Functional parcellation of the neonatal cortical surface.

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.

Prenatal exposure to maternal social disadvantage and psychosocial stress and neonatal white matter connectivity at birth.

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. Mean diffusivity (MD) and fractional anisotropy (FA) were measured for the dorsal and inferior cingulum bundle (CB), uncinate, and fornix using probabilistic tractography in FSL. Social disadvantage and psychosocial stress were fitted to dMRI parameters using regression models adjusted for infant postmenstrual age at scan and sex. Social disadvantage, but not psychosocial stress, was independently associated with lower MD in the bilateral inferior CB and left uncinate, right fornix, and lower MD and higher FA in the right dorsal CB. Results persisted after accounting for maternal medical morbidities and prenatal drug exposure. In moderation analysis, psychosocial stress was associated with lower MD in the left inferior CB among the lower-to-higher socioeconomic status (SES) (INR ≥ 200%) group, but not the extremely low SES (INR < 200%) group. Increasing access to social welfare programs that reduce the burden of social disadvantage and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways.

Behavioral and psychiatric correlates of brain responses to social feedback.

Maladaptive responses to peer acceptance and rejection arise in numerous psychiatric disorders in adolescence; yet, homogeneity and heterogeneity across disorders suggest common and unique mechanisms of impaired social function. We tested the hypothesis that social feedback is processed similarly to other forms of feedback (e.g., monetary) by examining the correspondence between the brain's response to social acceptance and rejection and behavioral performance on a separate reward and loss task. We also examined the relationship between these brain responses and depression and social anxiety severity. The sample consisted of one hundred and thirteen 16-21-year olds who received virtual peer acceptance/rejection feedback in an event-related potential (ERP) task. We used temporospatial principal component analysis and identified a component consistent with the reward positivity (RewP) or feedback negativity (FN). RewP to social acceptance was not significantly related to reward bias or the FN to social rejection related to loss avoidance. The relationship between RewP and depression severity, while nonsignificant, was of a similar magnitude to prior studies. Exploratory analyses yielded a significant relationship between lower socioeconomic status (SES) and blunted RewP and between lower SES and heightened loss avoidance and blunted reward bias. These findings build on prior work to improve our understanding of the function of the brain's response to social feedback, while also suggesting a pathway for further study, whereby poverty leads to depression via social and reward learning mechanisms.

Sleep and circadian rhythms during pregnancy, social disadvantage, and alterations in brain development in neonates.

Pregnant women in poverty may be especially likely to experience sleep and circadian rhythm disturbances, which may have downstream effects on fetal neurodevelopment. However, the associations between sleep and circadian rhythm disturbances, social disadvantage during pregnancy, and neonatal brain structure remains poorly understood. The current study explored the association between maternal sleep and circadian rhythm disturbances during pregnancy and neonatal brain outcomes, examining sleep and circadian rhythm disturbances as a mediator of the effect of social disadvantage during pregnancy on infant structural brain outcomes. The study included 148 mother-infant dyads, recruited during early pregnancy, who had both actigraphy and neuroimaging data. Mothers' sleep was assessed throughout their pregnancy using actigraphy, and neonates underwent brain magnetic resonance imaging in the first weeks of life. Neonatal structural brain outcomes included cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of the total surface area of the cortex. Neonates of mothers who experienced greater inter-daily deviations in sleep duration had smaller total cortical gray and white matter volumes and reduced cortical surface areas. Neonates of mothers who had higher levels of circadian misalignment and later sleep timing during pregnancy showed smaller subcortical gray matter volumes. Inter-daily deviations in sleep duration during pregnancy mediated the association between maternal social disadvantage and neonatal structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and bring to light the role of chronodisruption as a potential mechanism underlying the deleterious neurodevelopmental effects of prenatal adversity. RESEARCH HIGHLIGHTS: Social disadvantage was associated with sleep and circadian rhythm disturbances during pregnancy, including later sleep schedules, increased variability in sleep duration, circadian misalignment, and a higher proportion of the sleep period spent awake. Maternal sleep and circadian rhythm disturbances during pregnancy were associated with decreased brain volume and reduced cortical surface area in neonates. Maternal inter-daily deviations in sleep duration during pregnancy mediated the association between social disadvantage and neonatal brain volume and cortical surface area.

