Reward Enhances Memory via Age-Varying Online and Offline Neural Mechanisms across Development.

Reward motivation enhances memory through interactions between mesolimbic, hippocampal, and cortical systems, both during and after encoding. Developmental changes in these distributed neural circuits may lead to age-related differences in reward-motivated memory and the underlying neural mechanisms. Converging evidence from cross-species studies suggests that subcortical dopamine signaling is increased during adolescence, which may lead to stronger memory representations of rewarding, relative to mundane, events and changes in the contributions of underlying subcortical and cortical brain mechanisms across age. Here, we used fMRI to examine how reward motivation influences the "online" encoding and "offline" postencoding brain mechanisms that support long-term associative memory from childhood to adulthood in human participants of both sexes. We found that reward motivation led to both age-invariant enhancements and nonlinear age-related differences in associative memory after 24 h. Furthermore, reward-related memory benefits were linked to age-varying neural mechanisms. During encoding, interactions between the prefrontal cortex (PFC) and ventral tegmental area (VTA) were associated with better high-reward memory to a greater degree with increasing age. Preencoding to postencoding changes in functional connectivity between the anterior hippocampus and VTA were also associated with better high-reward memory, but more so at younger ages. Our findings suggest that there may be developmental differences in the contributions of offline subcortical and online cortical brain mechanisms supporting reward-motivated memory.SIGNIFICANCE STATEMENT A substantial body of research has examined the neural mechanisms through which reward influences memory formation in adults. However, despite extensive evidence that both reward processing and associative memory undergo dynamic change across development, few studies have examined age-related changes in these processes. We found both age-invariant and nonlinear age-related differences in reward-motivated memory. Moreover, our findings point to developmental differences in the processes through which reward modulates the prioritization of information in long-term memory, with greater early reliance on offline subcortical consolidation mechanisms and increased contribution of systems-level online encoding circuitry with increasing age. These results highlight dynamic developmental changes in the cognitive and neural mechanisms through which motivationally salient information is prioritized in memory from childhood to adulthood.

Uncertain threat is associated with greater impulsive actions and neural dissimilarity to Black versus White faces.

Race is a social construct that contributes to group membership and heightens emotional arousal in intergroup contexts. Little is known about how emotional arousal, specifically uncertain threat, influences behavior and brain processes in response to race information. We investigated the effects of experimentally manipulated uncertain threat on impulsive actions to Black versus White faces in a community sample (n = 106) of Black and White adults. While undergoing fMRI, participants performed an emotional go/no-go task under three conditions of uncertainty: 1) anticipation of an uncertain threat (i.e., unpredictable loud aversive sound); 2) anticipation of an uncertain reward (i.e., unpredictable receipt of money); and 3) no anticipation of an uncertain event. Representational similarity analysis was used to examine the neural representations of race information across functional brain networks between conditions of uncertainty. Participants-regardless of their own race-showed greater impulsivity and neural dissimilarity in response to Black versus White faces across all functional brain networks in conditions of uncertain threat relative to other conditions. This pattern of greater neural dissimilarity under threat was enhanced in individuals with high implicit racial bias. Our results illustrate the distinct and important influence of uncertain threat on global differentiation in how race information is represented in the brain, which may contribute to racially biased behavior.

Reward-motivated memories influence new learning across development.

Previously rewarding experiences can influence choices in new situations. Past work has demonstrated that existing reward associations can either help or hinder future behaviors and that there is substantial individual variability in the transfer of value across contexts. Developmental changes in reward sensitivity may also modulate the impact of prior reward associations on later goal-directed behavior. The current study aimed to characterize how reward associations formed in the past affected learning in the present from childhood to adulthood. Participants completed a reinforcement learning paradigm using high- and low-reward stimuli from a task completed 24 h earlier, as well as novel stimuli, as choice options. We found that prior high-reward associations impeded learning across all ages. We then assessed how individual differences in the prioritization of high- versus low-reward associations in memory impacted new learning. Greater high-reward memory prioritization was associated with worse learning performance for previously high-reward relative to low-reward stimuli across age. Adolescents also showed impeded early learning regardless of individual differences in high-reward memory prioritization. Detrimental effects of previous reward on choice behavior did not persist beyond learning. These findings indicate that prior reward associations proactively interfere with future learning from childhood to adulthood and that individual differences in reward-related memory prioritization influence new learning across age.

