Emotion regulation and reactivity are associated with cortical thickness in early to mid-childhood.

This study explored the neural correlates of emotion regulation and emotional reactivity in early to mid-childhood. A sample of 96 children (70% White, mid-to-high socioeconomic status) aged 3-8 years provided structural neuroimaging data and caregivers reported on emotion regulation and emotional reactivity. The amygdala, insula, inferior frontal gyrus, anterior cingulate cortex, and medial orbitofrontal cortex were explored as a priori regions of interest (ROIs). ROI analyses revealed that emotion regulation was positively associated with cortical thickness in the insula, whereas emotional reactivity was negatively associated with cortical thickness in the inferior frontal gyrus. Exploratory whole-brain analyses suggested positive associations between emotion regulation and both left superior temporal thickness and right inferior temporal thickness, as well as negative associations between emotional reactivity and left superior temporal thickness. There were no significant associations between emotional regulation or reactivity and amygdala volume or cortical surface area. These findings support the notion that surface area and cortical thickness are distinct measures of brain maturation. In sum, these findings suggest that children may rely on a wider set of neural regions for emotion regulation and reactivity than adults, which is consistent with theories of interactive specialization across the life span.

How Behavior Shapes the Brain and the Brain Shapes Behavior: Insights from Memory Development.

Source memory improves substantially during childhood. This improvement is thought to be closely related to hippocampal maturation. As previous studies have mainly used cross-sectional designs to assess relations between source memory and hippocampal function, it remains unknown whether changes in the brain precede improvements in memory or vice versa. To address this gap, the current study used an accelerated longitudinal design (n = 200, 100 males) to follow 4- and 6-year-old human children for 3 years. We traced developmental changes in source memory and intrinsic hippocampal functional connectivity and assessed differences between the 4- and 6-year-old cohorts in the predictive relations between source memory changes and intrinsic hippocampal functional connectivity in the absence of a demanding task. Consistent with previous studies, there were age-related increases in source memory and intrinsic functional connectivity between the hippocampus and cortical regions known to be involved during memory encoding. Novel findings showed that changes in memory ability early in life predicted later connectivity between the hippocampus and cortical regions and that intrinsic hippocampal functional connectivity predicted later changes in source memory. These findings suggest that behavioral experience and brain development are interactive, bidirectional processes, such that experience shapes future changes in the brain and the brain shapes future changes in behavior. Results also suggest that both timing and location matter, as the observed effects depended on both children's age and the specific brain ROIs. Together, these findings add critical insight into the interactive relations between cognitive processes and their underlying neurologic bases during development.SIGNIFICANCE STATEMENT Cross-sectional studies have shown that the ability to remember the contextual details of previous experiences (i.e., source memory) is related to hippocampal development in childhood. It is unknown whether hippocampal functional changes precede improvements in memory or vice versa. By using an accelerated longitudinal design, we found that early source memory changes predicted later intrinsic hippocampal functional connectivity and that this connectivity predicted later source memory changes. These findings suggest that behavioral experience and brain development are interactive, bidirectional processes, such that experience shapes future changes in the brain and the brain shapes future behavioral changes. Moreover, these interactions varied as a function of children's age and brain region, highlighting the importance of a developmental perspective when investigating brain-behavior interactions.

A meta-analysis of the relation between hippocampal volume and memory ability in typically developing children and adolescents.

Memory is supported by a network of brain regions, with the hippocampus serving a critical role in this cognitive process. Previous meta-analyses on the association between hippocampal structure and memory have largely focused on adults. Multiple studies have since suggested that hippocampal volume is related to memory performance in children and adolescents; however, the strength and direction of this relation varies across reports, and thus, remains unclear. To further understand this brain-behavior relation, we conducted a meta-analysis to investigate the association between hippocampal volume (assessed as total volume) and memory during typical development. Across 25 studies and 61 memory outcomes with 1357 participants, results showed a small, but significant, positive association between total hippocampal volume and memory performance. Estimates of the variability across studies in the relation between total volume and memory were not explained by differences in memory task type (delayed vs. immediate; relational vs. nonrelational), participant age range, or the method of normalization of hippocampal volumes. Overall, findings suggest that larger total hippocampal volume relates to better memory performance in children and adolescents and that this relation is similar across the memory types and age ranges assessed. To facilitate enhanced generalization across studies in the future, we discuss considerations for the field moving forward.

