Adriana Galván

Earlier Development of the Accumbens Relative to Orbitofrontal Cortex Might Underlie Risk-Taking Behavior in Adolescents

Adolescence has been characterized by risk-taking behaviors that can lead to fatal outcomes. This study examined the neurobiological development of neural systems implicated in reward-seeking behaviors. Thirty-seven participants (7–29 years of age) were scanned using event-related functional magnetic resonance imaging and a paradigm that parametrically manipulated reward values. The results show exaggerated accumbens activity, relative to prefrontal activity in adolescents, compared with children and adults, which appeared to be driven by different time courses of development for these regions. Accumbens activity in adolescents looked like that of adults in both extent of activity and sensitivity to reward values, although the magnitude of activity was exaggerated. In contrast, the extent of orbital frontal cortex activity in adolescents looked more like that of children than adults, with less focal patterns of activity. These findings suggest that maturing subcortical systems become disproportionately activated relative to later maturing top–down control systems, biasing the adolescents action toward immediate over long-term gains.

Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task

BACKGROUND Adolescence is a transition period from childhood to adulthood that is often characterized by emotional instability. This period is also a time of increased incidence of anxiety and depression, underscoring the importance of understanding biological substrates of behavioral and emotion regulation during adolescence. Developmental changes in the brain in concert with individual predispositions for anxiety might underlie the increased risk for poor outcomes reported during adolescence. We tested the hypothesis that difficulties in regulating behavior in emotional contexts in adolescents might be due to competition between heightened activity in subcortical emotional processing systems and immature top-down prefrontal systems. Individual differences in emotional reactivity might put some teens at greater risk during this sensitive transition in development. METHODS We examined the association between emotion regulation and frontoamygdala circuitry in 60 children, adolescents, and adults with an emotional go-nogo paradigm. We went beyond examining the magnitude of neural activity and focused on neural adaptation within this circuitry across time with functional magnetic resonance imaging. RESULTS Adolescents showed exaggerated amygdala activity relative to children and adults. This age-related difference decreased with repeated exposures to the stimuli, and individual differences in self-ratings of anxiety predicted the extent of adaptation or habituation in amygdala. Individuals with higher trait anxiety showed less habituation over repeated exposures. This failure to habituate was associated with less functional connectivity between ventral prefrontal cortex and amygdala. CONCLUSIONS These findings suggest that exaggerated emotional reactivity during adolescence might increase the need for top-down control and put individuals with less control at greater risk for poor outcomes.

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Changes in cerebral functional organization during cognitive development

It has been just under a decade since contemporary neuroimaging tools, such as functional magnetic resonance imaging, were first applied to developmental questions. These tools provide invaluable information on how brain anatomy, function and connectivity change during development. Studies using these methods with children and adolescents show that brain regions that support motor and sensory function mature earliest, whereas higher-order association areas, such as the prefrontal cortex, which integrate these functions, mature later.

Adolescent development of the reward system

Adolescence is a developmental period characterized by increased reward-seeking behavior. Investigators have used functional magnetic resonance imaging (fMRI) in conjunction with reward paradigms to test two opposing hypotheses about adolescent developmental changes in the striatum, a region implicated in reward processing. One hypothesis posits that the striatum is relatively hypo-responsive to rewards during adolescence, such that heightened reward-seeking behavior is necessary to achieve the same activation as adults. Another view suggests that during adolescence the striatal reward system is hyper-responsive, which subsequently results in greater reward-seeking. While evidence for both hypotheses has been reported, the field has generally converged on this latter hypothesis based on compelling evidence. In this review, I describe the evidence to support this notion, speculate on the disparate fMRI findings and conclude with future areas of inquiry to this fascinating question.

Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls

Genetic influences on behavior are complex and, as such, the effect of any single gene is likely to be modest. Neuroimaging measures may serve as a biological intermediate phenotype to investigate the effect of genes on human behavior. In particular, it is possible to constrain investigations by prior knowledge of gene characteristics and by including samples of subjects where the distribution of phenotypic variance is both wide and under heritable influences. Here, we use this approach to show a dissociation between the effects of two dopamine genes that are differentially expressed in the brain. We show that the DAT1 gene, a gene expressed predominantly in the basal ganglia, preferentially influences caudate volume, whereas the DRD4 gene, a gene expressed predominantly in the prefrontal cortex, preferentially influences prefrontal gray matter volume in a sample of subjects including subjects with ADHD, their unaffected siblings, and healthy controls. This demonstrates that, by constraining our investigations by prior knowledge of gene expression, including samples in which the distribution of phenotypic variance is wide and under heritable influences, and by using intermediate phenotypes, such as neuroimaging, we may begin to map out the pathways by which genes influence behavior.