Adolescent-specific memory effects: evidence from working memory, immediate and long-term recognition memory performance in 8-30 yr olds.

Working memory and recognition memory develop across adolescence, but the relationship between them is not fully understood. We investigated associations between n-back task performance and subsequent recognition memory in a community sample (8-30 yr, n = 150) using tasks from the Adolescent Brain Cognitive Development Study (ABCD Study) to cross-sectionally assess memory in an age range that will be sampled longitudinally. We added a 24-h delay condition to assess long-term recognition. Overall working memory, immediate and long-term recognition performance peaked in adolescence. Age effects in recognition memory varied by items (old targets, old distractors, and new items) and delay (0 and 24 h). For immediate recognition, accuracy was higher for targets and new items than for distractors, with accuracy for targets peaking in adulthood and accuracy for new items peaking during adolescence. For long-term recognition, adolescents' accuracy was higher for targets than distractors, while adults showed similarly high accuracy for targets and distractors and children showed low accuracy for both. This pattern appeared to be specific to recognition of items from the high working memory load condition. The results suggest that working memory may facilitate long-term recognition of task-relevant over irrelevant items and may benefit the detection of new information during adolescence.

Real-World Exploration Increases Across Adolescence and Relates to Affect, Risk Taking, and Social Connectivity.

Cross-species research suggests that exploratory behaviors increase during adolescence and relate to the social, affective, and risky behaviors characteristic of this developmental stage. However, how these typical adolescent behaviors manifest and relate in real-world settings remains unclear. Using geolocation tracking to quantify exploration-variability in daily movement patterns-over a 3-month period in 58 adolescents and adults (ages 13-27) in New York City, we investigated whether daily exploration varied with age and whether exploration related to social connectivity, risk taking, and momentary positive affect. In our cross-sectional sample, we found an association between daily exploration and age, with individuals near the transition to legal adulthood exhibiting the highest exploration levels. Days of higher exploration were associated with greater positive affect irrespective of age. Higher mean exploration was associated with greater social connectivity in all participants but was linked to higher risk taking selectively among adolescents. Our results highlight the interplay of exploration and socioemotional behaviors across development and suggest that societal norms may modulate their expression in naturalistic contexts.

Behavioral and Neural Signatures of Working Memory in Childhood.

Working memory function changes across development and varies across individuals. The patterns of behavior and brain function that track individual differences in working memory during human development, however, are not well understood. Here, we establish associations between working memory, other cognitive abilities, and functional MRI (fMRI) activation in data from over 11,500 9- to 10-year-old children (both sexes) enrolled in the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing longitudinal study in the United States. Behavioral analyses reveal robust relationships between working memory, short-term memory, language skills, and fluid intelligence. Analyses relating out-of-scanner working memory performance to memory-related fMRI activation in an emotional n-back task demonstrate that frontoparietal activity during a working memory challenge indexes working memory performance. This relationship is domain specific, such that fMRI activation related to emotion processing during the emotional n-back task, inhibitory control during a stop-signal task (SST), and reward processing during a monetary incentive delay (MID) task does not track memory abilities. Together, these results inform our understanding of individual differences in working memory in childhood and lay the groundwork for characterizing the ways in which they change across adolescence.SIGNIFICANCE STATEMENT Working memory is a foundational cognitive ability that changes over time and varies across individuals. Here, we analyze data from over 11,500 9- to 10-year-olds to establish relationships between working memory, other cognitive abilities, and frontoparietal brain activity during a working memory challenge, but not during other cognitive challenges. Our results lay the groundwork for assessing longitudinal changes in working memory and predicting later academic and other real-world outcomes.

Processing of Task-Irrelevant Race Information is Associated with Diminished Cognitive Control in Black and White Individuals.