Parental hostility predicts reduced cortical thickness in males.

Although impacts of negative parenting on children's brain development are well-documented, little is known about how these associations may differ for males and females in childhood. We examined interactions between child sex and early and concurrent parental hostility on children's cortical thickness and surface area. Participants included 63 children (50.8% female) assessed during early childhood (Wave 1: M age = 4.23 years, SD = 0.84) and again three years later (Wave 2: M age = 7.19 years, SD = 0.89) using an observational parent-child interaction task. At Wave 2, children completed a structural MRI scan. Analyses focused on regions of interest. After correcting for multiple comparisons, Wave 1 parental hostility predicted males' reduced thickness in middle frontal and fusiform cortices, and Wave 2 parental hostility was concurrently associated with males' reduced thickness in the middle frontal cortex. Interactions between sex and parenting on children's surface area did not survive corrections for multiple comparisons. Our findings provide support for a male-specific neural vulnerability of hostile parenting across development. Results have important implications for uncovering neural pathways to sex-differences in psychopathology, learning, and cognitive disabilities.

Early childhood cumulative risk is associated with decreased global brain measures, cortical thickness, and cognitive functioning in school-age children.

Children exposed to multiple risk factors early in life are increasingly more likely to suffer from a host of cognitive impairments across development. However, little work has identified the neurobiological mechanisms linking early cumulative risk and cognitive functioning. The current study examined the impact of cumulative risk assessed during early childhood on neural and cognitive outcomes measured 3 years later when children were school-aged. Participants included 63 children assessed during preschool (age: M = 4.23 years, SD = 0.84) and 3 years later (age: M = 7.19 years, SD = 0.89). Early cumulative risk was defined by the presence of low family income, a single parent household, low parental education, child exposure to parental depression, child exposure to high parental hostility, and high levels of stressful life events. Children's exposure to stressors in the past year, cognitive abilities, and brain structure were assessed at follow-up. Early cumulative risk was prospectively associated with reduced total gray matter volume, cortex volume, right superior parietal and inferior parietal thickness, and poorer attention shifting and memory. Right superior parietal thickness mediated associations between early risk and recall memory. Results highlight neural variations associated with early cumulative risk and suggest potential neural pathways from early risk to later childhood cognitive impairments.

Longitudinal development of hippocampal subregions from early- to mid-childhood.

Early childhood is characterized by vast changes in behaviors supported by the hippocampus and an increased susceptibility of the hippocampus to environmental influences. Thus, it is an important time to investigate the development of the hippocampus. Existing research suggests subregions of the hippocampus (i.e., head, body, tail) have dissociable functions and that the relations between subregions and cognitive abilities vary across development. However, longitudinal research examining age-related changes in subregions in humans, particularly during early childhood (i.e., 4-6 years), is limited. Using a large sample of 184 healthy 4- to 8-year-old children, the present study is the first to characterize developmental changes in hippocampal subregion volume from early- to mid-childhood. Results reveal differential developmental trajectories in hippocampal head, body, and tail during this period. Specifically, head volume showed a quadratic pattern of change, and both body and tail showed linear increases, resulting in a pattern of cubic change for total hippocampal volume. Further, main effects of sex on hippocampal volume (males > females) and hemispheric differences in developmental trajectories were observed. These findings provide an improved understanding of the development of the hippocampus and have important implications for research investigating a range of cognitive abilities and behaviors.

The interactive effects of peers and alcohol on functional brain connectivity in young adults.

