Contributions of memory and brain development to the bioregulation of naps and nap transitions in early childhood.

The transition from multiple sleep bouts each day to a single overnight sleep bout (i.e., nap transition) is a universal process in human development. Naps are important during infancy and early childhood as they enhance learning through memory consolidation. However, a normal part of development is the transition out of naps. Understanding nap transitions is essential in order to maximize early learning and promote positive long-term cognitive outcomes. Here, we propose a novel hypothesis regarding the cognitive, physiological, and neural changes that accompany nap transitions. Specifically, we posit that maturation of the hippocampal-dependent memory network results in more efficient memory storage, which reduces the buildup of homeostatic sleep pressure across the cortex (as reflected by slow-wave activity), and eventually, contributes to nap transitions. This hypothesis synthesizes evidence of bioregulatory mechanisms underlying nap transitions and sheds new light on an important window of change in development. This framework can be used to evaluate multiple untested predictions from the field of sleep science and ultimately, yield science-based guidelines and policies regarding napping in childcare and early education settings.

The fornix supports episodic memory during childhood.

Episodic memory relies on the coordination of widespread brain regions that reconstruct spatiotemporal details of an episode. These topologically dispersed brain regions can rapidly communicate through structural pathways. Research in animal and human lesion studies implicate the fornix-the major output pathway of the hippocampus-in supporting various aspects of episodic memory. Because episodic memory undergoes marked changes in early childhood, we tested the link between the fornix and episodic memory in an age window of robust memory development (ages 4-8 years). Children were tested on the stories subtest from the Children's Memory Scale, a temporal order memory task, and a source memory task. Fornix streamlines were reconstructed using probabilistic tractography to estimate fornix microstructure. In addition, we measured fornix macrostructure and computed free water. To assess selectivity of our findings, we also reconstructed the uncinate fasciculus. Findings show that children's memory increases from ages 4 to 8 and that fornix micro- and macrostructure increases between ages 4 and 8. Children's memory performance across nearly every memory task correlated with individual differences in fornix, but not uncinate fasciculus, white matter. These findings suggest that the fornix plays an important role in supporting the development of episodic memory, and potentially semantic memory, in early childhood.

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.

Interactions between the hippocampus and fronto-parietal regions during memory encoding in early childhood.

The neural mechanisms underlying memory encoding have received much attention in the literature. Research in adults and school-age children suggest that the hippocampus and cortical regions in both frontal and parietal areas are involved in successful formation of memories. Overall, the hippocampus has been shown to interact with fronto-parietal regions to collaboratively support successful memory encoding for both individual items as well as item details (such as the source or color in which the item was originally encountered). To date, only one study has investigated neural regions engaged during memory encoding in children younger than 8 years of age, which is unfortunate since early childhood is a period of dramatic improvement in memory. This previous study indicated that both the hippocampus and cortical regions are involved during the encoding of subsequently remembered item details (i.e., sources). However, this study reported few interactions between these regions, and it did not explore item memory at a more general level. To fill these gaps, this article reanalyzed data from the previous report, aiming to examine the neural correlates of item memory during encoding in early childhood (4-8 years) and interactions between the hippocampus and fronto-parietal regions during encoding. Consistent with research in older individuals, both the hippocampus and fronto-parietal regions were found to participate in item memory encoding. Additionally, functional connectivity between hippocampus and fronto-parietal regions was significantly related to both subsequent item memory and subsequent source memory. Taken together, these findings suggest that not only the activation of individual brain regions (hippocampus and fronto-parietal regions) but also the functional connections between these regions are important for memory encoding. These data add to the growing literature providing insight into how the hippocampus and cortical regions interact to support memory during development.

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.

Developmental changes in episodic memory across early- to mid-childhood: insights from a latent longitudinal approach.

Episodic memory is a cornerstone ability that allows one to recall past events and the spatiotemporal context in which they occur. In an effort to characterise the development of this critical ability, many different tasks have been used independently to assess age-related variations in episodic memory. However, performance on memory tasks is multiply determined, and the extent to which different tasks with varying features relate to each other and represent episodic memory as a latent cognitive construct across childhood is unclear. The present study sought to address this question by exploring the feasibility of using four different laboratory-based tasks to characterise changes in episodic memory ability during early- to mid-childhood in 200 typically developing children (4-8 years). Using longitudinal data and a structural equation modeling framework, results suggest that multiple tests of episodic memory can be utilised to indicate a comparable latent construct of episodic memory ability over this period of development, and that this ability improves consistently between 4 to 8 years. Overall, results highlight that episodic memory measured as a construct increases at a similar rate over early- to mid-childhood and demonstrate the benefits of using multiple laboratory tasks to characterise developmental changes in episodic memory.

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.