Network-specific selectivity of functional connections in the neonatal brain.

The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.

Maturation of large-scale brain systems over the first month of life.

The period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child's earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain "growth curve" that could be used to identify atypical brain maturation in infancy.

Social anxiety moderates the association between adolescent irritability and bully perpetration.

BACKGROUND: Preliminary work suggests anxiety moderates the relationship between irritability and bullying. As anxiety increases, the link between irritability and perpetration decreases. We hypothesize that any moderation effect of anxiety is driven by social anxiety symptoms. We sought to explicate the moderating effect of anxiety, while clarifying relations to other aggressive behaviors. METHODS: A sample of adolescents (n = 169, mean = 12.42 years of age) were assessed using clinician rated assessments of anxiety, parent reports of irritability and bullying behaviors (perpetration, generalized aggression, and victimization). Correlations assessed zero-order relations between variables, and regression-based moderation analyses were used to test interactions. Johnson-Neyman methods were used to represent significant interactions. RESULTS: Irritability was significantly related to bullying (r = .403, p < .001). Social, but not generalized, anxiety symptoms significantly moderated the effect of irritability on bully perpetration (t(160) = -2.94, b = -.01, p = .0038, ΔR2 = .0229, F(1, 160) = 8.635). As social anxiety symptoms increase, the link between irritability and perpetration decreases. CONCLUSIONS: Understanding how psychopathology interacts with social behaviors is of great importance. Higher social anxiety is linked to reduced relations between irritability and bullying; however, the link between irritability and other aggression remains positive. Comprehensively assessing how treatment of psychopathology impacts social behaviors may improve future intervention.

Less attention to emotional faces is associated with low empathy and prosociality in 12-to 20-month old infants.

The development of empathy and prosocial behavior begins in infancy and is likely supported by emotion processing skills. The current study explored whether early emerging deficits in emotion processing are associated with disruptions in the development of empathy and prosociality. We investigated this question in a large, diverse sample of 147, 11- to 20-month-old infants (42% female; 61% Black; 67% low socioeconomic status). Infants completed two observational tasks assessing prosocial helping and one task assessing empathy and prosocial comforting behavior. Infants also completed an eye-tracking task assessing engagement and disengagement with negative emotional faces. Infants who attended less to angry, sad, and fearful faces (i.e., by being slower to look at and/or quicker to look away from negative compared to neutral faces) engaged in fewer helping behaviors, and effect sizes were larger when examining infants' attention toward the eye regions of faces. Additionally, infants who were quicker to look away from the eye regions of angry faces, but not the whole face, displayed less empathy and comforting behaviors. Results suggest that as early as 12 months of age, infants' decreased attention toward negative emotional faces, particularly the eye regions, is associated with less empathy and prosociality during a developmental period in which these abilities are rapidly maturing.

Early Emotion Development Intervention Improves Mental Health Outcomes in Low-Income, High-Risk Community Children.

Children living in poverty and facing related forms of adversity are at higher risk for experiencing concurrent and later psychopathology. Although negative psychological outcomes can be improved by enhancing sensitive and responsive caregiving early in development, interventions targeting the caregiver-child dyad are not readily accessible. The present study investigated the feasibility and effectiveness of delivering a shortened eight-session form of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) in-person or remotely as an early intervention for 3-6-year-old children (N = 62) at elevated risk for psychopathology who were growing up in low-income communities. Caregiver-child dyads were randomized to eight-sessions of PCIT-ED or online parenting education. Relative to parenting education, children receiving PCIT-ED exhibited lower externalizing symptoms and functional impairment and more positive peer relationships following the intervention. Findings support the effectiveness of this shortened form of PCIT-ED, delivered in-person or remotely, as an early intervention to improve symptoms of psychopathology and functioning in high-risk children living in poverty.Trial registration Clinicaltrials.gov; NCT04399629.

Benchmarking the generalizability of brain age models: Challenges posed by scanner variance and prediction bias.

