as expected, but the SES disparity was significantly nonuniform across neurocognitive systems. Pronounced differences were found in Left perisylvian/Language and Medial temporal/Memory systems, along with significant differences in Lateral/Prefrontal/Working memory and Anterior cingulate/Cognitive control and smaller, nonsignificant differences in Occipitotemporal/Pattern vision and Parietal/Spatial cognition.

Executive cognitive functions and impulsivity as correlates of risk taking and problem behavior in preadolescents

Initiation of drug use and other risky behavior in preadolescence is associated with poor developmental outcomes. In this research, we examine models that ascribe the trajectory to (a) weak executive cognitive function (ECF), (b) early manifestation of externalizing problems, or (c) heightened levels of trait impulsivity. We test the explanatory power of these factors in a structural equation model with a community sample of 387 preadolescents ages 10-12 years. Participants were tested with a computerized battery of tasks to assess three facets of ECF (working memory, cognitive control, and reward processing) as well as with an audio assisted computerized self-interview to obtain reports of impulsivity and risk behaviors (use of cigarettes and alcohol as well as engaging in fighting and gambling for money) and a self-administered questionnaire to assess externalizing and internalizing problems. The best fitting model explained both early risk taking and externalizing symptoms as the result of individual differences in impulsivity. Although no ECF was directly related to risk taking, working memory and one measure of reward processing performance (reversal learning) were inversely related to impulsivity. The results are discussed in regard to theories of early risk taking with particular focus on the potential relation between ECF and impulsive behavior tendencies and the implications for early intervention to prevent the dysfunctional trajectory associated with early risk behavior.

Early Parental Care Is Important for Hippocampal Maturation: Evidence from Brain Morphology in Humans

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Does adolescent risk taking imply weak executive function? A prospective study of relations between working memory performance, impulsivity, and risk taking in early adolescence.

Studies of brain development suggest that the increase in risk taking observed during adolescence may be due to insufficient prefrontal executive function compared to a more rapidly developing subcortical motivation system. We examined executive function as assessed by working memory ability in a community sample of youth (n = 387, ages 10 to 12 at baseline) in three annual assessments to determine its relation to two forms of impulsivity (sensation seeking and acting without thinking) and a wide range of risk and externalizing behavior. Using structural equation modeling, we tested a model in which differential activation of the dorsal and ventral striatum produces imbalance in the function of these brain regions. For youth high in sensation seeking, both regions were predicted to develop with age. However, for youth high in the tendency to act without thinking, the ventral striatum was expected to dominate. The model predicted that working memory ability would exhibit (1) early weakness in youth high in acting without thinking but (2) growing strength in those high in sensation seeking. In addition, it predicted that (3) acting without thinking would be more strongly related to risk and externalizing behavior than sensation seeking. Finally, it predicted that (4) controlling for acting without thinking, sensation seeking would predict later increases in risky and externalizing behavior. All four of these predictions were confirmed. The results indicate that the rise in sensation seeking that occurs during adolescence is not accompanied by a deficit in executive function and therefore requires different intervention strategies from those for youth whose impulsivity is characterized by early signs of acting without thinking.

Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile

Abstract Background: Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality. Objective: To determine if clinical characteristics, hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures. Design: The study was done in 2 phases. The first phase (S1) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset culture proven sepsis from 1991–1998. The second phase (S2) was a prospective study that enrolled infants ≥72 hours old, suspected of sepsis based on the presence of criteria identified in S1. At that time (day 0), blood was drawn for a CBC with differential, blood culture, IL-6 and IL-8 levels; cytokine levels were repeated on day 1. Infants with positive cultures were diagnosed as confirmed sepsis; those with negative cultures, as no sepsis. Results: S1: Of the 48 episodes of culture proven, late-onset sepsis, 54% of the blood cultures were positive by 24 hours and 90% by 48 hours. The most common presenting signs were desaturations (50%) and increased gastric residuals (33%); I/T ratio > 0.16 differentiated between gram-positive, negative and fungal infections (p = 0.007). S2: 27 infants were enrolled. Eight (mean [SEM] gestational age of 28.2 [0.94] weeks; birth weight of 1.15 [0.11] kg) had positive blood cultures; 19 (gestational age of 27.7 [0.9] weeks; birth weight of 1.06 [0.13] kg) had no sepsis. Infants with sepsis were more likely to have apnea/bradycardia (p = 0.002); no differences in hematological profile, as compared to those with no sepsis. Seven (88%) infants had positive blood cultures by 48 hours. Median values of IL-6 (pg/ml) were higher in infants with sepsis vs. those with no sepsis on days 0 [40 vs.13] (p = 0.03) and 1 [24 vs. 9] (p < 0.001). IL-8 levels were not significantly different. Conclusions. In both S1 and S2, a majority of the blood cultures were positive by 48 hours. IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis, prior to the blood culture being positive. IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis.