The race of an individual is a salient physical feature that is rapidly processed by the brain and can bias our perceptions of others. How the race of others explicitly impacts our actions toward them during intergroup contexts is not well understood. In the current study, we examined how task-irrelevant race information influences cognitive control in a go/no-go task in a community sample of Black (n = 54) and White (n = 51) participants. We examined the neural correlates of behavioral effects using functional magnetic resonance imaging and explored the influence of implicit racial attitudes on brain-behavior associations. Both Black and White participants showed more cognitive control failures, as indexed by dprime, to Black versus White faces, despite the irrelevance of race to the task demands. This behavioral pattern was paralleled by greater activity to Black faces in the fusiform face area, implicated in processing face and in-group information, and lateral orbitofrontal cortex, associated with resolving stimulus-response conflict. Exploratory brain-behavior associations suggest different patterns in Black and White individuals. Black participants exhibited a negative association between fusiform activity and response time during impulsive errors to Black faces, whereas White participants showed a positive association between lateral OFC activity and cognitive control performance to Black faces when accounting for implicit racial associations. Together our findings propose that attention to race information is associated with diminished cognitive control that may be driven by different mechanisms for Black and White individuals.

Associative memory persistence in 3- to 5-year-olds.

Adults struggle to recollect episodic memories from early life. This phenomenon-referred to as "infantile" and "childhood amnesia"-has been widely observed across species and is characterized by rapid forgetting from birth until early childhood. While a number of studies have focused on infancy, few studies have examined the persistence of memory for newly learned associations during the putative period of childhood amnesia. In this study, we investigated forgetting in 137 children ages 3-5 years old by using an interactive storybook task. We assessed associative memory between subjects after 5-min, 24-h, and 1-week delay periods. Across all delays, we observed a significant increase in memory performance with age. While all ages demonstrated above-chance memory performance after 5-min and 24-h delays, we observed chance-level memory accuracy in 3-year-olds following a 1-week delay. The observed age differences in associative memory support the proposal that hippocampal-dependent memory systems undergo rapid development during the preschool years. These data have the potential to inform future work translating memory persistence and malleability research from rodent models to humans by establishing timescales at which we expect young children to forget newly learned associations.

Aversive learning strengthens episodic memory in both adolescents and adults.

Adolescence is often filled with positive and negative emotional experiences that may change how individuals remember and respond to stimuli in their environment. In adults, aversive events can both enhance memory for associated stimuli as well as generalize to enhance memory for unreinforced but conceptually related stimuli. The present study tested whether learned aversive associations similarly lead to better memory and generalization across a category of stimuli in adolescents. Participants completed an olfactory Pavlovian category conditioning task in which trial-unique exemplars from one of two categories were partially reinforced with an aversive odor. Participants then returned 24 h later to complete a recognition memory test. We found better corrected recognition memory for the reinforced versus the unreinforced category of stimuli in both adults and adolescents. Further analysis revealed that enhanced recognition memory was driven specifically by better memory for the reinforced exemplars. Autonomic arousal during learning was also related to subsequent memory. These findings build on previous work in adolescent and adult humans and rodents showing comparable acquisition of aversive Pavlovian conditioned responses across age groups and demonstrate that memory for stimuli with an acquired aversive association is enhanced in both adults and adolescents.

Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species.

Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.

Combined effects of peer presence, social cues, and rewards on cognitive control in adolescents.

Developmental scientists have examined the independent effects of peer presence, social cues, and rewards on adolescent decision-making and cognitive control. Yet, these contextual factors often co-occur in real world social situations. The current study examined the combined effects of all three factors on cognitive control, and its underlying neural circuitry, using a task to better capture adolescents' real world social interactions. A sample of 176 participants ages 13-25, was scanned while performing an adapted go/no-go task alone or in the presence of a virtual peer. The task included brief positive social cues and sustained periods of positive arousal. Adolescents showed diminished cognitive control to positive social cues when anticipating a reward in the presence of peers relative to when alone, a pattern not observed in older participants. This behavioral pattern was paralleled by enhanced orbitofrontal activation. The results demonstrate the synergistic impact of social and reward influences on cognitive control in adolescents.

