Exploring the Association Between EEG Microstates During Resting-State and Error-Related Activity in Young Children.

The error-related negativity (ERN) is a negative deflection in the electroencephalography (EEG) waveform at frontal-central scalp sites that occurs after error commission. The relationship between the ERN and broader patterns of brain activity measured across the entire scalp that support error processing during early childhood is unclear. We examined the relationship between the ERN and EEG microstates - whole-brain patterns of dynamically evolving scalp potential topographies that reflect periods of synchronized neural activity - during both a go/no-go task and resting-state in 90, 4-8-year-old children. The mean amplitude of the ERN was quantified during the -64 to 108 millisecond (ms) period of time relative to error commission, which was determined by data-driven microstate segmentation of error-related activity. We found that greater magnitude of the ERN associated with greater global explained variance (GEV; i.e., the percentage of total variance in the data explained by a given microstate) of an error-related microstate observed during the same -64 to 108 ms period (i.e., error-related microstate 3), and to greater anxiety risk as measured by parent-reported behavioral inhibition. During resting-state, six data-driven microstates were identified. Both greater magnitude of the ERN and greater GEV values of error-related microstate 3 associated with greater GEV values of resting-state microstate 4, which showed a frontal-central scalp topography. Source localization results revealed overlap between the underlying neural generators of error-related microstate 3 and resting-state microstate 4 and canonical brain networks (e.g., ventral attention) known to support the higher-order cognitive processes involved in error processing. Taken together, our results clarify how individual differences in error-related and intrinsic brain activity are related and enhance our understanding of developing brain network function and organization supporting error processing during early childhood.

Microstate Analysis of Continuous Infant EEG: Tutorial and Reliability.

Microstate analysis of resting-state EEG is a unique data-driven method for identifying patterns of scalp potential topographies, or microstates, that reflect stable but transient periods of synchronized neural activity evolving dynamically over time. During infancy - a critical period of rapid brain development and plasticity - microstate analysis offers a unique opportunity for characterizing the spatial and temporal dynamics of brain activity. However, whether measurements derived from this approach (e.g., temporal properties, transition probabilities, neural sources) show strong psychometric properties (i.e., reliability) during infancy is unknown and key information for advancing our understanding of how microstates are shaped by early life experiences and whether they relate to individual differences in infant abilities. A lack of methodological resources for performing microstate analysis of infant EEG has further hindered adoption of this cutting-edge approach by infant researchers. As a result, in the current study, we systematically addressed these knowledge gaps and report that most microstate-based measurements of brain organization and functioning except for transition probabilities were stable with four minutes of video-watching resting-state data and highly internally consistent with just one minute. In addition to these results, we provide a step-by-step tutorial, accompanying website, and open-access data for performing microstate analysis using a free, user-friendly software called Cartool. Taken together, the current study supports the reliability and feasibility of using EEG microstate analysis to study infant brain development and increases the accessibility of this approach for the field of developmental neuroscience.

Children's exposure to chemical contaminants: Demographic disparities and associations with the developing basal ganglia.

Children are regularly exposed to chemical contaminants that may influence brain development. However, relatively little is known about how these contaminants impact the developing human brain. Here, we combined silicone wristband exposure assessments with neuroimaging for the first time to examine how chemical contaminant mixtures are associated with the developing basal ganglia-a brain region key for the healthy development of emotion, reward, and motor processing, and which may be particularly susceptible to contaminant harm. Further, we examined demographic disparities in exposures to clarify which children were at highest risk for any contaminant-associated neurobiological changes. Participants included 62 community children (average age 7.00 years, 53% female, 66% White) who underwent structural neuroimaging to provide data on their basal ganglia structure and wore a silicone wristband for seven days to track their chemical contaminant exposure. 45 chemical contaminants-including phthalates and their alternatives, brominated flame retardants, organophosphate esters, pesticides, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls-were detected in over 75% of wristbands. Notable demographic disparities in exposure were present, such that Non-White and lower-income children were more exposed to several contaminants. Exposure to chemical contaminant mixtures was not associated with overall basal ganglia volume; however, two organophosphate esters (2IPPDPP and 4IPPDPP) were both associated with a larger globus pallidus, a basal ganglia sub-region. Results highlight demographic disparities in exposure and suggest possible risks to a brain region key for healthy emotional development.

