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1.  Longitudinal Growth Curves of Brain Function Underlying Inhibitory Control through Adolescence 
The Journal of Neuroscience  2013;33(46):18109-18124.
Neuroimaging studies suggest that developmental improvements in inhibitory control are primarily supported by changes in prefrontal executive function. However, studies are contradictory with respect to how activation in prefrontal regions changes with age, and they have yet to analyze longitudinal data using growth curve modeling, which allows characterization of dynamic processes of developmental change, individual differences in growth trajectories, and variables that predict any interindividual variability in trajectories. In this study, we present growth curves modeled from longitudinal fMRI data collected over 302 visits (across ages 9 to 26 years) from 123 human participants. Brain regions within circuits known to support motor response control, executive control, and error processing (i.e., aspects of inhibitory control) were investigated. Findings revealed distinct developmental trajectories for regions within each circuit and indicated that a hierarchical pattern of maturation of brain activation supports the gradual emergence of adult-like inhibitory control. Mean growth curves of activation in motor response control regions revealed no changes with age, although interindividual variability decreased with development, indicating equifinality with maturity. Activation in certain executive control regions decreased with age until adolescence, and variability was stable across development. Error-processing activation in the dorsal anterior cingulate cortex showed continued increases into adulthood and no significant interindividual variability across development, and was uniquely associated with task performance. These findings provide evidence that continued maturation of error-processing abilities supports the protracted development of inhibitory control over adolescence, while motor response control regions provide early-maturing foundational capacities and suggest that some executive control regions may buttress immature networks as error processing continues to mature.
PMCID: PMC3828464  PMID: 24227721
2.  Sex differences in physiological reactivity to acute psychosocial stress in adolescence 
Psychoneuroendocrinology  2012;37(8):1135-1157.
Females begin to demonstrate greater negative affective responses to stress than males in adolescence. This may reflect the concurrent emergence of underlying differences in physiological response systems, including corticolimbic circuitries, the hypothalamic—pituitary— adrenal axis (HPAA), and the autonomic nervous system (ANS). This review examines when sex differences in physiological reactivity to acute psychosocial stress emerge and the directionality of these differences over development. Indeed, the literature indicates that sex differences emerge during adolescence and persist into adulthood for all three physiological response systems. However, the directionality of the differences varies by system. The emerging corti-colimbic reactivity literature suggests greater female reactivity, particularly in limbic regions densely innervated by gonadal hormone receptors. In contrast, males generally show higher levels of HPAA and ANS reactivity. We argue that the contrasting directionality of corticolimbic and peripheral physiological responses may reflect specific effects of gonadal hormones on distinct systems and also sex differences in evolved behavioral responses that demand different levels of peripheral physiological activation. Studies that examine both subjective reports of negative affect and physiological responses indicate that beginning in adolescence, females respond to acute stressors with more intense negative affect than males despite their comparatively lower peripheral physiological responses. This dissociation is not clearly explained by sex differences in the strength of the relationship between physiological and subjective responses. We suggest that females' greater subjective responsivity may instead arise from a greater activity in brain regions that translate stress responses to subjective awareness in adolescence. Future research directions include investigations of the role of pubertal hormones in physiological reactivity across all systems, examining the relationship of corticolimbic reactivity and negative affect, and sex differences in emotion regulation processes.
PMCID: PMC3472630  PMID: 22281210
Adolescent; Autonomic nervous system; Corticolimbic system; Hypothalamic—pituitary—adrenal axis; Sex differences; Psychosocial stress
3.  Developmental changes in brain function underlying the influence of reward processing on inhibitory control 
Adolescence is a period marked by changes in motivational and cognitive brain systems. However, the development of the interactions between reward and cognitive control processing are just beginning to be understood. Using event-related functional neuroimaging and an incentive modulated antisaccade task, we compared blood-oxygen level dependent activity underlying motivated response inhibition in children, adolescents, and adults. Behaviorally, children and adolescents performed significantly worse than adults during neutral trials. However, children and adolescents showed significant performance increases during reward trials. Adults showed no performance changes across conditions. fMRI results demonstrated that all groups recruited a similar circuitry to support task performance, including regions typically associated with rewards (striatum and orbital frontal cortex), and regions known to be involved in inhibitory control (putative frontal and supplementary eye fields, and posterior parietal cortex, and prefrontal loci). During rewarded trials adolescents showed increased activity in striatal regions, while adults demonstrated heightened activation in the OFC relative to children and adolescents. Children showed greater reliance on prefrontal executive regions that may be related to increased effort inhibiting responses. Overall, these results indicate that response inhibition is enhanced with reward contingencies over development. Adolescents’ heightened response in striatal regions may be one factor contributing to reward-biased decision making and perhaps risk taking behavior.
PMCID: PMC3181104  PMID: 21966352
adolescence; reward; inhibitory control; antisaccade; fMRI
4.  A Twin Study of Intracerebral Volumetric Relationships 
Behavior Genetics  2010;40(2):114-124.