The Impact of Emotional States on Cognitive Control Circuitry and Function.

Typically in the laboratory, cognitive and emotional processes are studied separately or as a stream of fleeting emotional stimuli embedded within a cognitive task. Yet in life, thoughts and actions often occur in more lasting emotional states of arousal. The current study examines the impact of emotions on actions using a novel behavioral paradigm and functional neuroimaging to assess cognitive control under sustained states of threat (anticipation of an aversive noise) and excitement (anticipation of winning money). Thirty-eight healthy adult participants were scanned while performing an emotional go/no-go task with positive (happy faces), negative (fearful faces), and neutral (calm faces) emotional cues, under threat or excitement. Cognitive control performance was enhanced during the excited state relative to a nonarousing control condition. This enhanced performance was paralleled by heightened activity of frontoparietal and frontostriatal circuitry. In contrast, under persistent threat, cognitive control was diminished when the valence of the emotional cue conflicted with the emotional state. Successful task performance in this conflicting emotional condition was associated with increased activity in the posterior cingulate cortex, a default mode network region implicated in complex processes such as processing emotions in the context of self and monitoring performance. This region showed positive coupling with frontoparietal circuitry implicated in cognitive control, providing support for a role of the posterior cingulate cortex in mobilizing cognitive resources to improve performance. These findings suggest that emotional states of arousal differentially modulate cognitive control and point to the potential utility of this paradigm for understanding effects of situational and pathological states of arousal on behavior.

When Is an Adolescent an Adult? Assessing Cognitive Control in Emotional and Nonemotional Contexts.

An individual is typically considered an adult at age 18, although the age of adulthood varies for different legal and social policies. A key question is how cognitive capacities relevant to these policies change with development. The current study used an emotional go/no-go paradigm and functional neuroimaging to assess cognitive control under sustained states of negative and positive arousal in a community sample of one hundred ten 13- to 25-year-olds from New York City and Los Angeles. The results showed diminished cognitive performance under brief and prolonged negative emotional arousal in 18- to 21-year-olds relative to adults over 21. This reduction in performance was paralleled by decreased activity in fronto-parietal circuitry, implicated in cognitive control, and increased sustained activity in the ventromedial prefrontal cortex, involved in emotional processes. The findings suggest a developmental shift in cognitive capacity in emotional situations that coincides with dynamic changes in prefrontal circuitry. These findings may inform age-related social policies.

Teens impulsively react rather than retreat from threat.

There is a significant inflection in risk taking and criminal behavior during adolescence, but the basis for this increase remains largely unknown. An increased sensitivity to rewards has been suggested to explain these behaviors, yet juvenile offences often occur in emotionally charged situations of negative valence. How behavior is altered by changes in negative emotional processes during adolescence has received less attention than changes in positive emotional processes. The current study uses a measure of impulsivity in combination with cues that signal threat or safety to assess developmental changes in emotional responses to threat cues. We show that adolescents, especially males, impulsively react to threat cues relative to neutral ones more than adults or children, even when instructed not to respond. This adolescent-specific behavioral pattern is paralleled by enhanced activity in limbic cortical regions implicated in the detection and assignment of emotional value to inputs and in the subsequent regulation of responses to them when successfully suppressing impulsive responses to threat cues. In contrast, prefrontal control regions implicated in detecting and resolving competing responses show an adolescent-emergent pattern (i.e. greater activity in adolescents and adults relative to children) during successful suppression of a response regardless of emotion. Our findings suggest that adolescence is a period of heightened sensitivity to social and emotional cues that results in diminished regulation of behavior in their presence.

The rational use of causal inference to guide reinforcement learning strengthens with age.

