A sensorimotor-association axis of thalamocortical connection development.

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence1-6. The brain's capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity7-12, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; total N = 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortex's sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.

Sensitivity to psychosocial influences at age 3 predicts mental health in middle childhood.

Children vary in how sensitive they are to experiences, with consequences for their developmental outcomes. In the current study, we investigated how behavioral sensitivity at age 3 years predicts mental health in middle childhood. Using a novel repeated measures design, we calculated child sensitivity to multiple psychological and social influences: parent praise, parent stress, child mood, and child sleep. We conceptualized sensitivity as the strength and direction of the relationship between psychosocial influences and child behavior, operationalized as toothbrushing time, at age 3 years. When children were 5-7 years old (n = 60), parents reported on children's internalizing and externalizing problems. Children who were more sensitive to their parents' praise at age 3 had fewer internalizing (r = -0.37, p = 0.016, pFDR = 0.042) and externalizing (r = -0.35, p = 0.021, pFDR = 0.042) problems in middle childhood. Higher average parent praise also marginally predicted fewer externalizing problems (r = -0.33, p = 0.006, pFDR = 0.057). Child sensitivity to mood predicted fewer internalizing (r = -0.32, p = 0.013, pFDR = 0.042) and externalizing (r = -0.38, p = 0.003, pFDR = 0.026) problems. By capturing variability in how children respond to daily fluctuations in their environment, we can contribute to the early prediction of mental health problems and improve access to early intervention services for children and families who need them most. RESEARCH HIGHLIGHTS: Children differ in how strongly their behavior depends on psychosocial factors including parent praise, child mood, child sleep, and parent stress. Children who are more sensitive to their parents' praise at age 3 have fewer internalizing and externalizing problems at age 5-7 years. Child sensitivity to mood also predicts fewer internalizing and externalizing problems.

A general exposome factor explains individual differences in functional brain network topography and cognition in youth.

Childhood environments are critical in shaping cognitive neurodevelopment. With the increasing availability of large-scale neuroimaging datasets with deep phenotyping of childhood environments, we can now build upon prior studies that have considered relationships between one or a handful of environmental and neuroimaging features at a time. Here, we characterize the combined effects of hundreds of inter-connected and co-occurring features of a child's environment ("exposome") and investigate associations with each child's unique, multidimensional pattern of functional brain network organization ("functional topography") and cognition. We apply data-driven computational models to measure the exposome and define personalized functional brain networks in pre-registered analyses. Across matched discovery (n=5139, 48.5% female) and replication (n=5137, 47.1% female) samples from the Adolescent Brain Cognitive Development study, the exposome was associated with current (ages 9-10) and future (ages 11-12) cognition. Changes in the exposome were also associated with changes in cognition after accounting for baseline scores. Cross-validated ridge regressions revealed that the exposome is reflected in functional topography and can predict performance across cognitive domains. Importantly, a single measure capturing a child's exposome could more accurately and parsimoniously predict cognition than a wealth of personalized neuroimaging data, highlighting the importance of children's complex, multidimensional environments in cognitive neurodevelopment.

Multilayer network associations between the exposome and childhood brain development.

Growing up in a high poverty neighborhood is associated with elevated risk for academic challenges and health problems. Here, we take a data-driven approach to exploring how measures of children's environments relate to the development of their brain structure and function in a community sample of children between the ages of 4 and 10 years. We constructed exposomes including measures of family socioeconomic status, children's exposure to adversity, and geocoded measures of neighborhood socioeconomic status, crime, and environmental toxins. We connected the exposome to two structural measures (cortical thickness and surface area, n = 170) and two functional measures (participation coefficient and clustering coefficient, n = 130). We found dense connections within exposome and brain layers and sparse connections between exposome and brain layers. Lower family income was associated with thinner visual cortex, consistent with the theory that accelerated development is detectable in early-developing regions. Greater neighborhood incidence of high blood lead levels was associated with greater segregation of the default mode network, consistent with evidence that toxins are deposited into the brain along the midline. Our study demonstrates the utility of multilayer network analysis to bridge environmental and neural explanatory levels to better understand the complexity of child development.

Developmental Correlates of Accelerated Molar Eruption in Early Childhood.

