Sabine Peters

Testing a dual-systems model of adolescent brain development using resting-state connectivity analyses

The current study aimed to test a dual-systems model of adolescent brain development by studying changes in intrinsic functional connectivity within and across networks typically associated with cognitive-control and affective-motivational processes. To this end, resting-state and task-related fMRI data were collected of 269 participants (ages 8-25). Resting-state analyses focused on seeds derived from task-related neural activation in the same participants: the dorsal lateral prefrontal cortex (dlPFC) from a cognitive rule-learning paradigm and the nucleus accumbens (NAcc) from a reward-paradigm. Whole-brain seed-based resting-state analyses showed an age-related increase in dlPFC connectivity with the caudate and thalamus, and an age-related decrease in connectivity with the (pre)motor cortex. nAcc connectivity showed a strengthening of connectivity with the dorsal anterior cingulate cortex (ACC) and subcortical structures such as the hippocampus, and a specific age-related decrease in connectivity with the ventral medial PFC (vmPFC). Behavioral measures from both functional paradigms correlated with resting-state connectivity strength with their respective seed. That is, age-related change in learning performance was mediated by connectivity between the dlPFC and thalamus, and age-related change in winning pleasure was mediated by connectivity between the nAcc and vmPFC. These patterns indicate (i) strengthening of connectivity between regions that support control and learning, (ii) more independent functioning of regions that support motor and control networks, and (iii) more independent functioning of regions that support motivation and valuation networks with age. These results are interpreted vis-à-vis a dual-systems model of adolescent brain development.

The link between testosterone and amygdala–orbitofrontal cortex connectivity in adolescent alcohol use

Alcohol consumption is one of the most problematic and widespread forms of risk taking in adolescence. It has been hypothesized that sex hormones such as testosterone play an important role in risk taking by influencing the development of brain networks involved in emotion and motivation, particularly the amygdala and its functional connections. Connectivity between the amygdala and the orbitofrontal cortex (OFC) may be specifically related to alcohol use, given the association of this tract with top-down control over behavioral approach tendencies. In line with this, prior studies in adults indicate a link between alcohol use and functional connectivity between the amygdala and the orbitofrontal cortex (OFC), as well as between testosterone and amygdala-OFC connectivity. We consolidated these research lines by investigating the association between alcohol use, testosterone and resting state functional brain connectivity within one large-scale adolescent sample (n=173, aged 12-25 years). Mediation analyses demonstrated an indirect effect of testosterone levels on alcohol use through amygdala-OFC intrinsic functional connectivity, but only in boys. That is, increased testosterone in boys was associated with reduced amygdala-OFC connectivity, which in turn was associated with increased alcohol intake. This study is the first to demonstrate the interplay between adolescent alcohol use, sex hormones and brain mechanisms, thus taking an important step to increase our understanding of the mechanisms behind this form of adolescent risk-taking.

The neural coding of feedback learning across child and adolescent development

The ability to learn from environmental cues is an important contributor to successful performance in a variety of settings, including school. Despite the progress in unraveling the neural correlates of cognitive control in childhood and adolescence, relatively little is known about how these brain regions contribute to learning. In this study, 268 participants aged 8–25 years performed a rule-learning task with performance feedback in a 3T MRI scanner. We examined the development of the frontoparietal network during feedback learning by exploring contributions of age and pubertal development. The pFC showed more activation following negative compared with positive feedback with increasing age. In contrast, our data suggested that the parietal cortex demonstrated a shift from sensitivity to positive feedback in young children to negative feedback in adolescents and adults. These findings were interpreted in terms of separable contributions of the frontoparietal network in childhood to more integrated functions in adulthood. Puberty (testosterone, estradiol, and self-report) did not explain additional variance in neural activation patterns above age, suggesting that development of the frontoparietal network occurs relatively independently from hormonal development. This study presents novel insights into the development of learning, moving beyond a simple frontoparietal immaturity hypothesis.

What motivates adolescents? Neural responses to rewards and their influence on adolescents' risk taking, learning, and cognitive control

Adolescence is characterized by pronounced changes in motivated behavior, during which emphasis on potential rewards may result in an increased tendency to approach things that are novel and bring potential for positive reinforcement. While this may result in risky and health-endangering behavior, it may also lead to positive consequences, such as behavioral flexibility and greater learning. In this review we will discuss both the maladaptive and adaptive properties of heightened reward-sensitivity in adolescents by reviewing recent cognitive neuroscience findings in relation to behavioral outcomes. First, we identify brain regions involved in processing rewards in adults and adolescents. Second, we discuss how functional changes in reward-related brain activity during adolescence are related to two behavioral domains: risk taking and cognitive control. Finally, we conclude that progress lies in new levels of explanation by further integration of neural results with behavioral theories and computational models. In addition, we highlight that longitudinal measures, and a better conceptualization of adolescence and environmental determinants, are of crucial importance for understanding positive and negative developmental trajectories.