Social origins of self-regulated attention during infancy and their disruption in autism spectrum disorder: Implications for early intervention.

To understand the complex relationships between autism spectrum disorder (ASD) and other frequently comorbid conditions, a growing number of studies have investigated the emergence of ASD during infancy. This research has suggested that symptoms of ASD and highly related comorbid conditions emerge from complex interactions between neurodevelopmental vulnerabilities and early environments, indicating that developing treatments to prevent ASD is highly challenging. However, it also suggests that attenuating the negative effects of ASD on future development once identified is possible. The present paper builds on this by conceptualizing developmental delays in nonsocial skills as the potential product of altered caregiver-infant interactions following the emergence of ASD during infancy. And, following emerging findings from caregiver-infant dyadic head-mounted eye-tracking (D-ET) research, it also suggests that a multiple pathway model of joint attention can provide mechanistic insights into how ASD alters the ability of caregiver and infant to create a context for infant learning. The potential for this view to inform early intervention is further discussed and illustrated through D-ET data collected prior to and following a brief, parent-mediated intervention for infant ASD. While promising, further research informing how a multiple pathway model of joint attention can inform ASD early intervention is needed.

The Lifespan Human Connectome Project in Development: A large-scale study of brain connectivity development in 5-21 year olds.

Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300 + healthy human participants, ages 5-21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9-17 years). Brain imaging sessions are acquired on a 3 T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.

Continuity and stability of preschool depression from childhood through adolescence and following the onset of puberty.

BACKGROUND: A growing body of research now supports the validity, clinical significance, and long-term negative impact of depression occurring during the preschool period. However, the prospective continuity of depressive symptoms and risk for major depressive disorder (MDD) from childhood through adolescence for preschoolers experiencing this highly impairing disorder remains unexplored. Such information is likely to be critical for understanding the developmental continuity of preschool depression and whether it continues to be a salient risk factor for an MDD diagnosis following the transition into adolescence and the onset of biological changes associated with it (i.e., puberty). METHODS: Subjects were participants in the Preschool Depression Study conducted at the Early Emotional Development Program at Washington University School of Medicine in St. Louis. Subjects and their parents completed baseline assessments that included comprehensive measures of psychopathology and development at baseline and up to 9 follow-up assessments between 2003 and 2017. N = 279 subjects had diagnostic and clinical data available for the preschool period and the early pubertal and/or later pubertal periods and were included in the analyses. There were N = 275 subjects assessed during the early pubertal period and N = 184 subjects assessed during the later pubertal period. RESULTS: Preschool depression was a highly salient predictor of prepubertal and mid-to-post pubertal MDD. Across all modeled time points children with a history of preschool depression continued to demonstrate elevated levels of depressive symptoms from childhood through adolescence, suggesting a heightened trajectory of depressive symptoms relative to their same age peers. CONCLUSION: Findings from the current study suggest that children with a history of preschool depression follow a trajectory of depression severity elevated relative to their same age peers from childhood through adolescence but with a similar shape over time. They also support the homotypic continuity of preschool depression into adolescence and the onset of puberty.

HPA axis genetic variation, pubertal status, and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children.

Accumulating evidence suggests a role for stress exposure, particularly during early life, and for variation in genes involved in stress response pathways in neural responsivity to emotional stimuli. Understanding how individual differences in these factors predict differences in emotional responsivity may be important for understanding both normative emotional development and for understanding the mechanisms underlying internalizing disorders, like anxiety and depression, that have often been related to increased amygdala and hippocampus responses to negatively valenced emotional stimuli. The present study examined whether stress exposure and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predict individual differences in amygdala and hippocampus responses to fearful vs. neutral faces in school-age children (7-12 year olds; N = 107). Experience of more stressful and traumatic life events predicted greater left amygdala responses to negative emotional stimuli. Genetic profile scores interacted with sex and pubertal status to predict amygdala and hippocampus responses. Specifically, genetic profile scores were a stronger predictor of amygdala and hippocampus responses among pubertal vs. prepubertal children where they positively predicted responses to fearful faces among pubertal girls and positively predicted responses to neutral faces among pubertal boys. The current results suggest that genetic and environmental stress-related factors may be important in normative individual differences in responsivity to negative emotional stimuli, a potential mechanism underlying internalizing disorders. Further, sex and pubertal development may be key moderators of the effects of stress-system genetic variation on amygdala and hippocampus responsivity, potentially relating to sex differences in stress-related psychopathology.