Background: Adversity has been linked to accelerated maturation. Molar eruption is a simple and scalable way to identify early maturation, but its developmental correlates remain unexplored. Thus, we examined whether accelerated maturation as indexed by molar eruption is associated with children's mental health or cognitive skills. Methods: Molar eruption was evaluated from T2-weighted magnetic resonance imaging in 117 children (63 female; ages 4-7 years). Parents reported on child mental health with the Child Behavior Checklist. Children completed standardized assessments of fluid reasoning, working memory, processing speed, crystallized knowledge, and math performance. Relationships between molar eruption and developmental outcomes were examined using linear models, with age, gender, and stress risk as covariates. Results: Earlier molar eruption was positively associated with children's externalizing symptoms (false discovery rate-corrected p [pFDR] = .027) but not internalizing symptoms, and the relationship with externalizing symptoms did not hold when controlling for stress risk. Earlier molar eruption was negatively associated with fluid reasoning (pFDR < .001), working memory (pFDR = .033), and crystallized knowledge (pFDR = .001). The association between molar eruption and both reasoning and crystallized knowledge held when controlling for stress risk. Molar eruption also partially mediated associations between stress risk and both reasoning (proportion mediated = 0.273, p = .004) and crystallized knowledge (proportion mediated = 0.126, p = .016). Conclusions: Accelerated maturation, as reflected in early molar eruption, may have consequences for cognitive development, perhaps because it constrains brain plasticity. Knowing the pace of a child's maturation may provide insight into the impact of a child's stress history on their cognitive development.

A systematic review of interventions to ameliorate the impact of adversity on brain development.

Adversity, including abuse, neglect, and poverty, impacts child brain development. However, the developing brain is highly plastic, and some of the impacts of childhood adversity may be mitigated by psychosocial interventions. The purpose of this review is to synthesize literature on neural outcomes of childhood interventions among individuals exposed to adversity. A systematic literature search identified 36 reports of 13 interventions. Overall, these studies provide evidence for experience-dependent plasticity in the developing brain. We synthesize studies in light of three themes. First, there was mixed evidence for a benefit of a younger age at intervention. Second, interventions tended to accelerate functional brain development, but the impact of interventions on the pace of structural brain development was less clear. Third, individual differences in intervention response were difficult to predict, in part due to small samples. However, there was significant variability in intervention type and timing, neuroimaging outcomes, and follow-up timing. Together, the studies reviewed here hold promise for the role of psychosocial interventions in ameliorating the neurodevelopmental consequences of childhood adversity.

Individual differences in T1w/T2w ratio development during childhood.

Myelination is a key developmental process that promotes rapid and efficient information transfer. Myelin also stabilizes existing brain networks and thus may constrain neuroplasticity, defined here as the brain's potential to change in response to experiences rather than the canonical definition as the process of change. Characterizing individual differences in neuroplasticity may shed light on mechanisms by which early experiences shape learning, brain and body development, and response to interventions. The T1-weighted/T2-weighted (T1w/T2w) MRI signal ratio is a proxy measure of cortical microstructure and thus neuroplasticity. Here, in pre-registered analyses, we investigated individual differences in T1w/T2w ratios in children (ages 4-10, n = 157). T1w/T2w ratios were positively associated with age within early-developing sensorimotor and attention regions. We also tested whether socioeconomic status, cognition (crystallized knowledge or fluid reasoning), and biological age (as measured with molar eruption) were related to T1w/T2w signal but found no significant effects. Associations among T1w/T2w ratios, early experiences, and cognition may emerge later in adolescence and may not be strong enough to detect in moderate sample sizes.

Intrinsic activity development unfolds along a sensorimotor-association cortical axis in youth.

Animal studies of neurodevelopment have shown that recordings of intrinsic cortical activity evolve from synchronized and high amplitude to sparse and low amplitude as plasticity declines and the cortex matures. Leveraging resting-state functional MRI (fMRI) data from 1,033 youths (ages 8-23 years), we find that this stereotyped refinement of intrinsic activity occurs during human development and provides evidence for a cortical gradient of neurodevelopmental change. Declines in the amplitude of intrinsic fMRI activity were initiated heterochronously across regions and were coupled to the maturation of intracortical myelin, a developmental plasticity regulator. Spatiotemporal variability in regional developmental trajectories was organized along a hierarchical, sensorimotor-association cortical axis from ages 8 to 18. The sensorimotor-association axis furthermore captured variation in associations between youths' neighborhood environments and intrinsic fMRI activity; associations suggest that the effects of environmental disadvantage on the maturing brain diverge most across this axis during midadolescence. These results uncover a hierarchical neurodevelopmental axis and offer insight into the progression of cortical plasticity in humans.