Nucleus accumbens response to rewards and testosterone levels are related to alcohol use in adolescents and young adults

During adolescence there is a normative increase in risk-taking behavior, which is reflected in, for example, increases in alcohol consumption. Prior research has demonstrated a link between testosterone and alcohol consumption, and between testosterone and neural responses to rewards. Yet, no study to date tested how testosterone levels and neural responses to rewards relate to and predict individual differences in alcohol use. The current study aimed to investigate this by assessing alcohol use, testosterone levels and neural responses to rewards in adolescents (12–17 years old) and young adults (18–26 years old). Participants were measured twice with a two-year interval between testing sessions. Cross-sectional analysis showed that at the second time point higher neural activity to rewards, but not testosterone levels, explained significant variance above age in reported alcohol use. Predictive analyses showed that, higher testosterone level at the first time point, but not neural activity to rewards at the first time point, was predictive of more alcohol use at the second time point. These results suggest that neural responses to rewards are correlated with current alcohol consumption, and that testosterone level is predictive of future alcohol consumption. These results are interpreted in the context of trajectory models of adolescent development.

Strategies influence neural activity for feedback learning across child and adolescent development

Learning from feedback is an important aspect of executive functioning that shows profound improvements during childhood and adolescence. This is accompanied by neural changes in the feedback-learning network, which includes pre-supplementary motor area (pre- SMA)/anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), superior parietal cortex (SPC), and the basal ganglia. However, there can be considerable differences within age ranges in performance that are ascribed to differences in strategy use. This is problematic for traditional approaches of analyzing developmental data, in which age groups are assumed to be homogenous in strategy use. In this study, we used latent variable models to investigate if underlying strategy groups could be detected for a feedback-learning task and whether there were differences in neural activation patterns between strategies. In a sample of 268 participants between ages 8 to 25 years, we observed four underlying strategy groups, which were cut across age groups and varied in the optimality of executive functioning. These strategy groups also differed in neural activity during learning; especially the most optimal performing group showed more activity in DLPFC, SPC and pre-SMA/ACC compared to the other groups. However, age differences remained an important contributor to neural activation, even when correcting for strategy. These findings contribute to the debate of age versus performance predictors of neural development, and highlight the importance of studying individual differences in strategy use when studying development.

Longitudinal development of frontoparietal activity during feedback learning: Contributions of age, performance, working memory and cortical thickness

Highlights • We performed a longitudinal study on feedback learning (N = 208, age 8–27 years).• We tested linear and nonlinear patterns in frontoparietal activity during learning.• DLPFC and parietal cortex showed a late-adolescent peak in activity.• SMA showed a linear increase, and ACC a linear decrease in brain activity with age.• Performance predicted DLPFC and parietal activity, thickness predicted SMA activity.

Emotional reactions of peers influence decisions about fairness in adolescence

During adolescence, peers take on increasing importance, while social skills are still developing. However, how emotions of peers influence social decisions during that age period is insufficiently known. We therefore examined the effects of three different emotional responses (anger, disappointment, happiness) on decisions about fairness in a sample of 156 adolescents aged 12–17 years. Participants received written emotional responses from peers in a version of the Dictator Game to a previous unfair offer. Adolescents reacted with more generous offers after disappointed reactions compared to angry and happy reactions. Furthermore, we found preliminary evidence for developmental differences over adolescence, since older adolescents differentiated more between the three emotions than younger adolescents. In addition, individual differences in social value orientation played a role in decisions after happy reactions of peers to a previous unfair offer, such that participants with a “proself” orientation made more unfair offers to happy peers than “prosocial” participants. Taken together, our findings demonstrate that adolescents take emotions of peers into account when making social decisions, while individual differences in social value orientation affect these decisions, and age seems to influence the nature of the reaction.

Longitudinal development of hippocampal subregions from childhood to adulthood

Highlights • Hippocampal subregions develop in differential ways from childhood to adulthood.• Subiculum, CA1, ML and fimbria showed nonlinear trajectories with initial increases.• Parasubiculum, presubiculum, CA2/3, CA4 and GC-DG showed linear volume decreases.• There were no sex differences in hippocampal subregion development.• General cognitive ability associated with CA2/3 and CA4 volumes and ML development.

Emerging depression in adolescence coincides with accelerated frontal cortical thinning

Background Adolescence is a transition period characterized by heightened emotional reactivity, which for some sets the stage for emerging depressive symptoms. Prior studies suggest that adolescent depression is associated with deviant cortical and subcortical brain structure. Longitudinal studies are, however, currently scarce, but critical to detect which adolescents are at risk for developing depressive symptoms. Methods In this longitudinal study, a community sample of 205 participants underwent magnetic resonance imaging (MRI) in three biennial waves (522 scans) spanning 5 years across ages 8–25 years. Depressive symptomatology was assessed using self‐report at the third time point. Mixed models were used to examine the relations between structural brain development, specifically regional change in cortical thickness, surface area and subcortical volumes (hippocampus and amygdala), and depressive symptoms. Results Accelerated frontal lobe cortical thinning was observed in adolescents who developed depressive symptoms at the third time point. This effect remained after controlling for parent‐reported affective problems at the first time point. Moreover, the effect was driven by specific lateral orbitofrontal and precentral regions. In addition, differential developmental trajectories of parietal cortical thickness and surface area in several regions were found for participants reporting higher depressive symptomatology, but these results did not survive correction for multiple comparisons. Volumes or developmental volume changes in hippocampus or amygdala were not related to depressive symptoms. Conclusions This study showed that emerging depression is associated with cortical thinning in frontal regions within individuals. These findings move beyond detecting cross‐sectional correlations and set the stage for early detection, which may inform future intervention.