Machine learning has been increasingly applied to neuroimaging data to predict age, deriving a personalized biomarker with potential clinical applications. The scientific and clinical value of these models depends on their applicability to independently acquired scans from diverse sources. Accordingly, we evaluated the generalizability of two brain age models that were trained across the lifespan by applying them to three distinct early-life samples with participants aged 8-22 years. These models were chosen based on the size and diversity of their training data, but they also differed greatly in their processing methods and predictive algorithms. Specifically, one brain age model was built by applying gradient tree boosting (GTB) to extracted features of cortical thickness, surface area, and brain volume. The other model applied a 2D convolutional neural network (DBN) to minimally preprocessed slices of T1-weighted scans. Additional model variants were created to understand how generalizability changed when each model was trained with data that became more similar to the test samples in terms of age and acquisition protocols. Our results illustrated numerous trade-offs. The GTB predictions were relatively more accurate overall and yielded more reliable predictions when applied to lower quality scans. In contrast, the DBN displayed the most utility in detecting associations between brain age gaps and cognitive functioning. Broadly speaking, the largest limitations affecting generalizability were acquisition protocol differences and biased brain age estimates. If such confounds could eventually be removed without post-hoc corrections, brain age predictions may have greater utility as personalized biomarkers of healthy aging.

Do general and specific factors of preschool psychopathology predict preadolescent outcomes? A transdiagnostic hierarchical approach.

BACKGROUND: Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general ('p') and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence. METHODS: Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment. RESULTS: A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04-0.15) and functional impairment (ΔR2 = 0.01-0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06-0.15; functional impairment: ΔR2 = 0.05-0.12). CONCLUSIONS: Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.

Editorial: Innovation in child and adolescent mental health interventions.

We are living in a time when children and adolescents are showing higher levels of mental health problems in many countries, and when Child and Adolescent Mental Health Services (CAMHS) in most areas (where they exist at all) are struggling with delivering services to all the young people and families who need them. Many treatment centers respond by restricting the scope of their service, some by excluding younger children, some by focusing on narrower diagnostic groupings, and some by providing online information as a holding strategy.

Associations of observed callous-unemotional behaviors in early childhood with conduct problems and substance use over 14 years.

Callous-unemotional (CU) behaviors (i.e., low concern and active disregard for others) uniquely predict severe conduct problems and substance use when present by late childhood. Less is known about the predictive utility of CU behaviors displayed in early childhood, when morality is developing and interventions may be more effective. Children aged 4-7 years (N = 246; 47.6% girls) completed an observational task wherein they were encouraged to tear an experimenter's valued photograph, and blind raters coded children's displayed CU behaviors. During the next 14 years, children's conduct problems (i.e., oppositional defiant and conduct symptoms) and age of onset of substance use were assessed. Compared to children displaying fewer CU behaviors, children displaying greater CU behaviors were 7.61 times more likely to meet criteria for a conduct disorder (n = 52) into early adulthood (95% CI, 2.96-19.59; p = <.0001), and their conduct problems were significantly more severe. Greater CU behaviors were associated with earlier onset of substance use (B = -.69, SE = .32, t = -2.14, p = .036). An ecologically valid observed indicator of early CU behavior was associated with substantially heightened risk for conduct problems and earlier onset substance use into adulthood. Early CU behavior is a powerful risk marker identifiable using a simple behavioral task which could be used to target children for early intervention.

Developmental trajectories of anger and sadness dysregulation in childhood differentially predict later borderline symptoms.

Difficulties with emotion regulation are integral to borderline personality disorder (BPD) and its hypothesized developmental pathway. Here, we prospectively assess trajectories of emotion processing across childhood, how BPD symptoms impact these trajectories, and whether developmental changes are transdiagnostic or specific to BPD, as major depressive (MDD) and conduct disorders (CD) are also characterized by emotion regulation difficulties. This study included 187 children enriched for those with early symptoms of depression and disruptive behaviors from a longitudinal study. We created multilevel models of multiple components of emotional processing from mean ages 9.05 to 18.55 years, and assessed the effect of late adolescent BPD, MDD, and CD symptoms on these trajectories. Linear trajectories of coping with sadness and anger, and quadratic trajectories of dysregulated expressions of sadness and anger were transdiagnostic, but also exhibited independent relationships with BPD symptoms. Only inhibition of sadness was related to BPD symptoms. The quadratic trajectories of poor emotional awareness and emotional reluctance were also independently related to BPD. Findings support examining separable components of emotion processing across development as potential precursors to BPD, underscoring the importance of understanding these trajectories as not only a marker of potential risk but also potential targets for prevention and intervention.