Alcohol and peer influence are known to have independent effects on risky decision making. We investigated combined influences of peers and alcohol on functional brain connectivity and behavior. Young adults underwent fMRI while completing response inhibition (Go/No-Go) and risky driving (Stoplight) tasks. Intoxicated participants made more mistakes on Go/No-Go, and showed diminished connectivity between the anterior insular cortex (AIC) and regions implicated in executive function (e.g., dorsal anterior cingulate). During the Stoplight game, peer observation was associated with increased connectivity between the AIC and regions implicated in social cognition (e.g., ventromedial prefrontal cortex). Alcohol and peers also exerted interactive influences, such that some connectivity changes only occurred when participants were observed by peers and under the influence of alcohol. These findings suggest that brain systems underlying decision making function differently under the combined influence of alcohol and peers, and highlight mechanisms through which this combination of factors is particularly risky for youth.

Protracted hippocampal development is associated with age-related improvements in memory during early childhood.

The hippocampus is a structure that is critical for memory. Previous studies have shown that age-related differences in specialization along the longitudinal axis of this structure (i.e., subregions) and within its internal circuitry (i.e., subfields) relate to age-related improvements in memory in school-age children and adults. However, the influence of age on hippocampal development and its relations with memory ability earlier in life remains under-investigated. This study examined effects of age and sex on hippocampal subregion (i.e., head, body, tail) and subfield (i.e., subiculum, CA1, CA2-4/DG) volumes, and their relations with memory, using a large sample of 4- to 8-year-old children. Results examining hippocampal subregions suggest influences of both age and sex on the hippocampal head during early childhood. Results examining subfields within hippocampal head suggest these age effects may arise from CA1, whereas sex differences may arise from subiculum and CA2-4/DG. Memory ability was not associated with hippocampal subregion volume but was associated with subfield volume. Specifically, within the hippocampal head, relations between memory and CA1 were moderated by age; in younger children bigger was better, whereas in older children smaller was superior. Within the hippocampal body, smaller CA1 and larger CA2-4/DG contributed to better memory performance across all ages. Together, these results shed light on hippocampal development during early childhood and support claims that the prolonged developmental trajectory of the hippocampus contributes to memory development early in life.

Peers influence adolescent reward processing, but not response inhibition.

Most adolescent risk taking occurs in the presence of peers. Prior research suggests that peers alter adolescents' decision making by increasing reward sensitivity and the engagement of regions involved in the processing of rewards, primarily the striatum. However, the potential influence of peers on the capacity for impulse control, and the associated recruitment of the brain's control circuitry, has not yet been adequately examined. In the current study, adolescents underwent functional neuroimaging while they completed interleaved rounds of risk-taking and response-inhibition tasks. Social context was manipulated such that the participants believed they were either playing alone and unobserved, or watched by an anonymous peer. Compared to those who completed the tasks alone, adolescents in the peer condition took more risks during the risk-taking task and exhibited relatively heightened activation of the striatum. Activity within this striatal region also predicted individual differences in overall risk taking. In contrast, the presence of peers had no effect on behavioral response inhibition and had minimal impact on the engagement of typical cognitive control regions. In a subregion of the anterior insula engaged mutually by both tasks, activity was again found to be sensitive to social context during the risk-taking task, but not during the response-inhibition task. These findings extend the evidence that the presence of peers biases adolescents towards risk taking by increasing reward sensitivity rather than disrupting cognitive control.

Adolescent risk-taking is predicted by individual differences in cognitive control over emotional, but not non-emotional, response conflict.

