Developmental foundations of physiological dynamics among mother-infant dyads: The role of newborn neurobehavior.

This study tested whether newborn attention and arousal provide a foundation for the dynamics of respiratory sinus arrhythmia (RSA) in mother-infant dyads. Participants were 106 mothers (Mage  = 29.54) and their 7-month-old infants (55 males and 58 White and non-Hispanic). Newborn attention and arousal were measured shortly after birth using the NICU Network Neurobehavioral Scale. Higher newborn arousal predicted a slower return of infant RSA to baseline. Additionally, greater newborn attention predicted mothers' slower return to baseline RSA following the still-face paradigm, and this effect only held for mothers whose infants had lower newborn arousal. These findings suggest that newborn neurobehavior, measured within days of birth, may contribute to later mother-infant physiological processes while recovering from stress.

Electroencephalogram aperiodic power spectral slope can be reliably measured and predicts ADHD risk in early development.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n = 69, 1-month-old) and adolescents (n = 262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

Spectral parameterization for studying neurodevelopment: How and why.

A growing body of literature suggests that the explicit parameterization of neural power spectra is important for the appropriate physiological interpretation of periodic and aperiodic electroencephalogram (EEG) activity. In this paper, we discuss why parameterization is an imperative step for developmental cognitive neuroscientists interested in cognition and behavior across the lifespan, as well as how parameterization can be readily accomplished with an automated spectral parameterization ("specparam") algorithm (Donoghue et al., 2020a). We provide annotated code for power spectral parameterization, via specparam, in Jupyter Notebook and R Studio. We then apply this algorithm to EEG data in childhood (N = 60; Mage = 9.97, SD = 0.95) to illustrate its utility for developmental cognitive neuroscientists. Ultimately, the explicit parameterization of EEG power spectra may help us refine our understanding of how dynamic neural communication contributes to normative and aberrant cognition across the lifespan. Data and annotated analysis code for this manuscript are available on GitHub as a supplement to the open-access specparam toolbox.

Psychometric properties of infant electroencephalography: Developmental stability, reliability, and construct validity of frontal alpha asymmetry and delta-beta coupling.

Resting-state electroencephalography (EEG) provides developmental neuroscientists a noninvasive view into the neural underpinnings of cognition and emotion. Recently, the psychometric properties of two widely used neural measures in early childhood-frontal alpha asymmetry and delta-beta coupling-have come under scrutiny. Despite their growing use, additional work examining how the psychometric properties of these neural signatures may change across infancy is needed. The current study examined the developmental stability, split-half reliability, and construct validity of infant frontal alpha asymmetry and delta-beta coupling. Infants provided resting-state EEG data at 8, 12, and 18 months of age (N = 213). Frontal alpha asymmetry and delta-beta coupling showed significant developmental change from 8 to 18 months. Reliability for alpha asymmetry, and alpha, delta, and beta power, individually, was generally good. In contrast, the reliability of delta-beta coupling scores was poor. Associations between frontal alpha asymmetry and approach tendencies generally emerged, whereas stronger (over-coupled) delta-beta coupling scores were associated with profiles of dysregulation and low inhibition. However, the individual associations varied across time and specific measures of interest. We discuss these findings with a developmental lens, highlighting the importance of repeated measures to better understand links between neural signatures and typical and atypical development.

The centrality of temperament to the research domain criteria (RDoC): The earliest building blocks of psychopathology.

The research domain criteria (RDoC) is an innovative approach designed to explore dimensions of human behavior. The aim of this approach is to move beyond the limits of psychiatric categories in the hope of aligning the identification of psychological health and dysfunction with clinical neuroscience. Despite its contributions to adult psychopathology research, RDoC undervalues ontogenetic development, which circumscribes our understanding of the etiologies, trajectories, and maintaining mechanisms of psychopathology risk. In this paper, we argue that integrating temperament research into the RDoC framework will advance our understanding of the mechanistic origins of psychopathology beginning in infancy. In illustrating this approach, we propose the incorporation of core principles of temperament theories into a new "life span considerations" subsection as one option for infusing development into the RDoC matrix. In doing so, researchers and clinicians may ultimately have the tools necessary to support emotional development and reduce a young child's likelihood of psychological dysfunction beginning in the first years of life.

Maternal mindfulness during pregnancy predicts newborn neurobehavior.