Associations between neighborhood socioeconomic status, parental education, and executive system activation in youth.

Socioeconomic status (SES) can impact cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may influence cognitive outcomes. Here, we sought to examine how SES at the neighborhood and family level impacts task-related activation of the executive system during adolescence and determine whether this effect mediates the relationship between SES and WM performance. To address these questions, we studied 1,150 youths (age 8-23) that completed a fractal n-back WM task during functional magnetic resonance imaging at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that both higher neighborhood SES and parental education were associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. The association of neighborhood SES remained significant when controlling for task performance, or related factors like exposure to traumatic events. Furthermore, high-dimensional multivariate mediation analysis identified distinct patterns of brain activity within the executive system that significantly mediated the relationship between measures of SES and task performance. These findings underscore the importance of multilevel environmental factors in shaping executive system function and WM in youth.

Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth.

Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain Cognitive Development Study® (ABCD). Across both discovery and replication sub-samples, we found that child reports of caregiver monitoring (supervision or regular knowledge of the child's whereabouts) were positively associated with general cognition abilities, after covarying for age, sex, household income, neighborhood deprivation, and parental education. This association was specific to the type of caregiving behavior (caregiver monitoring, but not caregiver warmth), and was most strongly associated with a broad domain of general cognition (but not executive function or learning/memory). Additionally, we found that caregiver monitoring partially mediated the association between household income and cognition, furthering our understanding of how socioeconomic disparities may contribute to disadvantages in cognitive development. Together, these findings underscore the influence of differences in caregiving behavior in shaping youth cognition. RESEARCH HIGHLIGHTS: Caregiver monitoring, but not caregiver warmth, is associated with cognitive performance in youth Caregiver monitoring partially mediates the association between household income and cognition Results replicated across two large matched samples from the Adolescent Brain Cognitive Development Study® (ABCD).

Young children calibrate effort based on the trajectory of their performance.

Learning requires effort, but children cannot try hard at everything. Here, we evaluated whether children use their improvement over time to decide whether to stick with a challenge. To eliminate the effect of individual differences in ability or prior knowledge, we created a novel paradigm that allowed us to surreptitiously control children's performance. Across three preregistered experiments (N = 319, ages 4 to 6 in the United States), we found that children who were given evidence that their performance was improving were more likely to persist on a challenging task than children who were given evidence that their performance was constant, even when final performance was matched. This effect was robust to differing reward contingencies, across in-person and online testing contexts, and was driven by the demotivating effect of constant performance. Our results suggest that young children will be more persistent if they are guided away from too-difficult tasks and toward opportunities that enable steady growth. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Age of Reason: Functional Brain Network Development during Childhood.

Human childhood is characterized by dramatic changes in the mind and brain. However, little is known about the large-scale intrinsic cortical network changes that occur during childhood because of methodological challenges in scanning young children. Here, we overcome this barrier by using sophisticated acquisition and analysis tools to investigate functional network development in children between the ages of 4 and 10 years ([Formula: see text]; 50 female, 42 male). At multiple spatial scales, age is positively associated with brain network segregation. At the system level, age was associated with segregation of systems involved in attention from those involved in abstract cognition, and with integration among attentional and perceptual systems. Associations between age and functional connectivity are most pronounced in visual and medial prefrontal cortex, the two ends of a gradient from perceptual, externally oriented cortex to abstract, internally oriented cortex. These findings suggest that both ends of the sensory-association gradient may develop early, in contrast to the classical theories that cortical maturation proceeds from back to front, with sensory areas developing first and association areas developing last. More mature patterns of brain network architecture, controlling for age, were associated with better visuospatial reasoning abilities. Our results suggest that as cortical architecture becomes more specialized, children become more able to reason about the world and their place in it.SIGNIFICANCE STATEMENT Anthropologists have called the transition from early to middle childhood the "age of reason", when children across cultures become more independent. We employ cutting-edge neuroimaging acquisition and analysis approaches to investigate associations between age and functional brain architecture in childhood. Age was positively associated with segregation between cortical systems that process the external world and those that process abstract phenomena like the past, future, and minds of others. Surprisingly, we observed pronounced development at both ends of the sensory-association gradient, challenging the theory that sensory areas develop first and association areas develop last. Our results open new directions for research into how brains reorganize to support rapid gains in cognitive and socioemotional skills as children reach the age of reason.