Adapting event-related potential research paradigms for children: Considerations from research on the development of recognition memory.

Most developmental event-related potential (ERP) research uses experimental paradigms modified from research with adults. One major challenge is identifying how to adapt these paradigms effectively for use with younger individuals. This paper provides guidance for developmental adaptations by considering research on the development of recognition memory. We provide a brief overview of recognition memory tasks and ERP components associated with recognition memory in children and adults. Then, we provide some general recommendations, discuss common differences between ERP studies of recognition memory in adults and children (e.g., the type of stimuli presented, response modalities), and provide suggestions for assessing the effect of task modifications on ERP components of interest. Specifically, we recommend (a) testing both children and adults on the modified paradigm to allow for a continuity of findings across development, (b) comparing children of different ages on the modified paradigm based on expectations regarding when developmental change occurs for the cognitive process of interest, and (c) empirically assessing the effect of methodological differences between paradigms. To illustrate the latter, we analyzed data from our lab comparing memory-related ERP components when children experienced a 1-day, 2-day, or 1-week delay between encoding and retrieval.

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.

It's All in the Details: Relations Between Young Children's Developing Pattern Separation Abilities and Hippocampal Subfield Volumes.

The ability to keep similar experiences separate in memory is critical for forming unique and lasting memories, as many events share overlapping features (e.g., birthday parties, holidays). Research on memory in young children suggests their memories often lack high-resolution details, i.e., show impoverished pattern separation (PS). Recently developed assessments of PS suitable for children allow us to relate the formation of distinct, detailed memories for the development of the hippocampus, a neural structure critical for this ability in adults. The hippocampus displays a protracted developmental profile and underlies the ability to form detailed memories. This study examined age-related differences in hippocampal subfield volumes in 4- to 8-year-old children and relations with performance on a mnemonic similarity task (MST) designed to index memory specificity. Results revealed age-moderated associations between MST performance and cornu ammonis 2-4/dentate gyrus subfields. Specifically, age-related differences in the ability to form detailed memories tracked with normative patterns of volume increases followed by reductions over this age range. That is, greater volume correlated with better performance in younger children, whereas smaller volume correlated with better performance in older children. These findings support the hypothesis that developmental differences in hippocampal circuitry contribute to age-related improvements in detailed memory formation during this period.

Learning From Others: The Effects of Agency on Event Memory in Young Children.

Little is known about the influence of social context on children's event memory. Across four studies, we examined whether learning that could occur in the absence of a person was more robust when a person was present. Three-year-old children (N = 125) viewed sequential events that either included or excluded an acting agent. In Experiment 1, children who viewed an agent recalled more than children who did not. Experiments 2a and 2b utilized an eye tracker to demonstrate this effect was not due to differences in attention. Experiment 3 used a combined behavioral and event-related potential paradigm to show that condition effects were present in memory-related components. These converging results indicate a particular role for social knowledge in supporting memory for events.

Age- and performance-related differences in source memory retrieval during early childhood: Insights from event-related potentials.

Across early childhood, children's ability to remember individual items and the details that accompany these items (i.e., episodic memory) improves greatly. Given that these behavioral improvements coincide with increases in age, effects of age and performance are often confounded. This study used event-related potentials (ERPs) to investigate age- and performance-related differences in the neural processes underlying the development of memory for details during early childhood. Using a source memory paradigm, ERP components related to episodic memory, the negative component (Nc), and late slow wave (LSW) were examined in 4- to 8-year-old children. Analyses focused on trials for which children correctly remembered the source related to an item versus trials where the item was remembered but the source was forgotten. Results revealed LSW, but not Nc, differed as a function of age and performance. Specifically, LSW effects were similar across source correct and source incorrect trials in all high-performing children and in low-performing older children; however, LSW effects differed across conditions in low-performing younger children. Results show developmental differences in retrieval processes across early childhood and highlight the importance of considering age and performance when examining electrophysiological correlates of episodic memory during development.

The influence of age and performance on hippocampal function and the encoding of contextual information in early childhood.

Studies in school-aged children and adults consistently implicate hippocampus, cortical regions, and their interaction as being critical for memory. However, few studies have examined this neural network in younger children (<8 years), despite the fact that behavioral studies consistently report substantial improvements in memory earlier in life. This study aimed to fill this gap by integrating task-based (i.e., memory encoding task) and task-free fMRI scans in 4- to 8-year-old children. Results showed that during memory encoding the hippocampus and several cortical regions (e.g., inferior frontal gyrus, IFG) were activated, consistent with findings in older individuals. Novel findings during memory encoding showed: 1) additional regions (i.e., orbital frontal gyrus, OFG) were recruited, 2) hippocampal activation varied due to age and performance, and 3) differentiation of connectivity between hippocampal subregions and IFG was greater in older versus younger participants, implying increased speicalization with age. Novel findings from task-free fMRI data suggested the extent of functional differentiation along the longitudinal axis of the hippocampus, particularly between hippocampus and OFG, was moderated by both age and performance. Our findings support and extend previous research, suggesting that maturation of hippocampal activity, connectivity, and differentiation may all contribute to development of memory during early childhood.