Newborn neurobehavioral competencies portend a young child's abilities to modulate their arousal and attention in response to dynamic environmental cues. Although evidence suggests prenatal contributions to newborn neurobehavioral differences, no study to date has examined wellness-promoting traits, such as a pregnant woman's mindfulness, in this association. We examined whether a mother's mindfulness while pregnant related to neurobehavioral outcomes in her neonate, as well as whether maternal mindfulness moderated the link between prenatal maternal emotion dysregulation and newborn neurobehavior. Mothers (N = 162) reported on their mindfulness and emotion dysregulation while pregnant. Newborn arousal and attention were assessed at least 24 h after birth (M = 3.8 days, SD = 8.3) using the NICU Network Neurobehavioral Scale (NNNS). Highly mindful pregnant women reported lower levels of emotion dysregulation. Newborns of highly mindful mothers exhibited higher levels of arousal (e.g., excitability, motor activity) but did not differ in regards to attention at birth. Maternal emotion dysregulation while pregnant was associated with blunted newborn attention, but only among mothers who were less mindful. Our findings suggest that a mother's mindfulness while pregnant may influence her fetus' neurobehavioral development in ways that are evident at birth.

Prenatal maternal transdiagnostic, RDoC-informed predictors of newborn neurobehavior: Differences by sex.

We examined whether Research Domain Criteria (RDoC)-informed measures of prenatal stress predicted newborn neurobehavior and whether these effects differed by newborn sex. Multilevel, prenatal markers of prenatal stress were obtained from 162 pregnant women. Markers of the Negative Valence System included physiological functioning (respiratory sinus arrhythmia [RSA] and electrodermal [EDA] reactivity to a speech task, hair cortisol), self-reported stress (state anxiety, pregnancy-specific anxiety, daily stress, childhood trauma, economic hardship, and family resources), and interviewer-rated stress (episodic stress, chronic stress). Markers of the Arousal/Regulatory System included physiological functioning (baseline RSA, RSA, and EDA responses to infant cries) and self-reported affect intensity, urgency, emotion regulation strategies, and dispositional mindfulness. Newborns' arousal and attention were assessed via the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Path analyses showed that high maternal episodic and daily stress, low economic hardship, few emotion regulation strategies, and high baseline RSA predicted female newborns' low attention; maternal mindfulness predicted female newborns' high arousal. As for male newborns, high episodic stress predicted low arousal, and high pregnancy-specific anxiety predicted high attention. Findings suggest that RDoC-informed markers of prenatal stress could aid detection of variance in newborn neurobehavioral outcomes within hours after birth. Implications for intergenerational transmission of risk for psychopathology are discussed.

Behavioral and cognitive correlates of the aperiodic (1/f-like) exponent of the EEG power spectrum in adolescents with and without ADHD.

Efficient information processing facilitates cognition and may be disrupted in a number of neurodevelopmental conditions. And yet, the role of inefficient information processing and its neural underpinnings remains poorly understood. In the current study, we examined the cognitive and behavioral correlates of the aperiodic exponent of the electroencephalogram (EEG) power spectrum, a putative marker of disrupted, inefficient neural communication, in a sample of adolescents with and without ADHD (n = 184 nADHD = 87; Mage = 13.95 years, SD = 1.36). Exponents were calculated via FOOOF (Donoghue et al., 2020a) from EEG data recorded during an 8-minute baseline episode. Reaction time speed and variability, as well as drift diffusion parameters (including the drift rate parameter, a cognitive parameter directly related to inefficient information processing) were calculated. Adolescents with ADHD had smaller aperiodic exponents (a "flattened" EEG power spectrum) relative to their typically-developing peers. After controlling for ADHD, aperiodic exponents were related to reaction time variability and the drift rate parameter, but not in the expected direction. Our findings lend support for the aperiodic exponent as a neural correlate of disrupted information processing, and provide insight into the role of cortical excitation/inhibition imbalance in the pathophysiology of ADHD.

Prenatal substance exposure and maternal hostility from pregnancy to toddlerhood: Associations with temperament profiles at 16 months of age.

We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N = 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.

Prenatal maternal hair cortisol concentrations are related to maternal prenatal emotion dysregulation but not neurodevelopmental or birth outcomes.

Hair cortisol concentrations measured during pregnancy have emerged as a novel biomarker for prenatal stress exposure. However, associations between prenatal stress and distress, broadly defined, and hair cortisol concentrations during pregnancy are inconsistent. We examined relations among hair cortisol concentrations during the third trimester with (a) emotion dysregulation and (b) detailed measures of maternal prenatal stress. We also examined the predictive validity of maternal hair cortisol during pregnancy for adverse newborn health outcomes. Cortisol concentrations were derived from 6 cm of hair during the third trimester of pregnancy. Mothers reported on their emotion dysregulation and stress at this time. A standardized newborn neurobehavioral exam was conducted shortly after birth and newborn birth weight and gestational age were assessed from medical records. All hypotheses were preregistered on the Open Science Framework (osf.io/279ng). High levels of emotion dysregulation, but not stress, were predictive of high hair cortisol concentrations. Maternal prenatal BMI mediated the relation between maternal prenatal emotion dysregulation and hair cortisol concentrations. There was no association between hair cortisol and infant birth outcomes. This research supports the notion that transdiagnostic markers of psychopathology are important correlates of hair cortisol concentrations during pregnancy.

DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex.

Caregivers play a critical role in scaffolding infant stress reactivity and regulation, but the mechanisms by which this scaffolding occurs is unclear. Animal models strongly suggest that epigenetic processes, such as DNA methylation, are sensitive to caregiving behaviors and, in turn, offspring stress reactivity. We examined the direct effects of caregiving behaviors on DNA methylation in infants and infant stress reactivity. Infants and mothers (N = 128) were assessed during a free play when infants were 5 months old. Maternal responsiveness and appropriate touch were coded. and infant buccal epithelial cells were sampled to assess for DNA methylation of the glucocorticoid receptor gene, NR3c1 exon 1F. Infant cortisol reactivity was assessed in response to the still-face paradigm. Greater levels of maternal responsiveness and appropriate touch were related to less DNA methylation of specific regions in NR3c1 exon 1F, but only for females. There was no association with maternal responsiveness and appropriate touch or DNA methylation of NR3c1 exon 1F on prestress cortisol or cortisol reactivity. Our results are discussed in relation to programming models that implicate maternal care as an important factor in programing infant stress reactivity.

Los cuidadores juegan un papel esencial en el andamiaje de la reactividad y regulación del estrés infantil pero los mecanismos por medio de los cuales aparece este andamiaje no están claros. Los modelos animales fuertemente sugieren que los procesos epigenéticos, tales como la metilación del ADN, son sensibles a los comportamientos de prestaciones de cuidado y por consiguiente a la reactividad al estrés por parte de los hijos. Examinamos los efectos directos que los comportamientos de prestaciones de cuidado tienen sobre la metilación de ADN en infantes y, por consiguiente, la reactividad del estrés infantil. Los infantes y sus madres (N = 128) fueron evaluados durante una sesión de juego libre cuando los infantes tenían 5 meses de edad. Se codificó la sensibilidad materna y la apropiada forma de tocar y se obtuvo muestra de las células epiteliales bucales del infante para analizar la metilación de ADN del gen receptor glucocorticoide, NR3c1, exón 1F. Se evaluó la reactividad del infante al cortisol como respuesta al paradigma de la cara quieta. Niveles mayores de sensibilidad materna y apropiada forma de tocar se relacionaron con menos metilación de ADN de regiones específicas en NR3c1 exón 1F, aunque sólo en las niñas. No se presentó ninguna asociación con la sensibilidad materna y la apropiada forma de tocar, o metilación de ADN de NR3c1 exón 1F en el cortisol pre-estrés o la reactividad del cortisol. Nuestros resultados se discuten en relación con modelos de programación que implican cuidado materno como un importante factor en la programación de la reactividad del estrés del infante.

Les personnes prenant soin des enfants jouent un rôle critique dans l'échafaudage de la réaction au stress du nourrisson et la régulation mais les mécanismes selon lesquels cet échafaudage se bâtit ne sont pas clairs. Les modèles animaux suggèrent fortement que des processus épigénétiques, comme la méthylation de l'ADN, sont sensibles au comportements de qui prend soin d'eux et en conséquence déclenchent un réaction au stress. Nous avons examiné les effets directs des comportements soignants sur la méthylation de l'ADN chez les bébés, en ensuite sur la réaction au stress du nourrisson. Des nourrissons et leurs mères (N = 128) ont été évalués au moyen d'un jeu libre quand les bébés avaient 5 mois d'âge. La réaction maternelle et le toucher approprié ont été codés et des cellules épithéliales buccales du bébé ont été prélevées afin d'évaluer la méthylation de l'ADN du gène récepteur glucocorticoïde, le NR3c1 exon 1F. La réaction du cortisol du bébé a été évaluée en réponse au paradigme du visage immuable. Des niveaux plus élevés de réaction maternelle et de toucher approprié étaient liés à une méthylation de l'ADN des régions spécifiques de NR3c1 exon 1F moindre, mais seulement chez les filles. On n'a trouvé aucun lien avec la réaction maternelle et le toucher approprié ou de méthylation NR3c1 exon 1F de l'ADN sur le cortisol pré-test ou de réaction du cortisol. Nos résultats sont discutés en relation aux modèles de programme qui impliquent que le soin maternel en tant que facteur important dans la programmation de la réaction au stress du bébé.