The role of ventral frontostriatal circuitry in reward-based learning in humans.

This study examined changes in behavior and neural activity with reward learning. Using an event-related functional magnetic resonance imaging paradigm, we show that the nucleus accumbens, thalamus, and orbital frontal cortex are each sensitive to reward magnitude, with the accumbens showing the greatest discrimination between reward values. Mean reaction times were significantly faster to cues predicting the greatest reward and slower to cues predicting the smallest reward. This behavioral change over the course of the experiment was paralleled by a shift in peak in accumbens activity from anticipation of the reward (immediately after the response), to the cue predicting the reward. The orbitofrontal and thalamic regions peaked in anticipation of the reward throughout the experiment. Our findings suggest discrete functions of regions within basal ganglia thalamocortical circuitry in adjusting behavior to maximize reward.

Engagement of large-scale networks is related to individual differences in inhibitory control.

Understanding which brain regions regulate the execution, and suppression, of goal-directed behavior has implications for a number of areas of research. In particular, understanding which brain regions engaged during tasks requiring the execution and inhibition of a motor response provides insight into the mechanisms underlying individual differences in response inhibition ability. However, neuroimaging studies examining the relation between activation and stopping have been inconsistent regarding the direction of the relationship, and also regarding the anatomical location of regions that correlate with behavior. These limitations likely arise from the relatively low power of voxelwise correlations with small sample sizes. Here, we pooled data over five separate fMRI studies of the Stop-signal task in order to obtain a sufficiently large sample size to robustly detect brain/behavior correlations. In addition, rather than performing mass univariate correlation analysis across all voxels, we increased statistical power by reducing the dimensionality of the data set using independent component analysis and then examined correlations between behavior and the resulting component scores. We found that components reflecting activity in regions thought to be involved in stopping were associated with better stopping ability, while activity in a default-mode network was associated with poorer stopping ability across individuals. These results clearly show a relationship between individual differences in stopping ability in specific activated networks, including regions known to be critical for the behavior. The results also highlight the usefulness of using dimensionality reduction to increase the power to detect brain/behavior correlations in individual differences research.

The effects of poor quality sleep on brain function and risk taking in adolescence.

Insufficient sleep and poor quality sleep are pervasive during adolescence and relate to impairments in cognitive control and increased risk taking. However, the neurobiology underlying the association between sleep and adolescent behavior remains elusive. In the current study, we examine how poor sleep quality relates to cognitive control and reward related brain function during risk taking. Forty-six adolescents participated in a functional magnetic imaging (fMRI) scan during which they completed a cognitive control and risk taking task. Behaviorally, adolescents who reported poorer sleep also exhibited greater risk-taking. This association was paralleled by less recruitment of the dorsolateral prefrontal cortex (DLPFC) during cognitive control, greater insula activation during reward processing, and reduced functional coupling between the DLPFC and affective regions including the insula and ventral striatum during reward processing. Collectively, these results suggest that poor sleep may exaggerate the normative imbalance between affective and cognitive control systems, leading to greater risk-taking in adolescents.

Measurement and Reliability of Response Inhibition

Response inhibition plays a critical role in adaptive functioning and can be assessed with the Stop-signal task, which requires participants to suppress prepotent motor responses. Evidence suggests that this ability to inhibit a prepotent motor response (reflected as Stop-signal reaction time (SSRT)) is a quantitative and heritable measure of interindividual variation in brain function. Although attention has been given to the optimal method of SSRT estimation, and initial evidence exists in support of its reliability, there is still variability in how Stop-signal task data are treated across samples. In order to examine this issue, we pooled data across three separate studies and examined the influence of multiple SSRT calculation methods and outlier calling on reliability (using Intra-class correlation). Our results suggest that an approach which uses the average of all available sessions, all trials of each session, and excludes outliers based on predetermined lenient criteria yields reliable SSRT estimates, while not excluding too many participants. Our findings further support the reliability of SSRT, which is commonly used as an index of inhibitory control, and provide support for its continued use as a neurocognitive phenotype.