Jamie L. Hanson

Early Stress Is Associated with Alterations in the Orbitofrontal Cortex: A Tensor-Based Morphometry Investigation of Brain Structure and Behavioral Risk

Individuals who experience early adversity, such as child maltreatment, are at heightened risk for a broad array of social and health difficulties. However, little is known about how this behavioral risk is instantiated in the brain. Here we examine a neurobiological contribution to individual differences in human behavior using methodology appropriate for use with pediatric populations paired with an in-depth measure of social behavior. We show that alterations in the orbitofrontal cortex among individuals who experienced physical abuse are related to social difficulties. These data suggest a biological mechanism linking early social learning to later behavioral outcomes.

Behavioral Problems After Early Life Stress: Contributions of the Hippocampus and Amygdala

BACKGROUND Early life stress (ELS) can compromise development, with higher amounts of adversity linked to behavioral problems. To understand this linkage, a growing body of research has examined two brain regions involved with socioemotional functioning-amygdala and hippocampus. Yet empirical studies have reported increases, decreases, and no differences within human and nonhuman animal samples exposed to different forms of ELS. This divergence in findings may stem from methodological factors, nonlinear effects of ELS, or both. METHODS We completed rigorous hand-tracing of the amygdala and hippocampus in three samples of children who experienced different forms of ELS (i.e., physical abuse, early neglect, or low socioeconomic status). Interviews were also conducted with children and their parents or guardians to collect data about cumulative life stress. The same data were also collected in a fourth sample of comparison children who had not experienced any of these forms of ELS. RESULTS Smaller amygdala volumes were found for children exposed to these different forms of ELS. Smaller hippocampal volumes were also noted for children who were physically abused or from low socioeconomic status households. Smaller amygdala and hippocampal volumes were also associated with greater cumulative stress exposure and behavioral problems. Hippocampal volumes partially mediated the relationship between ELS and greater behavioral problems. CONCLUSIONS This study suggests ELS may shape the development of brain areas involved with emotion processing and regulation in similar ways. Differences in the amygdala and hippocampus may be a shared diathesis for later negative outcomes related to ELS.

Family Poverty Affects the Rate of Human Infant Brain Growth

Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

Association of Child Poverty, Brain Development, and Academic Achievement

IMPORTANCE Children living in poverty generally perform poorly in school, with markedly lower standardized test scores and lower educational attainment. The longer children live in poverty, the greater their academic deficits. These patterns persist to adulthood, contributing to lifetime-reduced occupational attainment. OBJECTIVE To determine whether atypical patterns of structural brain development mediate the relationship between household poverty and impaired academic performance. DESIGN, SETTING, AND PARTICIPANTS Longitudinal cohort study analyzing 823 magnetic resonance imaging scans of 389 typically developing children and adolescents aged 4 to 22 years from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development with complete sociodemographic and neuroimaging data. Data collection began in November 2001 and ended in August 2007. Participants were screened for a variety of factors suspected to adversely affect brain development, recruited at 6 data collection sites across the United States, assessed at baseline, and followed up at 24-month intervals for a total of 3 periods. Each study center used community-based sampling to reflect regional and overall US demographics of income, race, and ethnicity based on the US Department of Housing and Urban Development definitions of area income. One-quarter of sample households reported the total family income below 200% of the federal poverty level. Repeated observations were available for 301 participants. EXPOSURE Household poverty measured by family income and adjusted for family size as a percentage of the federal poverty level. MAIN OUTCOMES AND MEASURES Childrens scores on cognitive and academic achievement assessments and brain tissue, including gray matter of the total brain, frontal lobe, temporal lobe, and hippocampus. RESULTS Poverty is tied to structural differences in several areas of the brain associated with school readiness skills, with the largest influence observed among children from the poorest households. Regional gray matter volumes of children below 1.5 times the federal poverty level were 3 to 4 percentage points below the developmental norm (P < .05). A larger gap of 8 to 10 percentage points was observed for children below the federal poverty level (P < .05). These developmental differences had consequences for childrens academic achievement. On average, children from low-income households scored 4 to 7 points lower on standardized tests (P < .05). As much as 20% of the gap in test scores could be explained by maturational lags in the frontal and temporal lobes. CONCLUSIONS AND RELEVANCE The influence of poverty on childrens learning and achievement is mediated by structural brain development. To avoid long-term costs of impaired academic functioning, households below 150% of the federal poverty level should be targeted for additional resources aimed at remediating early childhood environments.

Association between Income and the Hippocampus

Facets of the post-natal environment including the type and complexity of environmental stimuli, the quality of parenting behaviors, and the amount and type of stress experienced by a child affects brain and behavioral functioning. Poverty is a type of pervasive experience that is likely to influence biobehavioral processes because children developing in such environments often encounter high levels of stress and reduced environmental stimulation. This study explores the association between socioeconomic status and the hippocampus, a brain region involved in learning and memory that is known to be affected by stress. We employ a voxel-based morphometry analytic framework with region of interest drawing for structural brain images acquired from participants across the socioeconomic spectrum (n = 317). Children from lower income backgrounds had lower hippocampal gray matter density, a measure of volume. This finding is discussed in terms of disparities in education and health that are observed across the socioeconomic spectrum.