Intergenerational transmission of emotion dysregulation: Part II. Developmental origins of newborn neurobehavior.

We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors-arousal and attention-via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.

Testing the programming of temperament and psychopathology in two independent samples of children with prenatal substance exposure.

Prenatal programming models have rarely been applied to research on children with prenatal substance exposure, despite evidence suggesting that prenatal drug exposure is a form of stress that impacts neurodevelopmental outcomes and risk for psychopathology. Utilizing data from two longitudinal multisite studies comprising children prenatally exposed to substances as well as a nonexposed comparison group (Maternal Lifestyle Study, n = 1,388; Infant Development, Environment, and Lifestyle study, n = 412), we tested whether early phenotypic indicators of hypothesized programming effects, indexed by growth parameters at birth and infant temperament, served as a link between prenatal substance exposure and internalizing and externalizing behavior at age 5. Latent profile analysis indicated that individual differences in reactivity and regulation for infants prenatally exposed to substances was best characterized by four temperament profiles. These profiles were virtually identical across two independent samples, and demonstrated unique associations with adjustment difficulties nearly 5 years later. Results of path analysis using structural equation modeling also showed that increased prenatal substance exposure was linked to poorer growth parameters at birth, profiles of temperamental reactivity in infancy, and internalizing and externalizing behavior at age 5. This pathway was partially replicated across samples. This study was among the first to link known individual-level correlates of prenatal substance exposure into a specific pathway to childhood problem behavior. Implications for the developmental origins of a child's susceptibility to psychopathology as a result of intrauterine substance exposure are discussed.

Association between early life adversity and inflammation during infancy.

Early life adversity is associated with adult elevations of inflammatory markers such as circulating levels of C-reactive protein (CRP). Few studies have measured inflammation or its association with psychosocial stress during infancy. Existing evidence suggests that early adversity can embed itself into young children's biology with implications for lifelong development. This study examined the association between psychosocial stress and salivary CRP in infants. Early adversity in the form of socioeconomic disadvantage and maternal psychosocial stress were measured when infants were 17 months old. Resting state saliva samples were collected to assess CRP (pg/ml) levels via enzyme immunoassay. Results revealed that both socioeconomic disadvantage and maternal psychosocial stress were independently associated with higher infant CRP levels. These results raise questions about timing of exposure to adversity, and about the potentially lasting effects on inflammatory processes when such exposure occurs early in development.

Shaping emotion regulation: attunement, symptomatology, and stress recovery within mother-infant dyads.

The foundations of emotion regulation are organized, in part, through repeated interactions with one's caregiver in infancy. Less is known about how stress physiology covaries between a mother and her infant within these interactions, leaving a gap in our understanding of how the biological basis of emotion regulation develops. This study investigated physiological attunement between mothers and their 5-month-old infants, as well as the influence of maternal depression and anxiety, during stress recovery. During the reengagement phase of the Still Face Paradigm, mother-infant dyads exhibited negative attunement, as measured by inverse covariation of respiratory sinus arrhythmia (RSA). Increases in maternal RSA corresponded to decreases in infant RSA, underscoring dyadic adjustment during recovery. Moreover, infant regulation differed as a function of maternal anxiety, with more anxious mothers having infants with higher RSA during reengagement. Implications for the consolidation of regulatory capabilities within the context of the early caregiving relationship are discussed.

Prenatal Stress, Fearfulness, and the Epigenome: Exploratory Analysis of Sex Differences in DNA Methylation of the Glucocorticoid Receptor Gene.

Exposure to stress in utero is a risk factor for the development of problem behavior in the offspring, though precise pathways are unknown. We examined whether DNA methylation of the glucocorticoid receptor gene, NR3C1, was associated with experiences of stress by an expectant mother and fearfulness in her infant. Mothers reported on prenatal stress and infant temperament when infants were 5 months old (n = 68). Buccal cells for methylation analysis were collected from each infant. Prenatal stress was not related to infant fearfulness or NR3C1 methylation in the sample as a whole. Exploratory sex-specific analysis revealed a trend-level association between prenatal stress and increased methylation of NR3C1 exon 1F for female, but not male, infants. In addition, increased methylation was significantly associated with greater fearfulness for females. Results suggest an experience-dependent pathway to fearfulness for female infants via epigenetic modification of the glucocorticoid receptor gene. Future studies should examine prenatal stress in a comprehensive fashion while considering sex differences in epigenetic processes underlying infant temperament.