Early stressful experiences are associated with reduced neural responses to naturalistic emotional and social content in children.

How do children's experiences relate to their naturalistic emotional and social processing? Because children can struggle with tasks in the scanner, we collected fMRI data while 4-to-11-year-olds watched a short film with positive and negative emotional events, and rich parent-child interactions (n = 70). We captured broad, normative stressful experiences by examining socioeconomic status (SES) and stressful life events, as well as children's more proximal experiences with their parents. For a sub-sample (n = 30), parenting behaviors were measured during a parent-child interaction, consisting of a picture book, a challenging puzzle, and free play with novel toys. We characterized positive parenting behaviors (e.g., warmth, praise) and negative parenting behaviors (e.g., harsh tone, physical control). We found that higher SES was related to greater activity in medial orbitofrontal cortex during parent-child interaction movie events. Negative parenting behaviors were associated with less activation of the ventral tegmental area and cerebellum during positive emotional events. In a region-of-interest analysis, we found that stressful life events and negative parenting behaviors were associated with less activation of the amygdala during positive emotional events. These exploratory results demonstrate the promise of using movie fMRI to study how early experiences may shape emotional, social, and motivational processes.

Individual differences in frontoparietal plasticity in humans.

Neuroplasticity, defined as the brain's potential to change in response to its environment, has been extensively studied at the cellular and molecular levels. Work in animal models suggests that stimulation to the ventral tegmental area (VTA) enhances plasticity, and that myelination constrains plasticity. Little is known, however, about whether proxy measures of these properties in the human brain are associated with learning. Here, we investigated the plasticity of the frontoparietal system by asking whether VTA resting-state functional connectivity and myelin map values (T1w/T2w ratios) predicted learning after short-term training on the adaptive n-back (n = 46, ages 18-25). We found that stronger baseline connectivity between VTA and lateral prefrontal cortex predicted greater improvements in accuracy. Lower myelin map values predicted improvements in response times, but not accuracy. Our findings suggest that proxy markers of neural plasticity can predict learning in humans.

The development of creative search strategies.

How does creativity develop? Creativity is a multi-faceted behavior and thus it is difficult to find measures for creativity that are both precise and comparable across development. Here, we examine the development of creativity using a "creative foraging" task. The task measures different facets of creativity which we compare between 4- to 8-year-old children and adults. We find that compared to adults, children spend a higher percentage of their search exploring, and their exploitation phases are less efficient. Moreover, children orient their search to a different and smaller region of the search space, but within that space they produce more unique creative products. Lastly, as children grow up, their creative products become more adult-like and their uniqueness decreases. Together, these results suggest that creative search changes across development, in the search strategy employed, in how the space of possibilities is navigated, and in what ideas are ultimately chosen.

Functional brain network community structure in childhood: Unfinished territories and fuzzy boundaries.

Adult cortex is organized into distributed functional communities. Yet, little is known about community architecture of children's brains. Here, we uncovered the community structure of cortex in childhood using fMRI data from 670 children aged 9-11 years (48% female, replication sample n=544, 56% female) from the Adolescent Brain and Cognitive Development study. We first applied a data-driven community detection approach to cluster cortical regions into communities, then employed a generative model-based approach called the weighted stochastic block model to further probe community interactions. Children showed similar community structure to adults, as defined by Yeo and colleagues in 2011, in early-developing sensory and motor communities, but differences emerged in transmodal areas. Children have more cortical territory in the limbic community, which is involved in emotion processing, than adults. Regions in association cortex interact more flexibly across communities, creating uncertainty for the model-based assignment algorithm, and perhaps reflecting cortical boundaries that are not yet solidified. Uncertainty was highest for cingulo-opercular areas involved in flexible deployment of cognitive control. Activation and deactivation patterns during a working memory task showed that both the data-driven approach and a set of adult communities statistically capture functional organization in middle childhood. Collectively, our findings suggest that community boundaries are not solidified by middle childhood.

Daily fluctuations in young children's persistence.

Children's behavior changes from day to day, but the factors that contribute to its variability are understudied. We developed a novel repeated measures paradigm to study children's persistence by capitalizing on a task that children complete every day: toothbrushing (N = 81; 48% female; 36-47 months; 80% white, 14% Multiracial, 10% Hispanic, 2% Asian, 1% Black; 1195 observations collected between January 2019 and March 2020). Children brushed longer on days when their parents used more praise (d = .23) and less instruction (d = -.22). Sensitivity to mood, sleep, and parent stress varied across children, suggesting that identifying the factors that shape an individual child's persistence could lead to personalized interventions.

Organizing the Methodological Toolbox: Lessons Learned From Implementing Developmental Methods Online.

Adapting studies typically run in the lab, preschool, or museum to online data collection presents a variety of challenges. The solutions to those challenges depend heavily on the specific questions pursued, the methods used, and the constraints imposed by available technology. We present a partial sample of solutions, discussing approaches we have developed for adapting studies targeting a range of different developmental populations, from infants to school-aged children, and utilizing various online methods such as high-framerate video presentation, having participants interact with a display on their own computer, having the experimenter interact with both the participant and an actor, recording free-play with physical objects, recording infant looking times both offline and live, and more. We also raise issues and solutions regarding recruitment and representativeness in online samples. By identifying the concrete needs of a given approach, tools that meet each of those individual needs, and interfaces between those tools, we have been able to implement many (but not all) of our studies using online data collection during the COVID-19 pandemic. This systematic review aligning available tools and approaches with different methods can inform the design of future studies, in and outside of the lab.

Neurodevelopment of the association cortices: Patterns, mechanisms, and implications for psychopathology.

The human brain undergoes a prolonged period of cortical development that spans multiple decades. During childhood and adolescence, cortical development progresses from lower-order, primary and unimodal cortices with sensory and motor functions to higher-order, transmodal association cortices subserving executive, socioemotional, and mentalizing functions. The spatiotemporal patterning of cortical maturation thus proceeds in a hierarchical manner, conforming to an evolutionarily rooted, sensorimotor-to-association axis of cortical organization. This developmental program has been characterized by data derived from multimodal human neuroimaging and is linked to the hierarchical unfolding of plasticity-related neurobiological events. Critically, this developmental program serves to enhance feature variation between lower-order and higher-order regions, thus endowing the brain's association cortices with unique functional properties. However, accumulating evidence suggests that protracted plasticity within late-maturing association cortices, which represents a defining feature of the human developmental program, also confers risk for diverse developmental psychopathologies.

Evaluating the sensitivity of functional connectivity measures to motion artifact in resting-state fMRI data.

Functional connectivity (FC) networks are typically inferred from resting-state fMRI data using the Pearson correlation between BOLD time series from pairs of brain regions. However, alternative methods of estimating functional connectivity have not been systematically tested for their sensitivity or robustness to head motion artifact. Here, we evaluate the sensitivity of eight different functional connectivity measures to motion artifact using resting-state data from the Human Connectome Project. We report that FC estimated using full correlation has a relatively high residual distance-dependent relationship with motion compared to partial correlation, coherence, and information theory-based measures, even after implementing rigorous methods for motion artifact mitigation. This disadvantage of full correlation, however, may be offset by higher test-retest reliability, fingerprinting accuracy, and system identifiability. FC estimated by partial correlation offers the best of both worlds, with low sensitivity to motion artifact and intermediate system identifiability, with the caveat of low test-retest reliability and fingerprinting accuracy. We highlight spatial differences in the sub-networks affected by motion with different FC metrics. Further, we report that intra-network edges in the default mode and retrosplenial temporal sub-networks are highly correlated with motion in all FC methods. Our findings indicate that the method of estimating functional connectivity is an important consideration in resting-state fMRI studies and must be chosen carefully based on the parameters of the study.