While much research on adolescent risk behaviour has focused on the development of prefrontal self-regulatory mechanisms, prior studies have elicited mixed evidence of a relationship between individual differences in the capacity for self-regulation and individual differences in risk taking. To explain these inconsistent findings, it has been suggested that the capacity for self-regulation may be, for most adolescents, adequately mature to produce adaptive behaviour in non-affective, "cold" circumstances, but that adolescents have a more difficult time exerting control in affective, "hot" contexts. To further explore this claim, the present study examined individual differences in self-control in the face of affective and non-affective response conflict, and examined whether differences in the functioning of cognitive control processes under these different conditions was related to risk taking. Participants completed a cognitive Stroop task, an emotional Stroop task, and a risky driving task known as the Stoplight game. Regression analyses showed that performance on the emotional Stroop task predicted laboratory risk-taking in the driving task, whereas performance on the cognitive Stroop task did not exhibit the same trend. This pattern of results is consistent with theories of adolescent risk-taking that emphasise the impacts of affective contextual influences on the ability to enact effective cognitive control.

EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort.

Objective: Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children's well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better. Methods: The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences. Results: The sample comprised 651 pediatric patients (339 females, M age = 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers' tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74). Conclusions: Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.

Longitudinal Exploration of Binding Ability across Early Childhood: The Differential Contribution of Hits and False Alarms.

Childhood is a period of pronounced improvements in children's ability to remember connections between details of an event (i.e. binding ability). However, the mechanisms supporting these changes remain unclear. Prior evidence is mixed, with some proposing that improvements in the ability to identify previous connections (i.e. increases in hits) account for memory changes, whereas other evidence suggests changes are additionally supported by the ability to identify inaccurate connections (i.e. decreases in false alarms). To disentangle the role of each process, we investigated changes in hits and false alarms within the same paradigm. The present study of 200 4-to-8-year-old children (100 female) used a cohort sequential design to assess longitudinal change in binding ability. Developmental trajectories of d', hit, and false alarm rates were examined using latent growth analysis. Findings demonstrated non-linear improvements in children's binding ability from age 4-to-8-years. Improvements were differentially supported by hits and false alarms. Hit rates improved non-linearly from 4-to-8-years, with greater growth from 4-to-6-years. False alarm rates did not significantly change from 4-to-6-years, but significantly decreased from 6-to-8-years. Overall, findings show improvements in binding ability are predominantly supported by increased hit rates between 4-to-6-years and by both increasing hit rates and decreasing false alarms rates between 6-to-8-years. Together, these results suggest that binding development is non-linear and that mechanisms underlying improvements differ across childhood.

Socioeconomic disadvantage and episodic memory ability in the ABCD sample: Contributions of hippocampal subregion and subfield volumes.

Socioeconomic disadvantage is associated with volumetric differences in stress-sensitive neural structures, including the hippocampus, and deficits in episodic memory. Rodent studies provide evidence that memory deficits arise via stress-related structural differences in hippocampal subdivisions; however, human studies have only provided limited evidence to support this notion. We used a sample of 10,695 9-13-year-old participants from two timepoints of the Adolescent Brain and Cognitive Development (ABCD) Study to assess whether socioeconomic disadvantage relates to episodic memory performance through hippocampal volumes. We explored associations among socioeconomic disadvantage, measured via the Area Deprivation Index (ADI), concurrent subregion (anterior, posterior) and subfield volumes (CA1, CA3, CA4/DG, subiculum), and episodic memory, assessed via the NIH Toolbox Picture Sequence Memory Test at baseline and 2-year follow-up (Time 2). Results showed that higher baseline ADI related to smaller concurrent anterior, CA1, CA4/DG, and subiculum volumes and poorer Time 2 memory performance controlling for baseline memory. Moreover, anterior, CA1, and subiculum volumes mediated the longitudinal association between the ADI and memory. Results suggest that greater socioeconomic disadvantage relates to smaller hippocampal subregion and subfield volumes and less age-related improvement in memory. These findings shed light on the neural mechanisms linking socioeconomic disadvantage and cognitive ability in childhood.

Hippocampal subregion volume in high-risk offspring is associated with increases in depressive symptoms across the transition to adolescence.

