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    Article: Variation in neural development as a result of exposure to institutionalization early in childhood.
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    ABSTRACT: We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania (n = 20), children exposed to institutional rearing (n = 29), and children previously exposed to institutional rearing but then randomized to a high-quality foster care intervention (n = 25). In so doing, we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure, using data from the only existing randomized controlled trial of foster care for institutionalized children. Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol. Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children. Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not randomized to foster care. We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data. As hypothesized, the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not randomized to foster care. The increase in white matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental "catch up" in white matter growth, even following extreme environmental deprivation.
    Proceedings of the National Academy of Sciences 07/2012; 109(32):12927-32. · 9.68 Impact Factor
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    Article: The impact of social disparity on prefrontal function in childhood.
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    ABSTRACT: The prefrontal cortex (PFC) develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES) and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children.
    PLoS ONE 01/2012; 7(4):e35744. · 4.09 Impact Factor
  • Article: Longitudinal evidence for functional specialization of the neural circuit supporting working memory in the human brain.
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    ABSTRACT: Although children perform more poorly than adults on many cognitive measures, they are better able to learn things such as language and music. These differences could result from the delayed specialization of neural circuits and asynchronies in the maturation of neural substrates required for learning. Working memory--the ability to hold information in mind that is no longer present in the environment--comprises a set of cognitive processes required for many, if not all, forms of learning. A critical neural substrate for working memory (the prefrontal cortex) continues to mature through early adulthood. What are the functional consequences of this late maturation for working memory? Using a longitudinal design, we show that although individuals recruit prefrontal cortex as expected during both early and late adolescence during a working memory task, this recruitment is correlated with behavior only in late adolescence. The hippocampus is also recruited, but only during early, and not late, adolescence. Moreover, the hippocampus and prefrontal cortex are coactive in early adolescence regardless of task demands or performance, in contrast to the pattern seen in late adolescents and adults, when these regions are coactive only under high task demands. Together, these data demonstrate that neural circuitry underlying working memory changes during adolescent development. The diminishing contribution of the hippocampus in working memory function with age is an important observation that informs questions about how children and adults learn differently.
    Journal of Neuroscience 08/2010; 30(33):11062-7. · 7.11 Impact Factor
  • Article: Stimulant medication and prefrontal functional connectivity during working memory in ADHD: a preliminary report.
    Margaret A Sheridan, Stephen Hinshaw, Mark D'Esposito
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    ABSTRACT: Recent theoretical and empirical work suggests that while unmedicated, children with ADHD have a deficit in subcortical processing that leads to greater and more varied prefrontal cortical (PFC) activation, compared to (a) age-matched control participants and (b) their own brain activity while on stimulant medication. This pattern has been described elsewhere as inefficient. Functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used during a working memory task for five female adolescents with ADHD, aged 11 to 17 years, both on and off their usual dose of stimulant medication. On medication, adolescents with ADHD demonstrated less PFC activation and less functional connectivity between frontal and subcortical regions compared to off medication. Because of the small sample size, results are presented as preliminary findings which await replication in a larger sample. However, these findings lend support to the idea that remediation of inefficiencies in PFC function for individuals with ADHD by stimulant medication may be related, in part, to frontal-subcortical connectivity.
    Journal of Attention Disorders 07/2010; 14(1):69-78. · 2.45 Impact Factor
  • Article: Delayed maturation in brain electrical activity partially explains the association between early environmental deprivation and symptoms of attention-deficit/hyperactivity disorder.
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    ABSTRACT: Children raised in institutional settings are exposed to social and environmental circumstances that may deprive them of expected environmental inputs during sensitive periods of brain development that are necessary to foster healthy development. This deprivation is thought to underlie the abnormalities in neurodevelopment that have been found in previously institutionalized children. It is unknown whether deviations in neurodevelopment explain the high rates of developmental problems evident in previously institutionalized children, including psychiatric disorders. We present data from a sample of children raised in institutions in Bucharest, Romania (n = 117) and an age- and sex-matched sample of community control subjects (n = 49). Electroencephalogram data were acquired following entry into the study at age 6 to 30 months, and a structured diagnostic interview of psychiatric disorders was completed at age 54 months. Children reared in institutions evidenced greater symptoms of attention-deficit/hyperactivity disorder, anxiety, depression, and disruptive behavior disorders than community controls. Electroencephalogram revealed significant reductions in alpha relative power and increases in theta relative power among children reared in institutions in frontal, temporal, and occipital regions, suggesting a delay in cortical maturation. This pattern of brain activity predicted symptoms of hyperactivity and impulsivity at age 54 months, and significantly mediated the association between institutionalization and attention-deficit/hyperactivity disorder symptoms. Electroencephalogram power was unrelated to depression, anxiety, or disruptive behaviors. These findings document a potential neurodevelopmental mechanism underlying the association between institutionalization and psychiatric morbidity. Deprivation in social and environmental conditions may perturb early patterns of neurodevelopment and manifest as psychiatric problems later in life.
    Biological psychiatry 05/2010; 68(4):329-36. · 8.93 Impact Factor

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