A methodological perspective on learning in the developing brain.

The brain undergoes profound development across childhood and adolescence, including continuous changes in brain morphology, connectivity, and functioning that are, in part, dependent on one's experiences. These neurobiological changes are accompanied by significant changes in children's and adolescents' cognitive learning. By drawing from studies in the domains of reading, reinforcement learning, and learning difficulties, we present a brief overview of methodological approaches and research designs that bridge brain- and behavioral research on learning. We argue that ultimately these methods and designs may help to unravel questions such as why learning interventions work, what learning computations change across development, and how learning difficulties are distinct between individuals.

Increased Ventromedial Prefrontal Cortex Activity in Adolescence Benefits Prosocial Reinforcement Learning.

Learning which of our behaviors benefit others contributes to forming social relationships. An important period for the development of (pro)social behavior is adolescence, which is characterized by transitions in social connections. It is, however, unknown how learning to benefit others develops across adolescence and what the underlying cognitive and neural mechanisms are. In this functional neuroimaging study, we assessed learning for self and others (i.e., prosocial learning) and the concurring neural tracking of prediction errors across adolescence (ages 9-21, N = 74). Participants performed a two-choice probabilistic reinforcement learning task in which outcomes resulted in monetary consequences for themselves, an unknown other, or no one. Participants from all ages were able to learn for themselves and others, but learning for others showed a more protracted developmental trajectory. Prediction errors for self were observed in the ventral striatum and showed no age-related differences. However, prediction error coding for others showed an age-related increase in the ventromedial prefrontal cortex. These results reveal insights into the computational mechanisms of learning for others across adolescence, and highlight that learning for self and others show different age-related patterns.

Developmental asymmetries in learning to adjust to cooperative and uncooperative environments.

Learning to successfully navigate social environments is a critical developmental goal, predictive of long-term wellbeing. However, little is known about how people learn to adjust to different social environments, and how this behaviour emerges across development. Here, we use a series of economic games to assess how children, adolescents, and young adults learn to adjust to social environments that differ in their level of cooperation (i.e., trust and coordination). Our results show an asymmetric developmental pattern: adjustment requiring uncooperative behaviour remains constant across adolescence, but adjustment requiring cooperative behaviour improves markedly across adolescence. Behavioural and computational analyses reveal that age-related differences in this social learning are shaped by age-related differences in the degree of inequality aversion and in the updating of beliefs about others. Our findings point to early adolescence as a phase of rapid change in cooperative behaviours, and highlight this as a key developmental window for interventions promoting well-adjusted social behaviour.

A three-wave longitudinal study of subcortical-cortical resting-state connectivity in adolescence: Testing age- and puberty-related changes.

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward-driven behavior. Although reward-driven behavior is supported by subcortical-medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting-state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three-wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self-reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age-related strengthening of subcortico-subcortical and cortico-cortical connectivity. Subcortical-cortical connectivity, such as, between the nucleus accumbens-frontal medial cortex, and the caudate-dorsal anterior cingulate cortex, however, weakened across age. Model-based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical-cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.

Representational similarity analysis offers a preview of the noradrenergic modulation of long-term fear memory at the time of encoding.

Neuroimaging research on emotional memory has greatly advanced our understanding of the pathogenesis of anxiety disorders. While the behavioral expression of fear at the time of encoding does not predict whether an aversive experience will evolve into long-term fear memory, the application of multi-voxel pattern analysis (MVPA) for the analysis of BOLD-MRI data has recently provided a unique marker for memory formation. Here, we aimed to further investigate the utility of this marker by modulating the strength of fear memory with an α2-adrenoceptor antagonist (yohimbine HCl). Fifty-two healthy participants were randomly assigned to two conditions - either receiving 20mg yohimbine or a placebo pill (double-blind) - prior to differential fear conditioning and MRI-scanning. We examined the strength of fear associations during acquisition and retention of fear (48 h later) by assessing the similarity of BOLD-MRI patterns and pupil dilation responses. Additionally, participants returned for a follow-up test outside the scanner (2-4 weeks), during which we assessed fear-potentiated startle responses. Replicating our previous findings, neural pattern similarity reflected the development of fear associations over time, and unlike average activation or pupil dilation, predicted the later expression of fear memory (pupil dilation 48 h later). While no effect of yohimbine was observed on markers of autonomic arousal, including salivary α-amylase (sAA), we obtained indirect evidence for the noradrenergic enhancement of fear memory consolidation: sAA levels showed a strong increase prior to fMRI scanning, irrespective of whether participants had received yohimbine, and this increase correlated with the subsequent expression of fear (48 h later). Remarkably, this noradrenergic enhancement of fear was associated with changes in neural response patterns at the time of learning. These findings provide further evidence that representational similarity analysis is a sensitive tool for studying (enhanced) memory formation.