Developmental pathways from preschool temper tantrums to later psychopathology.

Temper tantrums are sudden, overt negative emotional displays that are disproportionate to the eliciting event. Research supports that severe temper tantrums during the preschool period are associated with preschool psychopathology, but few studies have identified which characteristics of preschool tantrums are predictive of distal psychopathological outcomes in later childhood and adolescence. To examine this question, we used a prospective, longitudinal dataset enriched for early psychopathology. Participants (N = 299) included 3-to 6-year-old children (47.8% female) assessed for tantrums and early childhood psychopathology using diagnostic interviews and then continually assessed using diagnostic interviews over 10 subsequent time points throughout childhood and adolescence. We identified two unique groupings of tantrum behaviors: aggression towards others/objects (e.g., hitting others) and aggression towards self (e.g., hitting self). While both types of tantrum behaviors were associated with early childhood psychopathology severity, tantrum behaviors characterized by aggression towards self were more predictive of later psychopathology. Children displaying high levels of both types of tantrum behaviors had more severe externalizing problems during early childhood and more severe depression and oppositional defiant disorder across childhood and adolescence. Findings suggest that tantrum behaviors characterized by aggression towards self are particularly predictive of later psychopathology.

Predictive Utility of Irritability "In Context": Proof-of-Principle for an Early Childhood Mental Health Risk Calculator.

OBJECTIVE: We provide proof-of-principle for a mental health risk calculator advancing clinical utility of the irritability construct for identification of young children at high risk for common, early onsetting syndromes. METHOD: Data were harmonized from two longitudinal early childhood subsamples (total N = 403; 50.1% Male; 66.7% Nonwhite; Mage = 4.3 years). The independent subsamples were clinically enriched via disruptive behavior and violence (Subsample 1) and depression (Subsample 2). In longitudinal models, epidemiologic risk prediction methods for risk calculators were applied to test the utility of the transdiagnostic indicator, early childhood irritability, in the context of other developmental and social-ecological indicators to predict risk of internalizing/externalizing disorders at preadolescence (Mage = 9.9 years). Predictors were retained when they improved model discrimination (area under the receiver operating characteristic curve [AUC] and integrated discrimination index [IDI]) beyond the base demographic model. RESULTS: Compared to the base model, the addition of early childhood irritability and adverse childhood experiences significantly improved the AUC (0.765) and IDI slope (0.192). Overall, 23% of preschoolers went on to develop a preadolescent internalizing/externalizing disorder. For preschoolers with both elevated irritability and adverse childhood experiences, the likelihood of an internalizing/externalizing disorder was 39-66%. CONCLUSIONS: Predictive analytic tools enable personalized prediction of psychopathological risk for irritable young children, holding transformative potential for clinical translation.

Testosterone and hippocampal trajectories mediate relationship of poverty to emotion dysregulation and depression.

There is robust evidence that early poverty is associated with poor developmental outcomes, including impaired emotion regulation and depression. However, the specific mechanisms that mediate this risk are less clear. Here we test the hypothesis that one pathway involves hormone mechanisms (testosterone and DHEA) that contribute to disruption of hippocampal brain development, which in turn contributes to perturbed emotion regulation and subsequent risk for depression. To do so, we used data from 167 children participating in the Preschool Depression Study, a longitudinal study that followed children from preschool (ages 3 to 5 y) to late adolescence, and which includes prospective assessments of poverty in preschool, measures of testosterone, DHEA, and hippocampal volume across school age and adolescence, and measures of emotion regulation and depression in adolescence. Using multilevel modeling and linear regression, we found that early poverty predicted shallower increases of testosterone, but not DHEA, across development, which in turn predicted shallower trajectories of hippocampal development. Further, we found that early poverty predicted both impaired emotion regulation and depression. The relationship between early poverty and self-reported depression in adolescence was explained by serial mediation through testosterone to hippocampus to emotion dysregulation. There were no significant interactions with sex. These results provide evidence about a hormonal pathway by which early poverty may contribute to disrupted brain development and risk for mental health problems later in life. Identification of such pathways provide evidence for potential points of intervention that might help mitigate the impact of early adversity on brain development.

Parent-child psychotherapy targeting emotion development: unpacking the impact of parental depression on child, parenting and engagement outcomes.