Structural Variations in Prefrontal Cortex Mediate the Relationship between Early Childhood Stress and Spatial Working Memory

A large corpus of research indicates that exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n = 61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence—a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning.

Blunted Ventral Striatum Development in Adolescence Reflects Emotional Neglect and Predicts Depressive Symptoms

BACKGROUND Emotional neglect is associated with multiple negative outcomes, particularly increased risk for depression. Motivated by increasing evidence of reward-related ventral striatum (VS) dysfunction in depression, we investigated the role of developmental changes in VS activity on the emergence of depressive symptomatology as a function of emotional neglect. METHODS We examined relationships between longitudinal neuroimaging of reward-related VS activity, assessments of mood, and measures of emotional neglect in 106 participants first scanned between ages 11 to 15 and then 2 years later. RESULTS We found that greater levels of emotional neglect were associated with blunted development of reward-related VS activity between the first and second assessments (as indexed by lower residualized change scores). Additionally, we found that decreases in this reward-related VS activity were related to greater depressive symptomatology and partially mediated the association between emotional neglect and subsequent depressive symptomatology. CONCLUSIONS Our results provide an important demonstration that blunted development of reward-related VS activity as a function of emotional neglect predicts the emergence of depressive symptoms in adolescents. Further, our results are consistent with emerging evidence for the importance of reward-related VS dysfunction in the etiology and pathophysiology of depression. These results are a first step toward developing the ability to predict, prevent, and treat stress-related psychopathology through the targeting of specific neural phenotypes.

Hormonal Reactivity to MRI Scanning in Adolescents

Magnetic resonance imaging (MRI) is a procedure that is now widely used to study emotional and cognitive processes in children and adolescents. However, the context within which brain imaging data are collected is a social context that may induce anxiety and stress. Several hormones have been shown to be responsive to environmental stressors. These stress responses may impact ability to successfully complete the procedure or collect imaging data. To investigate these issues, we measured salivary cortisol, dehydroepiandrosterone (DHEA), and testosterone in 160 adolescents during both a simulation (practice) and actual MRI. Hormones were all responsive to the MRI scan, indicating that an MRI scan itself can induce a stress response, with some hormones predicting the likelihood that an adolescent could successfully complete the scan with adequate data. The simulation scan did not hinder hormonal responses to the actual MRI. These data suggest that researchers should consider the effects of heightened hormonal reactivity to the scanning environment; adolescents reactions to brain imaging may contribute to image data loss and may potentially influence outcome measures.

Cumulative Stress In Childhood is Associated with Blunted Reward-Related Brain Activity In Adulthood

Early life stress (ELS) is strongly associated with negative outcomes in adulthood, including reduced motivation and increased negative mood. The mechanisms mediating these relations, however, are poorly understood. We examined the relation between exposure to ELS and reward-related brain activity, which is known to predict motivation and mood, at age 26, in a sample followed since kindergarten with annual assessments. Using functional neuroimaging, we assayed individual differences in the activity of the ventral striatum (VS) during the processing of monetary rewards associated with a simple card-guessing task, in a sample of 72 male participants. We examined associations between a cumulative measure of ELS exposure and VS activity in adulthood. We found that greater levels of cumulative stress during childhood and adolescence predicted lower reward-related VS activity in adulthood. Extending this general developmental pattern, we found that exposure to stress early in development (between kindergarten and grade 3) was significantly associated with variability in adult VS activity. Our results provide an important demonstration that cumulative life stress, especially during this childhood period, is associated with blunted reward-related VS activity in adulthood. These differences suggest neurobiological pathways through which a history of ELS may contribute to reduced motivation and increased negative mood.

Robust Automated Amygdala Segmentation via Multi-Atlas Diffeomorphic Registration

Here, we describe a novel method for volumetric segmentation of the amygdala from MRI images collected from 35 human subjects. This approach is adapted from open-source techniques employed previously with the hippocampus (Suh et al., 2011; Wang et al., 2011a,b). Using multi-atlas segmentation and machine learning-based correction, we were able to produce automated amygdala segments with high Dice (Mean = 0.918 for the left amygdala; 0.916 for the right amygdala) and Jaccard coefficients (Mean = 0.850 for the left; 0.846 for the right) compared to rigorously hand-traced volumes. This automated routine also produced amygdala segments with high intra-class correlations (consistency = 0.830, absolute agreement = 0.819 for the left; consistency = 0.786, absolute agreement = 0.783 for the right) and bivariate (r = 0.831 for the left; r = 0.797 for the right) compared to hand-drawn amygdala. Our results are discussed in relation to other cutting-edge segmentation techniques, as well as commonly available approaches to amygdala segmentation (e.g., Freesurfer). We believe this new technique has broad application to research with large sample sizes for which amygdala quantification might be needed.