Maternal support in early childhood predicts larger hippocampal volumes at school age.

Early maternal support has been shown to promote specific gene expression, neurogenesis, adaptive stress responses, and larger hippocampal volumes in developing animals. In humans, a relationship between psychosocial factors in early childhood and later amygdala volumes based on prospective data has been demonstrated, providing a key link between early experience and brain development. Although much retrospective data suggests a link between early psychosocial factors and hippocampal volumes in humans, to date there has been no prospective data to inform this potentially important public health issue. In a longitudinal study of depressed and healthy preschool children who underwent neuroimaging at school age, we investigated whether early maternal support predicted later hippocampal volumes. Maternal support observed in early childhood was strongly predictive of hippocampal volume measured at school age. The positive effect of maternal support on hippocampal volumes was greater in nondepressed children. These findings provide prospective evidence in humans of the positive effect of early supportive parenting on healthy hippocampal development, a brain region key to memory and stress modulation.

Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype and stressful life events interact to predict preschool-onset depression: a replication and developmental extension.

BACKGROUND: Scientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings highlight the need for further research. Converging evidence suggests that the effects of 5-HTTLPR genotype may be neurodevelopmental in origin, but we are not aware of empirical studies that have investigated whether the 5-HTTLPR genotype × SLE interaction predicts preschool-onset depression (PO-MDD), the earliest validated form of depression. METHODS: Children (n = 234) aged 3-5 were recruited for a longitudinal study designed to examine PO-MDD. In a comprehensive baseline assessment, the child's primary caregivers completed questionnaires and were interviewed about their child's behaviors, psychiatric symptoms, and exposure to SLEs. RESULTS: A 5-HTTLPR × SLEs interaction emerged, such that children homozygous for the short allele were more susceptible to depression in the context of elevated SLE than long allele carriers. In contrast, at low SLE exposure, short allele homozygotes had fewer depressive symptoms. The data were best fit by a plasticity model with a substantial reduction in fit by diathesis-stress models. CONCLUSIONS: Extending studies in adult and adolescent populations, these data suggest that 5-HTTLPR genotype may provide plasticity to environmental influence, for better or worse. Specifically, children homozygous for the short allele were more susceptible to the depressogenic effects of SLEs but benefitted, in the form of reduced depressive symptoms, in the context of relatively benign environmental conditions (i.e. relatively low SLE exposure). These data highlight the importance of examining gene × environment interactions across development, environment, and outcome but should be interpreted cautiously given the small sample size.

Dimensions of Depressive Symptoms in Young Children: Factor Analysis of the Preschool Feelings Checklist-Scale.

The current study is an investigation of the dimensionality of the Preschool Feelings Checklist-Scale (PFC-S), a caregiver-report questionnaire of early childhood depressive symptom severity. Caregivers of 450 young children, ages 3-8 years (M = 5.62, SD = 0.95; 49% female; 7% Hispanic; 66% White), completed the PFC-S and questionnaires on child emotion regulation and expression and self-reported depressive symptomatology. Confirmatory factor analyses indicated that a one-factor structure did not adequately fit the current PFC-S data. Using exploratory factor analysis, a three-factor structure emerged as interpretable and structurally sound, yielding reliable factors related to social and behavioral anhedonia, emotional and behavioral dysregulation, and excessive guilt and sadness. This factor structure showed configural and scalar invariance across preschool-aged and early middle childhood-aged children as well as children assigned male and female sex at birth. Correlations between the three factors and constructs related to depression suggested preliminary construct validity. The current study provides initial evidence for a multidimensional structure of the PFC-S and improves our understanding of early childhood depressive symptoms.

Towards the study of functional brain development in depression: an Interactive Specialization approach.