Beliefs about the controllability of positive or negative events in the environment can shape learning throughout the lifespan. Previous research has shown that adults' learning is modulated by beliefs about the causal structure of the environment such that they update their value estimates to a lesser extent when the outcomes can be attributed to hidden causes. This study examined whether external causes similarly influenced outcome attributions and learning across development. Ninety participants, ages 7 to 25 years, completed a reinforcement learning task in which they chose between two options with fixed reward probabilities. Choices were made in three distinct environments in which different hidden agents occasionally intervened to generate positive, negative, or random outcomes. Participants' beliefs about hidden-agent intervention aligned with the true probabilities of the positive, negative, or random outcome manipulation in each of the three environments. Computational modeling of the learning data revealed that while the choices made by both adults (ages 18-25) and adolescents (ages 13-17) were best fit by Bayesian reinforcement learning models that incorporate beliefs about hidden-agent intervention, those of children (ages 7-12) were best fit by a one learning rate model that updates value estimates based on choice outcomes alone. Together, these results suggest that while children demonstrate explicit awareness of the causal structure of the task environment, they do not implicitly use beliefs about the causal structure of the environment to guide reinforcement learning in the same manner as adolescents and adults.

Causal Information-Seeking Strategies Change Across Childhood and Adolescence.

Intervening on causal systems can illuminate their underlying structures. Past work has shown that, relative to adults, young children often make intervention decisions that appear to confirm a single hypothesis rather than those that optimally discriminate alternative hypotheses. Here, we investigated how the ability to make informative causal interventions changes across development. Ninety participants between the ages of 7 and 25 completed 40 different puzzles in which they had to intervene on various causal systems to determine their underlying structures. Each puzzle comprised a three- or four-node computer chip with hidden wires. On each trial, participants viewed two possible arrangements of the chip's hidden wires and had to select a single node to activate. After observing the outcome of their intervention, participants selected a wire configuration and rated their confidence in their selection. We characterized participant choices with a Bayesian measurement model that indexed the extent to which participants selected nodes that would best disambiguate the two possible causal structures versus those that had high causal centrality in one of the two causal hypotheses but did not necessarily discriminate between them. Our model estimates revealed that the use of a discriminatory strategy increased through early adolescence. Further, developmental improvements in intervention strategy were related to changes in the ability to accurately judge the strength of evidence that interventions revealed, as indexed by participants' confidence in their selections. Our results suggest that improvements in causal information-seeking extend into adolescence and may be driven by metacognitive sensitivity to the efficacy of previous interventions in discriminating competing ideas.

Development of the emotional brain.

In this article, we highlight the importance of dynamic reorganization of neural circuitry during adolescence, as it relates to the development of emotion reactivity and regulation. We offer a neurobiological account of hierarchical, circuit-based changes that coincide with emotional development during this time. Recent imaging studies suggest that the development of the emotional brain involves a cascade of changes in limbic and cognitive control circuitry. These changes are particularly pronounced during adolescence, when the demand for self regulation across a variety of emotional and social situations may be greatest. We propose that hierarchical changes in circuitry, from subcortico-subcortical to subcortico-cortical to cortico-subcortical and finally to cortico-cortical, may underlie the gradual changes in emotion reactivity and regulation throughout adolescence into young adulthood, with changes at each level being necessary for the instantiation of changes at the next level.

The racially diverse affective expression (RADIATE) face stimulus set.

Faces are often used in psychological and neuroimaging research to assess perceptual and emotional processes. Most available stimulus sets, however, represent minimal diversity in both race and ethnicity, which may confound understanding of these processes in diverse/racially heterogeneous samples. Having a diverse stimulus set of faces and emotional expressions could mitigate these biases and may also be useful in research that specifically examines the effects of race and ethnicity on perceptual, emotional and social processes. The racially diverse affective expression (RADIATE) face stimulus set is designed to provide an open-access set of 1,721 facial expressions of Black, White, Hispanic and Asian adult models. Moreover, the diversity of this stimulus set reflects census data showing a change in demographics in the United States from a white majority to a nonwhite majority by 2020. Psychometric results are provided describing the initial validity and reliability of the stimuli based on judgments of the emotional expressions.

The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites.

The ABCD study is recruiting and following the brain development and health of over 10,000 9-10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature.