Early emotional caregiving environment and associations with memory performance and hippocampal volume in adolescents with prenatal drug exposure.

Early adversities, including prenatal drug exposure (PDE) and a negative postnatal emotional caregiving environment, impact children's long-term development. The protracted developmental course of memory and its underlying neural systems offer a valuable framework for understanding the longitudinal associations of pre- and postnatal factors on children with PDE. This study longitudinally examines memory and hippocampal development in 69 parent-child dyads to investigate how the early caregiving emotional environment affects children with PDE's neural and cognitive systems. Measures of physical health, drug exposure, caregiver stress, depression, and distress were collected between 0 and 24 months At age 14 years, adolescents completed multiple measures of episodic memory, and at ages 14 and 18 years, adolescents underwent magnetic resonance imaging (MRI) scans. Latent constructs of episodic memory and the caregiving environment were created using Confirmatory Factor Analysis. Multiple regressions revealed a negative emotional caregiving environment during infancy was associated with poor memory performance and smaller left hippocampal volumes at 14 years. Better memory performance at 14 years predicted larger right hippocampal volume at 18 years. At 18 years, the association between the emotional caregiving environment and hippocampal volume was moderated by sex, such that a negative emotional caregiving environment was associated with larger left hippocampal volumes in males but not females. Findings suggest that the postnatal caregiving environment may modulate the effects of PDE across development, influencing neurocognitive development.

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.

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.

Irritability in early to middle childhood: Cross-sectional and longitudinal associations with resting state amygdala and ventral striatum connectivity.

BACKGROUND: Irritability is a common symptom that may affect children's brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4-8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time. METHODS: Typically developing children, ages 4-8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a "younger" cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an "older" cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions. RESULTS: Cross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort. CONCLUSIONS: Findings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.

Influence of naps on sedentary time and physical activity in early childhood.

The objective was to determine if, in preschool-aged children, (1) nap habituality is associated with sedentary time and physical activity (movement behaviors), (2) nap physiology is associated with movement behaviors, and (3) if missing a nap, compared to taking a nap, affects movement behaviors on the same day and subsequent day. A within-subjects (44 children; 4.2 ± 0.6 years; 55.6% female), at-home study examined two experimental conditions (one afternoon each of nap- and wake-promotion with order counterbalanced) one week apart. Movement behaviors were derived from wrist-worn actigraphy (12.1 ± 3.1 days). Average movement behaviors were calculated from the overall study period with experimental days excluded. Movement behaviors were also extracted for the same day and the subsequent day of the two experimental conditions. Polysomnography was recorded during the nap-promoted condition. Children were classified as non-, intermediate-, or habitual-nappers. Although average movement behaviors were different between nap habituality groups, differences were not significant. There were no associations between movement behaviors and nap sleep stages, and no effects for nap condition or condition by nap habituality on same or next day movement behaviors. Findings do not suggest that naps and movement behaviors are related in children. Although a single missed nap was not detrimental to same or next day movement behaviors, future studies should explore effects of multiple days of subsequent nap restriction to examine potential cumulative effects.

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.

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.

Mothers' Attachment Representations and Children's Brain Structure.

Ample research demonstrates that parents' experience-based mental representations of attachment-cognitive models of close relationships-relate to their children's social-emotional development. However, no research to date has examined how parents' attachment representations relate to another crucial domain of children's development: brain development. The present study is the first to integrate the separate literatures on attachment and developmental social cognitive neuroscience to examine the link between mothers' attachment representations and 3- to 8-year-old children's brain structure. We hypothesized that mothers' attachment representations would relate to individual differences in children's brain structures involved in stress regulation-specifically, amygdala and hippocampal volumes-in part via mothers' responses to children's distress. We assessed 52 mothers' attachment representations (secure base script knowledge on the Attachment Script Assessment and self-reported attachment avoidance and anxiety on the Experiences in Close Relationships scale) and children's brain structure. Mothers' secure base script knowledge was significantly related to children's smaller left amygdala volume but was unrelated to hippocampal volume; we found no indirect links via maternal responses to children's distress. Exploratory analyses showed associations between mothers' attachment representations and white matter and thalamus volumes. Together, these preliminary results suggest that mothers' attachment representations may be linked to the development of children's neural circuitry related to stress regulation.

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.

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.

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.

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.

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.

Sleep and human cognitive development.

Emerging studies across learning domains have shed light on mechanisms underlying sleep's benefits during numerous developmental periods. In this conceptual review, we survey recent studies of sleep and cognition across infancy, childhood, and adolescence. By summarizing recent findings and integrating across studies with disparate approaches, we provide a novel understanding of sleep's role in human cognitive function. Collectively, these studies point to an interrelation between brain development, sleep, and cognition. Moreover, we point to gaps in our understanding, which inform the agenda for future research in developmental and sleep science.

Modeling longitudinal changes in hippocampal subfields and relations with memory from early- to mid-childhood.

The hippocampus has been suggested to show protracted postnatal developmental growth across childhood. Most previous studies during this developmental period have been cross-sectional in nature and have focused on age-related differences in either hippocampal subregions or subfields, but not both, potentially missing localized changes. This study capitalized on a latent structural equation modeling approach to examine the longitudinal development of hippocampal subfields (cornu ammonis (CA) 2-4/dentate gyrus (DG), CA1, subiculum) in both the head and the body of the hippocampus, separately, in 165 typically developing 4- to 8-year-old children. Our findings document differential development of subfields within hippocampal head and body. Specifically, within hippocampal head, CA1 volume increased between 4-5 years and within hippocampal body, CA2-4/DG and subiculum volume increased between 5-6 years. Additionally, changes in CA1 volume in the head and changes in subiculum in the body between 4-5 years related to improvements in memory between 4-5 years. These findings demonstrate the protracted development of subfields in vivo during early- to mid-childhood, illustrate the importance of considering subfields separately in the head and body of the hippocampus, document co-occurring development of brain and behavior, and highlight the strength of longitudinal data and latent modeling when examining brain development.

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.

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.

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.

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.

Prefrontal cortical thickness mediates the association between cortisol reactivity and executive function in childhood.

The impact of stress hormones, such as cortisol, on the brain is proposed to contribute to differences in executive function of school-age children from impoverished backgrounds. However, the association between cortisol reactivity, prefrontal cortex, and executive function is relatively unexplored in young children. The current longitudinal study examined whether 63 children's early preschool-age (3-5 years, Time 1) and concurrent school-age (5-9 years, Time 2) salivary cortisol reactivity were associated with executive function and prefrontal cortical thickness at school-age. Two measures of cortisol reactivity were calculated: area under the curve with respect to ground (AUCg; total cortisol release) and with respect to increase (AUCi; total change in cortisol). Results demonstrated that Time 2 total cortisol release was negatively associated with executive function, Time 1 total cortisol release positively related to right middle frontal cortical thickness, and Time 2 total cortisol change was negatively associated with right inferior frontal cortical thickness. Moreover, greater right middle frontal cortical thickness mediated the association between greater Time 1 total cortisol release and lower executive function. This study provides support for an early adversity framework in which individual differences in executive function in childhood are directly related to the variations of cortisol-release and the effects on the prefrontal cortex thickness.