Depression is a significant and impairing mood disorder with onset possible as early as age 3 and into adulthood. Given this varying pattern of age of onset, identifying the relationship between brain development and depression across the lifespan has proven elusive. This review identifies some of the factors that may have limited the advancement of our knowledge in this area and discusses how synthesizing established models of depression and normative brain development may help to overcome them. More specifically, it is suggested that current neurobiological models of depression fail to account for the developmental variance associated with early neural network development and the potential influence of experience on this process. The utility of applying an established framework of normative brain development to this topic is described and its potential utility for conceptualizing the influence of depression on brain function across the life span is addressed. Future directions including longitudinal neuroimaging studies of early onset depression and groups at risk for this disorder are proposed.

Functional brain activation to emotional and nonemotional faces in healthy children: evidence for developmentally undifferentiated amygdala function during the school-age period.

The amygdala is a key region in emotion processing. In particular, fMRI studies have demonstrated that the amygdala is active during the viewing of emotional faces. Previous research has consistently found greater amygdala responses to fearful than to neutral faces in adults, convergent with a focus in the animal literature on the amygdala's role in fear processing. Studies have shown that the amygdala also responds differentially to other facial emotion types in adults. Yet the literature regarding when this differential amygdala responsivity develops is limited and mixed. Thus, the goal of the present study was to examine amygdala responses to emotional and neutral faces in a relatively large sample of healthy school-age children (N = 52). Although the amygdala was active in response to emotional and neutral faces, the results did not support the hypothesis that the amygdala responds differentially to emotional faces in 7- to 12-year-old children. Nonetheless, amygdala activity was correlated with the severity of subclinical depression symptoms and with emotional regulation skills. Additionally, sex differences were observed in frontal, temporal, and visual regions, as well as effects of pubertal development in visual regions. These findings suggest important differences in amygdala reactivity in childhood.

Structural-functional correlations between hippocampal volume and cortico-limbic emotional responses in depressed children.

Although hippocampal atrophy and altered functional brain responses to emotional stimuli have been found in major depressive disorder (MDD), the relationship between the two is not yet well understood. The present study focused on children with and without a history of preschool onset MDD (PO-MDD) and directly examined the relations between hippocampal volume and functional brain activation to affect-eliciting stimuli. Children completed annual diagnostic assessments starting at preschool. When children were school-aged, high-resolution structural MRI and task-related functional MRI data were acquired from N = 64 nonmedicated children. During fMRI, subjects were shown emotional faces. Results from the total sample indicated that smaller bilateral hippocampal volumes were associated with greater cortico-limbic (e.g., amygdala, hippocampus, dorsolateral prefrontal cortex) activation to sad or negative faces versus neutral faces. Left hippocampal volume was negatively associated with the cortico-limbic activation in both the PO-MDD and healthy children. Right hippocampal volume was negatively correlated with amygdala responses in the PO-MDD group, but not in the healthy comparison group. These findings suggest that there may be important interrelationships between reduced hippocampal volume and hyperactivation of brain responses in children, both those with and those without a history of PO-MDD.

Associations between pre-pandemic authoritative parenting, pandemic stressors, and children's depression and anxiety at the initial stage of the COVID-19 pandemic.

Large-scale changes due to the Novel Coronavirus (COVID-19) pandemic negatively affected children's mental health. Prior research suggests that children's mental health problems during the pandemic may have been concurrently attenuated by an authoritative parenting style and exacerbated by family stress. However, there is a gap in the literature investigating these mechanisms and whether pre-pandemic authoritative parenting had a lasting positive influence on children's mental health while they were exposed to pandemic-related family stressors. The current study begins to fill this gap by investigating these unique relationships in a sample of 106 4-8 year old children (51% female). Before the pandemic, caregivers completed questionnaires on their parenting style and their children's depression and anxiety symptoms. Shortly after the onset of COVID-19's stay-at-home mandate, parents answered questionnaires about their children's depression and anxiety symptoms and pandemic-related family stressors. Child depression and anxiety symptom severity increased. Higher levels of pandemic-related family stress were associated with increases only in child anxiety scores. Further, greater endorsement of a pre-pandemic authoritative parenting style was associated with smaller changes only in child depression scores. Study findings elucidate unique and complex associations between young children's anxiety and depression symptoms severity and pre-pandemic parenting and pandemic-related family stressors.

Exploring the association between EEG microstates during resting-state and error-related activity in young children.