Using high resolution magnetic resonance imaging data, we examined the interrelationships between eight cerebral lobar volumetric measures via both explor atory and confirmatory factor analyses in a large sample (N = 484) of pediatric twins and singletons. These analyses suggest the presence of strong genetic correlations between cerebral structures, particularly between regions of like tissue type or in spatial proximity. Structural modeling estimated that most of the variance in all structures is associated with highly correlated lobar latent factors, with differences in genetic covariance and heritability driven by a common genetic factor that influenced gray and white matter differently. Reanalysis including total brain volume as a covariate dramatically reduced the total residual variance and disproportionately influenced the additive genetic variance in all regions of interest.
PMCID: PMC3403699  PMID: 20112130
Twin; Cerebrum; MRI; Genetics; Pediatrics
5.  Effects of Response Preparation on Developmental Improvements in Inhibitory Control 
Acta psychologica  2010;134(3):253-263.
Studies in adults indicate that response preparation is crucial to inhibitory control, but it remains unclear whether preparation contributes to improvements in inhibitory control over the course of childhood and adolescence. In order to assess the role of response preparation in developmental improvements in inhibitory control, we parametrically manipulated the duration of the instruction period in an antisaccade (AS) task given to participants ages 8 to 31 years. Regressions showing a protracted development of AS performance were consistent with existing research, and two novel findings emerged. First, all participants showed improved performance with increased preparation time, indicating that response preparation is crucial to inhibitory control at all stages of development. Preparatory processes did not deteriorate at even the longest preparatory period, indicating that the youngest participants were able to sustain preparation at even the longest interval. Second, developmental trajectories did not differ for different preparatory period lengths, highlighting that the processes supporting response preparation continue to mature in tandem with improvements in AS performance. Our findings suggest that developmental improvements are not simply due to an inhibitory system that is faster to engage but may also reflect qualitative changes in the processes engaged during the preparatory period.
PMCID: PMC2885497  PMID: 20347061
response preparation; cognitive control; antisaccade; inhibitory control; development
6.  Variance Decomposition of MRI-Based Covariance Maps Using Genetically-Informative Samples and Structural Equation Modeling 
NeuroImage  2008;47(1):56-64.
The role of genetics in driving intracortical relationships is an important question that has rarely been studied in humans. In particular, there are no extant high-resolution imaging studies on genetic covariance. In this article, we describe a novel method that combines classical quantitative genetic methodologies for variance decomposition with recently-developed semi-multivariate algorithms for high-resolution measurement of phenotypic covariance. Using these tools, we produced correlational maps of genetic and environmental (i.e. nongenetic) relationships between several regions of interest and the cortical surface in a large pediatric sample of 600 twins, siblings, and singletons. These analyses demonstrated high, fairly uniform, statistically significant genetic correlations between the entire cortex and global mean cortical thickness. In agreement with prior reports on phenotypic covariance using similar methods, we found mean cortical thickness was most strongly correlated with association cortices. However, the present study suggests that genetics plays a large role in global brain patterning of cortical thickness in this manner. Further, using specific gyri with known high heritabilities as seed regions, we found a consistent pattern of high bilateral genetic correlations between structural homologues, with environmental correlations more restricted to the same hemisphere as the seed region, suggesting that interhemispheric covariance is largely genetically mediated. These findings are consistent with the limited existing knowledge on the genetics of cortical variability as well as our prior multivariate studies on cortical gyri.
PMCID: PMC2996833  PMID: 18672072
7.  Are There Differences in Brain Morphometry Between Twins and Unrelated Singletons? A Pediatric MRI Study 
Genes, brain, and behavior  2009;9(3):288-295.
Twins provide a unique capacity to explore relative genetic and environmental contributions to brain development, but results are applicable to non-twin populations only to the extent that twin and singleton brains are alike. A reason to suspect differences is that as a group twins are more likely than singletons to experience adverse prenatal and perinatal events that may affect brain development. We sought to assess whether this increased risk leads to differences in child or adolescent brain anatomy in twins who do not experience behavioral or neurological sequelae during the perinatal period. Brain MRI scans of 185 healthy pediatric twins (mean age=11.0, s.d.=3.6) were compared to scans of 167 age- and sex-matched unrelated singletons on brain structures measured, which included gray and white matter lobar volumes, ventricular volume, and area of the corpus callosum. There were no significant differences between groups for any structure, despite sufficient power for low Type II (i.e. false negative) error. The implications of these results are twofold: (1) within this age range and for these measures, it is appropriate to include healthy twins in studies of typical brain development, and (2) findings regarding heritability of brain structures obtained from twin studies can be generalized to non-twin populations.
PMCID: PMC2878374  PMID: 20100212
Twin; Singleton; Brain; Child; Adolescent

Results 1-7 (7)