BACKGROUND: The hippocampus has been implicated in the pathophysiology of depression. This study examined whether youth hippocampal subregion volumes were differentially associated with maternal depression history and youth's depressive symptoms across the transition to adolescence. METHODS: 74 preadolescent offspring (Mage=10.74+/-0.84 years) of mothers with (n = 33) and without a lifetime depression history (n = 41) completed a structural brain scan. Youth depressive symptoms were assessed with clinical interviews and mother- and youth-reports prior to the neuroimaging assessment at age 9 (Mage=9.08+/-0.29 years), at the neuroimaging assessment, and in early adolescence (Mage=12.56+/-0.40 years). RESULTS: Maternal depression was associated with preadolescent offspring's reduced bilateral hippocampal head volumes and increased left hippocampal body volume. Reduced bilateral head volumes were associated with offspring's increased concurrent depressive symptoms. Furthermore, reduced right hippocampal head volume mediated associations between maternal depression and increases in offspring depressive symptoms from age 9 to age 12. LIMITATIONS: This study included a modest-sized sample that was oversampled for early temperamental characteristics, one neuroimaging assessment, and no correction for multiple comparisons. CONCLUSIONS: Findings implicate reductions in hippocampal head volume in the intergenerational transmission of risk from parents to offspring.

Empirical Evidence Supporting Neural Contributions to Episodic Memory Development in Early Childhood: Implications for Childhood Amnesia.

Memories for events that happen early in life are fragile-they are forgotten more quickly than expected based on typical adult rates of forgetting. Although numerous factors contribute to this phenomenon, data show one major source of change is the protracted development of neural structures related to memory. Recent empirical studies in early childhood reveal that the development of specific subdivisions of the hippocampus (i.e., the dentate gyrus) are related directly to variations in memory. Yet the hippocampus is only one region within a larger network supporting memory. Data from young children have also shown that activation of cortical regions during memory tasks and the functional connectivity between the hippocampus and cortex relate to memory during this period. Taken together, these results suggest that protracted neural development of the hippocampus, cortex, and connections between these regions contribute to the fragility of memories early in life and may ultimately contribute to childhood amnesia.

Early positive parenting and maternal depression history predict children's relational binding ability at school-age.

Research has indicated age-related improvements in relational binding, an important process of episodic memory, across development. However, little research has focused on individual differences in relational binding and factors contributing to this variation. Although differences may arise from various sources, early caregiving has been shown to impact aspects of memory related to relational binding and also the hippocampus, a structure critical to binding. The present study investigated the influences of early and concurrent parenting and maternal lifetime depression history on children's ability to successfully bind details and retain this information across a delay. A total of 97 children are included in this report. Children were part of a longitudinal study with testing at preschool age (Time 1: 3-5 years) and school age (Time 2: approximately 3 years later). At both time points, positive and negative parenting behaviors were assessed during observational parenting tasks and maternal depression history was assessed with a clinical interview. At Time 2, a composite binding score was derived from two episodic memory tasks: a source memory task and a feature binding task. Findings indicated that early positive parenting predicted higher binding scores later in childhood whereas maternal depression was associated with lower scores. These results were robust even after taking into account child age, general cognitive ability, race, and parental education. These findings highlight 2 factors related to the caregiving environment, parenting and maternal depression, that contribute to individual differences in children's relational binding ability and underscore the importance of early experience on episodic memory development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Lasting effects of stress physiology on the brain: Cortisol reactivity during preschool predicts hippocampal functional connectivity at school age.

Prolonged exposure to glucocorticoid stress hormones, such as cortisol in humans, has been associated with structural and functional changes in the hippocampus. The majority of research demonstrating these associations in humans has been conducted in adult, clinical, or severely maltreated populations, with little research investigating these effects in young or more typically developing populations. The present study sought to address this gap by investigating longitudinal associations between preschool (3-5 years) and concurrent (5-9 years) cortisol reactivity to a laboratory stressor and hippocampal functional connectivity during a passive viewing fMRI scan. Results showed that, after controlling for concurrent cortisol reactivity, greater total cortisol release in response to a stressor during preschool predicted increased anterior and posterior hippocampal connectivity with the precuneus and cingulate gyrus at school-age. These findings are consistent with literature from adult and non-human investigations and suggest lasting impacts of early stress physiology on the brain.