The error-related negativity (ERN) is a negative deflection in the electroencephalography (EEG) waveform at frontal-central scalp sites that occurs after error commission. The relationship between the ERN and broader patterns of brain activity measured across the entire scalp that support error processing during early childhood is unclear. We examined the relationship between the ERN and EEG microstates - whole-brain patterns of dynamically evolving scalp potential topographies that reflect periods of synchronized neural activity - during both a go/no-go task and resting-state in 90, 4-8-year-old children. The mean amplitude of the ERN was quantified during the - 64 to 108 millisecond (ms) period of time relative to error commission, which was determined by data-driven microstate segmentation of error-related activity. We found that greater magnitude of the ERN associated with greater global explained variance (GEV; i.e., the percentage of total variance in the data explained by a given microstate) of an error-related microstate observed during the same - 64 to 108 ms period (i.e., error-related microstate 3), and to greater parent-report-measured anxiety risk. During resting-state, six data-driven microstates were identified. Both greater magnitude of the ERN and greater GEV values of error-related microstate 3 associated with greater GEV values of resting-state microstate 4, which showed a frontal-central scalp topography. Source localization results revealed overlap between the underlying neural generators of error-related microstate 3 and resting-state microstate 4 and canonical brain networks (e.g., ventral attention) known to support the higher-order cognitive processes involved in error processing. Taken together, our results clarify how individual differences in error-related and intrinsic brain activity are related and enhance our understanding of developing brain network function and organization supporting error processing during early childhood.

Toxicant exposure and the developing brain: A systematic review of the structural and functional MRI literature.

Youth worldwide are regularly exposed to pollutants and chemicals (i.e., toxicants) that may interfere with healthy brain development, and a surge in MRI research has begun to characterize the neurobiological consequences of these exposures. Here, a systematic review following PRISMA guidelines was conducted on developmental MRI studies of toxicants with known or suspected neurobiological impact. Associations were reviewed for 9 toxicant classes, including metals, air pollution, and flame retardants. Of 1264 identified studies, 46 met inclusion criteria. Qualitative synthesis revealed that most studies: (1) investigated air pollutants or metals, (2) assessed exposures prenatally, (3) assessed the brain in late middle childhood, (4) took place in North America or Western Europe, (5) drew samples from existing cohort studies, and (6) have been published since 2017. Given substantial heterogeneity in MRI measures, toxicant measures, and age groups assessed, more research is needed on all toxicants reviewed here. Future studies should also include larger samples, employ personal exposure monitoring, study independent samples in diverse world regions, and assess toxicant mixtures.

Electrical brain activations in young children during a probabilistic reward-learning task are associated with behavioral strategy.

Both adults and children learn through feedback which events and choices in the environment are associated with higher probability of reward. This probability reward-learning ability is thought to be supported by the development of fronto-striatal reward circuits. Recent developmental studies have applied computational models of reward learning to investigate such learning in children. However, there has been limited development of task tools capable of measuring the cascade of neural reward-learning processes in children. Using a child-version of a probabilistic reward-learning task while recording event-related-potential (ERP) measures of electrical brain activity, this study examined key processes of reward learning in preadolescents (n=30), namely: (1) reward-feedback sensitivity, as measured by the early reward-related frontal ERP positivity, (2) rapid attentional shifting of processing toward favored visual stimuli, as measured by the N2pc component, and (3) longer-latency attention-related responses to reward feedback as a function of behavior strategies (i.e., Win-Stay-Lose-Shift), as measured by the central-parietal P300. Consistent with our prior work in adults, the behavioral findings indicate that preadolescents could learn stimulus-reward outcome associations, but at varying levels of performance. Neurally, poor preadolescent learners (those with slower learning rates) showed greater reward-related positivity amplitudes relative to good learners, suggesting greater reward sensitivity. We also found attention shifting towards to-be-chosen stimuli, as evidenced by the N2pc, but not to more highly rewarded stimuli. Lastly, we found an effect of behavioral learning strategies (i.e., Win-Stay-Lose-Shift) on the feedback-locked P300 over the parietal cortex. These findings provide novel insights into the key neural processes underlying reinforcement learning in preadolescents.

Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity.