Neural correlates of developing theory of mind competence in early childhood.

Theory of mind (ToM) encompasses a range of abilities that show different developmental time courses. However, relatively little work has examined the neural correlates of ToM during early childhood. In this study, we investigated the neural correlates of ToM in typically developing children aged 4-8 years using resting-state functional magnetic resonance imaging. We calculated whole-brain functional connectivity with the right temporo-parietal junction (RTPJ), a core region involved in ToM, and examined its relation to children's early, basic, and advanced components of ToM competence assessed by a parent-report measure. Total ToM and both basic and advanced ToM components, but not early, consistently showed a positive correlation with connectivity between RTPJ and posterior cingulate cortex/precuneus; advanced ToM was also correlated with RTPJ to left TPJ connectivity. However, early and advanced ToM components showed negative correlation with the right inferior/superior parietal lobe, suggesting that RTPJ network differentiation is also related to ToM abilities. We confirmed and extended these results using a Bayesian modeling approach demonstrating significant relations between multiple nodes of the mentalizing network and ToM abilities, with no evidence for differences in relations between ToM components. Our data provide new insights into the neural correlates of multiple aspects of ToM in early childhood and may have implications for both typical and atypical development of ToM.

Early parenting predicts hippocampal subregion volume via stress reactivity in childhood.

Rodent models indicate that parenting shapes offspring outcomes by programming the hypothalamic-pituitary-adrenal axis response to stress and, ultimately, altering brain structure and function. The present study tested this hypothesis and explored possible timing-dependent associations in a longitudinal sample of children (N = 63). At Time 1 (M = 4.23 ± 0.84 years) and Time 2 (M = 7.20 ± 0.89 years), children completed parent-child interaction tasks and a laboratory stressor after which salivary cortisol samples were collected. At Time 2, children also completed a structural MRI. Analyses revealed timing- and region-dependent associations between early and concurrent parenting and cortisol reactivity and hippocampal subregion volumes. Moreover, greater negative parenting during early childhood predicted greater cortisol reactivity three years later, which, in turn, led to reduced left hippocampal tail volume. Findings suggest that the hippocampus is sensitive to environmental influences during early childhood, a result that parallels findings from rodent models.

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.

Age-related differences in subjective recollection: ERP studies of encoding and retrieval.

The ability to mentally re-experience past events improves significantly from childhood to young adulthood; however, the mechanisms underlying this ability remain poorly understood, partially because different tasks are used across the lifespan. This study was designed to address this gap by assessing the development of event-related potential (ERP) correlates associated with subjective indices of recollection. Children, adolescents, and adults performed Tulving's () remember/know paradigm while ERPs were recorded during memory encoding (Experiment 1) and retrieval (Experiment 2). Behaviorally, children recognized fewer items than adolescents and adults. All age groups reliably made subjective judgments of recollection, although the ability to make these judgments improved with age. At encoding, the ERP effect associated with recollection was present and comparable across age groups. In contrast, the ERP effect associated with recollection at retrieval differed as a function of age group; specifically, this effect was absent in children, topographically widespread in adolescents, and, consistent with previous literature, maximal over left centro-parietal leads in adults. These findings suggest that encoding processes associated with the subsequent subjective experience of recollection may be similar among children, adolescents, and adults and that age-related improvement in recollection may be primarily attributable to the development of processes that follow the initial encoding of stimuli (i.e., consolidation, storage, retrieval).

Increasing relational memory in childhood with unitization strategies.

Young children often experience relational memory failures, which are thought to result from immaturity of the recollection processes presumed to be required for these tasks. However, research in adults has suggested that relational memory tasks can be accomplished using familiarity, a process thought to be mature by the end of early childhood. The goal of the present study was to determine whether relational memory performance could be improved in childhood by teaching young children memory strategies that have been shown to increase the contribution of familiarity in adults (i.e., unitization). Groups of 6- and 8-year-old children were taught to use visualization strategies that either unitized or did not unitize pictures and colored borders. Estimates of familiarity and recollection were extracted by fitting receiver operator characteristic curves (Yonelinas, Journal of Experimental Psychology: Learning, Memory, and Cognition 20, 1341-1354, 1994, Yonelinas, Memory & Cognition 25, 747-763, 1997) based on dual-process models of recognition. Bayesian analysis revealed that strategies involving unitization improved memory performance and increased the contribution of familiarity in both age groups.