Working memory ability predicts trajectories of early alcohol use in adolescents: the mediational role of impulsivity

AIMS (i) To evaluate the role of pre-existing weakness in working memory ability (WM) as a risk factor for early alcohol use as mediated by different forms of impulsivity and (ii) to assess the adverse effects of progressive alcohol use on variations in WM over time. DESIGN, SETTING AND PARTICIPANTS A community sample of 358 adolescents [48% males, mean(age) (baseline) = 11.4 ± 0.87 years] from a longitudinal cohort design, assessed annually over 4 consecutive years with less than 6% attrition. MEASUREMENTS Repeated assessments were conducted for the following key variables: WM (based on performance on four separate tasks), frequency of alcohol use (AU) and three forms of impulsivity, namely sensation seeking (SS), acting without thinking (AWT) and delay discounting (DD). Latent growth curve modeling procedures were used to identify individual trajectories of change for all key variables. FINDINGS Weakness in WM (at baseline) predicted significantly both concurrent alcohol use and increased frequency of use over the four waves (P < 0.05). This effect was entirely mediated by two forms of impulsivity, AWT and DD, both of which were characterized by underlying weakness in WM. No individual variation was observed in the slopes of WM, which suggests that individual variations in alcohol use were not associated with changes in WM in our early adolescent sample. CONCLUSIONS Early adolescent alcohol use may be a consequence of (pre-existing) weaknesses in working memory (WM) rather than a cause of it. Efforts to reduce early alcohol use should consider the distinct roles of different impulsivity dimensions, in addition to WM, as potential targets of intervention.

A prospective comparison of developmental outcome of children with in utero cocaine exposure and controls using the Battelle Developmental Inventory.

Children with in utero cocaine exposure may be at risk for adverse neurodevelopmental outcome. To evaluate such outcome in young children, we administered the Battelle Developmental Inventory (BDI) to a group of inner-city children with (COC) and without (CON) in utero cocaine exposure at ages 3 and 5 years. Sixty-five COC and 68 CON, similar at age of testing, were evaluated at both time points by examiners masked to child group status. Both groups scored poorly and worsened over time. Although Total BDI raw scores were lower in the COC group than in the CON group at 3 years, this difference was related to postnatal environmental factors, caregiver (p = .022), and home environment (p = .010), not to in utero cocaine exposure (p = .88). At 5 years, the Total BDI score was related to the home environment (p < .001) but not to the caregiver (p = .36) or in utero cocaine exposure (p = .83). We conclude that inner-city children are at risk for adverse developmental outcome regardless of in utero cocaine exposure.

Neighborhood disadvantage and adolescent stress reactivity

Lower socioeconomic status (SES) is associated with higher levels of life stress, which in turn affect stress physiology. SES is related to basal cortisol and diurnal change, but it is not clear if SES is associated with cortisol reactivity to stress. To address this question, we examined the relationship between two indices of SES, parental education and concentrated neighborhood disadvantage, and the cortisol reactivity of African–American adolescents to a modified version of the Trier Social Stress Test (TSST). We found that concentrated disadvantage was associated with cortisol reactivity and this relationship was moderated by gender, such that higher concentrated disadvantage predicted higher cortisol reactivity and steeper recovery in boys but not in girls. Parental education, alone or as moderated by gender, did not predict reactivity or recovery, while neither education nor concentrated disadvantage predicted estimates of baseline cortisol. This finding is consistent with animal literature showing differential vulnerability, by gender, to the effects of adverse early experience on stress regulation and the differential effects of neighborhood disadvantage in adolescent males and females. This suggests that the mechanisms underlying SES differences in brain development and particularly reactivity to environmental stressors may vary across genders.

A prospective evaluation of early language development in children with in utero cocaine exposure and in control subjects

A cohort of children of low socioeconomic status, 76 with in utero cocaine exposure and 81 control subjects, was assessed for early language development at 2 1/2 years of age by a masked examiner using the Preschool Language Scale. There were no differences between groups in expressive, receptive, or total language score (all p > or = 0.57). Physicians caring for cocaine-exposed children with early language delay should not automatically ascribe the delay to cocaine exposure but should initiate a standard evaluation for language delay.

Site-specific characteristics of infants developing bronchopulmonary dysplasia.

Hypothesis:Site-specific variables that contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) can be identified.Objectives:To evaluate the demographic, nutrition and growth characteristics of infants at risk for developing BPD at two neonatal intensive care units (NICUs: sites A and O).Study Design:Records of 306 infants of <30 weeks gestational age (GA) who survived to at least 36 weeks postmenstrual age were retrospectively reviewed. Data were obtained for maternal and neonatal demographics, weights, total fluids, calories, carbohydrate, protein and fat intake at birth, 7, 14, 21 and 28 days of life.Results:BPD rates were not different at the two sites. No statistical differences were noted in the incidence of maternal chorioamnionitis, pregnancy-induced hypertension or use of antenatal steroids among infants who developed BPD (n=169) and those who did not (n=137). White race, birth weight, respiratory distress syndrome requiring surfactant, sepsis and patent ductus arteriosus were significantly associated (all P⩽0.03) with BPD. After controlling for significant confounding variables, infants who developed BPD had significantly (P<0.001) less weight gain, received less calories and fat in the first postnatal month. In the 26 to 28 weeks GA group, the odds of getting BPD were 5.4 (95%CI: 1.4 to 21.3) times greater for site A than site O (P=0.017).Conclusion:Our analysis suggests that while some decrease in BPD can be achieved by focusing on ventilation/oxygen use, this approach is unlikely to impact on the youngest infants.