Previous studies have suggested atypically enhanced activity of visual cortex during language processing in autism spectrum disorder (ASD). However, it remains unclear whether visual cortical participation reflects isolated processing within posterior regions or functional cooperation with distal brain regions, such as left inferior frontal gyrus (LIFG). We addressed this question using functional connectivity MRI (fcMRI) and structural equation modeling in 14 adolescents and adults with ASD and 14 matched typically developing (TD) participants. Data were analyzed to isolate low-frequency intrinsic fluctuations, by regressing out effects of a semantic decision task. For a right extrastriate seed derived from the strongest cluster of atypical activation in the ASD group, widespread effects of increased connectivity in prefrontal and medial frontal lobes bilaterally were observed for the ASD group, compared to the TD group. A second analysis for a seed in LIFG, derived from pooled activation effects in both groups, also yielded widespread effects of overconnectivity in the ASD group, especially in temporal lobes. Structural equation modeling showed that whereas right extrastriate cortex did not impact function of language regions (left and right IFG, left middle temporal gyrus) in the TD model, it was an integral part of a language circuit in the ASD group. These results suggest that atypical extrastriate activation during language processing in ASD reflects integrative (not isolated) processing. Furthermore, our findings are inconsistent with previous reports of functional underconnectivity in ASD, probably related to removal of task effects required to isolate intrinsic low-frequency fluctuations.

Default mode network connectivity in children with a history of preschool onset depression.

BACKGROUND: Atypical Default Mode Network (DMN) functional connectivity has been previously reported in depressed adults. However, there is relatively little data informing the developmental nature of this phenomenon. The current case-control study examined the DMN in a unique prospective sample of school-age children with a previous history of preschool depression. METHODS: DMN functional connectivity was assessed using resting state functional connectivity magnetic resonance imaging data and the posterior cingulate (PCC) as a seed region of interest. Thirty-nine medication naïve school age children (21 with a history of preschool depression and 18 healthy peers) and their families who were ascertained as preschoolers and prospectively assessed over at least 4 annual waves as part of a federally funded study of preschool depression were included. RESULTS: Decreased connectivity between the PCC and regions within the middle temporal gyrus (MTG), inferior parietal lobule, and cerebellum was found in children with known depression during the preschool period. Increased connectivity between the PCC and regions within the subgenual and anterior cingulate cortices and anterior MTG bilaterally was also found in these children. Additionally, a clinically relevant 'brain-behavior' relationship between atypical functional connectivity of the PCC and disruptions in emotion regulation was identified. CONCLUSIONS: To our knowledge, this is the first study to examine the DMN in children known to have experienced the onset of a clinically significant depressive syndrome during preschool. Results suggest that a history of preschool depression is associated with atypical DMN connectivity. However, longitudinal studies are needed to clarify whether the current findings of atypical DMN connectivity are a precursor or a consequence of preschool depression.

Reduced cortical surface area globally and in reward-related cortex is associated with elevated depressive symptoms in preschoolers.

BACKGROUND: Elevated depressive symptoms in early childhood strongly predict depression onset in youth. Nevertheless, little is known about the neural correlates of these symptoms, information that is key for understanding the early development of depression. As a result, the present study conducted a novel investigation of the association between cortical structure and depressive symptoms in preschoolers. METHODS: Forty-six preschool age children (Mage = 5.90, SD = 0.75), some (N = 15) at high risk for depression, participated in the study. Data included parent-report of child depressive symptoms and measures of child whole brain and regional cortical structure acquired via 3T MRI. RESULTS: After adjustment for maternal depression, socio-economic status, child age, child sex, and intracranial volume, reduced total cortical surface area and reduced surface area of the lateral orbitofrontal cortex were associated with elevated depressive symptoms. Cortical thickness was not associated with depressive symptoms. LIMITATIONS: The present data are cross-sectional, limiting any causal interpretations. CONCLUSIONS: Results suggest that reduced cortical surface area, rather than thickness, is a neural correlate of depressive symptoms in preschoolers. Findings highlight the importance of surface area in reward processing regions (i.e., lateral orbitofrontal cortex) in particular. The present results provide novel insight into early emerging associations between brain structure and features of depression in young children and underscore early childhood as an important developmental period for understanding depression.