Empathic responding and hippocampal volume in young children.

Empathic responding-the capacity to understand, resonate with, and respond sensitively to others' emotional experiences-is a complex human faculty that calls upon multiple social, emotional, and cognitive capacities and their underlying neural systems. Emerging evidence in adults has suggested that the hippocampus and its associated network may play an important role in empathic responding, possibly via processes such as memory of emotional events, but the contribution of this structure in early childhood is unknown. We examined concurrent associations between empathic responding and hippocampal volume in a sample of 78 children (ages 4-8 years). Larger bilateral hippocampal volume (adjusted for intracranial volume) predicted greater observed empathic responses toward an experimenter in distress, but only for boys. The association was not driven by a specific subregion of the hippocampus (head, body, tail), nor did it vary with age. Empathic responding was not significantly related to amygdala volume, suggesting specificity of relations with the hippocampus. Results support the proposal that hippocampal structure contributes to individual differences in children's empathic responding, consistent with research in adults. Findings shed light on an understudied structure in the complex neural systems supporting empathic responding and raise new questions regarding sex differences in the neurodevelopment of empathy in early childhood. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

When less is more: Thinner fronto-parietal cortices are associated with better forward digit span performance during early childhood.

Although research shows that working memory improves during early childhood, it remains unclear how the fronto-parietal network of cortical regions, known to support this ability in adults, relates to changes in young children. Measures of cortical thickness may be useful in investigating this association as they reflect age-related differences in gray matter and have been proposed to support age-related improvements in other cognitive abilities, but have only sparingly been tested empirically in early childhood. The present study sought to investigate relations between cortical thickness and performance on a digit span task in 200 4- to 8-year-old children using both a priori defined regions of interest related to working memory (superior frontal cortex, middle frontal cortex, anterior cingulate cortex, superior parietal cortex) and whole brain analyses. Results indicated a significant association between cortical thickness in each a priori defined fronto-parietal region and performance on digit span, such that those with a thinner cortex recalled more items than those with a thicker cortex. Similar regions emerged from the whole brain analyses, as did several other regions not typically included in the fronto-parietal network. Results of a mediation analysis indicated that age-related differences in behavior were partially explained by variations in thickness of anterior cingulate cortex, suggesting a potentially important role for this structure during early childhood. Overall, these results suggest that in children as young as 4 years of age there are associations between working memory abilities and thickness in cortical areas known to support working memory in adults.

Working Memory Training in Adolescents Decreases Laboratory Risk Taking in the Presence of Peers.

Adolescence is a period of heightened risk-taking relative to both adulthood and childhood, due in part to peers' increased influence on adolescent decision making. Because adolescents' choices have harmful consequences, there is great interest in specific interventions that might attenuate risk taking. We hypothesized that it might be possible to reduce adolescent risk taking through an intervention targeting the ability/tendency to engage cognitive control processes. While some studies of Working Memory Training (WMT) have indicated subsequent enhancement of adults' cognitive control abilities, potential impacts on adolescent cognitive control have not been explored. Accordingly, we tested whether four weeks of WMT (relative to Active Control Training, ACT) might increase performance on cognitive control measures and decrease risk-taking in adolescents. Adolescents receiving WMT, compared to those receiving ACT, exhibited some evidence of improved short-term memory performance following the 4-week training period. Improvements did not significantly transfer to performance on basic cognitive control measures. However, on two risk-taking tasks administered at post-training either with or without an anonymous peer audience, adolescents who received WMT evinced suppressed levels of risk taking when observed by peers, an effect not seen in ACT. Further work is needed to more fully characterize the potential of WMT interventions in stemming risk behavior within adolescent samples.