Depression in early childhood increases risk of psychopathology and impairment across the lifespan. Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) effectively treats depression and improves functioning in preschoolers. Parental depression has been associated with inconsistent parenting, depression onset and maintenance in offspring, and decreased treatment efficacy for youth. Given the intensity of parent involvement in PCIT-ED, this secondary data analysis aimed to evaluate parental depression severity (i.e., Beck Depression Inventory-II Total Score; BDI-II) as a moderator and predictor of child, parenting, and engagement outcomes, within the context of a randomized trial. Children (N = 229; ages 3-6.11) with early childhood depression and a consenting caregiver were randomly assigned to receive PCIT-ED or Waitlist (WL). Moderation results supported the superiority of PCIT-ED over WL on child and parenting outcomes, independent of parent-reported BDI-II at baseline (p ≥ 0.684 and p ≥ 0.476, respectively). BDI-II did not significantly predict child (p ≥ 0.836), parenting (p ≥ 0.114) or engagement (p ≥ 0.114) outcomes. Finally, BDI-II did not surpass chance in predicting whether children would maintain a depression diagnosis after PCIT-ED (AUC = 0.530) or prematurely terminate treatment (AUC = 0.545). Our results suggest that PCIT-ED is not contraindicated by minimal-to-moderate symptoms of depression in parents. Taken together with previous reports, PCIT-ED may indeed be a particularly beneficial treatment choice for this population. Further research in samples with more severe parental depression is needed. ClinicalTrials.gov identifier: NCT02076425.

Maternal emotional intelligence and negative parenting affect are independently associated with callous-unemotional traits in preschoolers.

Deficits in emotion intelligence (EI) are a key component of early-childhood callous-unemotional (CU) traits. Children's EI may be influenced by their mother's EI through both familial genetic and environmental mechanisms; however, no study has directly tested the role of maternal EI in the development of CU traits. This study investigated whether maternal EI had a direct relationship with children's CU traits when controlling for the potential influence of parenting affect and other psychiatric diagnoses. Mothers and their 3- to 5-year-old preschoolers (N = 200) were recruited as part of a parent-child interaction-emotion development therapy treatment trial for preschool clinical depression and comorbid psychopathology. Using data collected prior to treatment, regression models tested whether maternal EI was related to children's CU traits, which specific aspects of maternal EI were most strongly associated with CU traits, and whether associations held after accounting for observed parenting affect. Maternal EI (p < 0.005), specifically the ability to understand others' emotions (p < 0.01), was significantly associated with children's CU traits. This relationship was specific, as maternal EI did not predict depression or oppositional defiant disorder. Both maternal EI and observed negative parenting affect were independently and significantly related to CU traits (p < 0.05) in a combined model. Given that maternal EI and observed negative parenting affect were independent predictors of CU traits in preschoolers with comorbid depression, findings suggest that current treatments for CU traits that focus solely on improving parenting could be made more effective by targeting maternal EI and helping mothers better model emotional competence.

New Directions in Child Psychiatry: Shaping Neurodevelopmental Trajectories.

Historically, the field of child psychiatry has lagged behind the field of general psychiatry in terms of research innovations and the availability of empirically supported treatment modalities. However, over the last two decades there has been increasing interest in and research focused on the developmental origins of mental disorders examining both neurobiological and psychosocial etiologies.1 This has catalyzed the field leading to advances in understanding the developmental psychopathology of mental disorders and the generation of novel early interventions that have shown significant promise.2-4 Further, catalyzing this effort is new data demonstrating the powerful impact of psychosocial forces on neurodevelopment. New methodologies and discoveries in the basic areas of early childhood developmental psychology have led to a greater appreciation for the emotional and cognitive sophistication of children in the first three years of life. Advances in methods to understand preverbal children's emotional and attentional responses (through measures of eye gaze and suck for example) as well as observational methods to glean a variety of mental health relevant behaviors early in life (e.g. behavioral inhibition, pro-social behaviors and social motivation) have further elucidated and validated these capacities. In addition, measures of neural function using electroencephalogram and evoked response potentials (EEG/ERP) and functional magnetic resonance imaging (fMRI) as early as the neonatal period, with many analysis methods developed at WUSTL, have further informed this domain providing new insight into early brain and behavioral relationships as well as how intervention impact brain function.5-7.