vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development.

Neural correlates of expected risks and returns in risky choice across development.

Adolescence is often described as a period of increased risk taking relative to both childhood and adulthood. This inflection in risky choice behavior has been attributed to a neurobiological imbalance between earlier developing motivational systems and later developing top-down control regions. Yet few studies have decomposed risky choice to investigate the underlying mechanisms or tracked their differential developmental trajectory. The current study uses a risk-return decomposition to more precisely assess the development of processes underlying risky choice and to link them more directly to specific neural mechanisms. This decomposition specifies the influence of changing risks (outcome variability) and changing returns (expected value) on the choices of children, adolescents, and adults in a dynamic risky choice task, the Columbia Card Task. Behaviorally, risk aversion increased across age groups, with adults uniformly risk averse and adolescents showing substantial individual differences in risk sensitivity, ranging from risk seeking to risk averse. Neurally, we observed an adolescent peak in risk-related activation in the anterior insula and dorsal medial PFC. Return sensitivity, on the other hand, increased monotonically across age groups and was associated with increased activation in the ventral medial PFC and posterior cingulate cortex with age. Our results implicate adolescence as a developmental phase of increased neural risk sensitivity. Importantly, this work shows that using a behaviorally validated decision-making framework allows a precise operationalization of key constructs underlying risky choice that inform the interpretation of results.

Altered fear learning across development in both mouse and human.

The only evidence-based behavioral treatment for anxiety and stress-related disorders involves desensitization techniques that rely on principles of extinction learning. However, 40% of patients do not respond to this treatment. Efforts have focused on individual differences in treatment response, but have not examined when, during development, such treatments may be most effective. We examined fear-extinction learning across development in mice and humans. Parallel behavioral studies revealed attenuated extinction learning during adolescence. Probing neural circuitry in mice revealed altered synaptic plasticity of prefrontal cortical regions implicated in suppression of fear responses across development. The results suggest a lack of synaptic plasticity in the prefrontal regions, during adolescence, is associated with blunted regulation of fear extinction. These findings provide insight into optimizing treatment outcomes for when, during development, exposure therapies may be most effective.

Adolescent-specific patterns of behavior and neural activity during social reinforcement learning.

Humans are sophisticated social beings. Social cues from others are exceptionally salient, particularly during adolescence. Understanding how adolescents interpret and learn from variable social signals can provide insight into the observed shift in social sensitivity during this period. The present study tested 120 participants between the ages of 8 and 25 years on a social reinforcement learning task where the probability of receiving positive social feedback was parametrically manipulated. Seventy-eight of these participants completed the task during fMRI scanning. Modeling trial-by-trial learning, children and adults showed higher positive learning rates than did adolescents, suggesting that adolescents demonstrated less differentiation in their reaction times for peers who provided more positive feedback. Forming expectations about receiving positive social reinforcement correlated with neural activity within the medial prefrontal cortex and ventral striatum across age. Adolescents, unlike children and adults, showed greater insular activity during positive prediction error learning and increased activity in the supplementary motor cortex and the putamen when receiving positive social feedback regardless of the expected outcome, suggesting that peer approval may motivate adolescents toward action. While different amounts of positive social reinforcement enhanced learning in children and adults, all positive social reinforcement equally motivated adolescents. Together, these findings indicate that sensitivity to peer approval during adolescence goes beyond simple reinforcement theory accounts and suggest possible explanations for how peers may motivate adolescent behavior.

Curbing craving: behavioral and brain evidence that children regulate craving when instructed to do so but have higher baseline craving than adults.

Although one third of children and adolescents are overweight or obese, developmental changes in food craving and the ability to regulate craving remain poorly understood. We addressed this knowledge gap by examining behavioral and neural responses to images of appetizing unhealthy foods in individuals ages 6 through 23 years. On close trials (assessing unregulated craving), participants focused on a pictured food's appetitive features. On far trials (assessing effortful regulation), participants focused on a food's visual features and imagined that it was farther away. Across conditions, older age predicted less craving, less striatal recruitment, greater prefrontal activity, and stronger frontostriatal coupling. When effortfully regulating their responses to the images, all participants reported less craving and exhibited greater recruitment of lateral prefrontal cortex and less recruitment of ventromedial prefrontal cortex. Greater body mass predicted less regulation-related prefrontal activity, particularly among children. These results suggest that children experience stronger craving than adults but can also effectively regulate craving. Moreover, the mechanisms underlying regulation may differ for heavy and lean children.

The transition from childhood to adolescence is marked by a general decrease in amygdala reactivity and an affect-specific ventral-to-dorsal shift in medial prefrontal recruitment.

Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC), which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms.