Developmental coupling of brain iron and intrinsic activity in infants during the first 150 days.

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron.

Fetal Frontolimbic Connectivity Prospectively Associates With Aggression in Toddlers.

Background: Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding regarding the etiology of aggression. The present study leveraged fetal resting-state functional magnetic resonance imaging to identify candidate neurocircuitry for the onset of aggressive behaviors before symptom emergence. Methods: Pregnant mothers were recruited during the third trimester of pregnancy to complete a fetal resting-state functional magnetic resonance imaging scan. Mothers subsequently completed the Child Behavior Checklist to assess child aggression at 3 years postpartum (n = 79). Independent component analysis was used to define frontal and limbic regions of interest. Results: Child aggression was not related to within-network connectivity of subcortical limbic regions or within-medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic functional connectivity and toddler internalizing symptoms. Conclusions: Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptoms. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.

Effects of prenatal psychosocial stress and COVID-19 infection on infant attention and socioemotional development.

BACKGROUND: The COVID-19 pandemic dramatically altered the psychosocial environment of pregnant women and new mothers. In addition, prenatal infection is a known risk factor for altered fetal development. Here we examine joint effects of maternal psychosocial stress and COVID-19 infection during pregnancy on infant attention at 6 months postpartum. METHOD: One-hundred and sixty-seven pregnant mothers and infants (40% non-White; n = 71 females) were recruited in New York City (n = 50 COVID+, n = 117 COVID-). Infants' attentional processing was assessed at 6 months, and socioemotional function and neurodevelopmental risk were evaluated at 12 months. RESULTS: Maternal psychosocial stress and COVID-19 infection during pregnancy jointly predicted infant attention at 6 months. In mothers reporting positive COVID-19 infection, higher prenatal psychosocial stress was associated with lower infant attention at 6 months. Exploratory analyses indicated that infant attention in turn predicted socioemotional function and neurodevelopmental risk at 12 months. CONCLUSIONS: These data suggest that maternal psychosocial stress and COVID-19 infection during pregnancy may have joint effects on infant attention at 6 months. This work adds to a growing literature on the effects of the COVID-19 pandemic on infant development, and may point to maternal psychosocial stress as an important target for intervention. IMPACT: This study found that elevated maternal psychosocial stress and COVID-19 infection during pregnancy jointly predicted lower infant attention scores at 6 months, which is a known marker of risk for neurodevelopmental disorder. In turn, infant attention predicted socioemotional function and risk for neurodevelopmental disorder at 12 months. These data suggest that maternal psychosocial stress may modulate the effects of gestational infection on neurodevelopment and highlight malleable targets for intervention.

Intergenerational Transmission of Maternal Childhood Maltreatment Prior to Birth: Effects on Human Fetal Amygdala Functional Connectivity.

OBJECTIVE: Childhood maltreatment (CM) is a potent risk factor for developing psychopathology later in life. Accumulating research suggests that the influence is not limited to the exposed individual but may also be transmitted across generations. In this study, we examine the effect of CM in pregnant women on fetal amygdala-cortical function, prior to postnatal influences. METHOD: Healthy pregnant women (N = 89) completed fetal resting-state functional magnetic resonance imaging (rsfMRI) scans between the late second trimester and birth. Women were primarily from low socioeconomic status households with relatively high CM. Mothers completed questionnaires prospectively evaluating prenatal psychosocial health and retrospectively evaluating trauma from their own childhood. Voxelwise functional connectivity was calculated from bilateral amygdala masks. RESULTS: Connectivity of the amygdala network was relatively higher to left frontal areas (prefrontal cortex and premotor) and relatively lower to right premotor area and brainstem areas in fetuses of mothers exposed to higher CM. These associations persisted after controlling for maternal socioeconomic status, maternal prenatal distress, measures of fetal motion, and gestational age at the time of scan and at birth. CONCLUSION: Pregnant women's experiences of CM are associated with offspring brain development in utero. The strongest effects were found in the left hemisphere, potentially indicating lateralization of the effects of maternal CM on the fetal brain. This study suggests that the time frame of the Developmental Origins of Health and Disease research should be extended to exposures from mothers' childhood, and indicates that the intergenerational transmission of trauma may occur prior to birth.

Fetal behavior during MRI changes with age and relates to network dynamics.

Fetal motor behavior is an important clinical indicator of healthy development. However, our understanding of associations between fetal behavior and fetal brain development is limited. To fill this gap, this study introduced an approach to automatically and objectively classify long durations of fetal movement from a continuous four-dimensional functional magnetic resonance imaging (fMRI) data set, and paired behavior features with brain activity indicated by the fMRI time series. Twelve-minute fMRI scans were conducted in 120 normal fetuses. Postnatal motor function was evaluated at 7 and 36 months age. Fetal motor behavior was quantified by calculating the frame-wise displacement (FD) of fetal brains extracted by a deep-learning model along the whole time series. Analyzing only low motion data, we characterized the recurring coactivation patterns (CAPs) of the supplementary motor area (SMA). Results showed reduced motor activity with advancing gestational age (GA), likely due in part to loss of space (r = -.51, p < .001). Evaluation of individual variation in motor movement revealed a negative association between movement and the occurrence of coactivations within the left parietotemporal network, controlling for age and sex (p = .003). Further, we found that the occurrence of coactivations between the SMA to posterior brain regions, including visual cortex, was prospectively associated with postnatal motor function at 7 months (r = .43, p = .03). This is the first study to pair fetal movement and fMRI, highlighting potential for comparisons of fetal behavior and neural network development to enhance our understanding of fetal brain organization.

Perceived medical care quality during COVID-19 illness links socioeconomic disadvantage to vaccine hesitancy.

Maximizing vaccine uptake is critical for the optimal implementation of COVID-19 immunization programs. Indicators of socioeconomic status (SES) have been associated with variations in COVID-19 vaccine uptake in the United States. The present study investigates COVID-19 vaccination behavior in individuals with history of COVID-19 infection, with the specific goal of understanding whether experiences during illness explain socioeconomic disproportionalities in vaccine uptake. We leveraged a large sample of adults (n = 1584) infected with COVID-19 in NYC to examine this question, investigating whether specific experiences during illness explained the association between socioeconomic status and COVID-19 vaccine hesitancy. Data from this study were collected during February and March 2021. Principal component analysis was used to create three composite variables that measure distinct COVID-19 related experiences: infection-related health impacts, pandemic-related psychosocial disruption, and perceived quality of medical care during COVID-19 illness. Neither infection-related impacts nor psychosocial disruption were related to vaccine hesitancy after adjusting for related sociodemographic covariates. However, perceptions of higher quality care received during COVID-19 illness predicted decreased COVID-19 vaccine hesitancy. Furthermore, mediation analysis revealed that perceived care quality during COVID-19 illness mediate the relationship between objective socioeconomic risk and COVID-19 vaccine hesitancy. These findings highlight patient-reported care quality during illness as a novel target that may increase vaccine uptake among socioeconomically vulnerable populations.

Empirical evaluation of human fetal fMRI preprocessing steps.

Increased study and methodological innovation have led to growth in the field of fetal brain fMRI. An important gap yet to be addressed is optimization of fetal fMRI preprocessing. Rapid developmental changes, imaged within the maternal compartment using an abdominal coil, introduce novel constraints that challenge established methods used in adult fMRI. This study evaluates the impact of (1) normalization to a group mean-age template versus normalization to an age-matched template; (2) independent components analysis (ICA) denoising at two criterion thresholds; and (3) smoothing using three kernel sizes. Data were collected from 121 fetuses (25-39 weeks, 43.8% female). Results indicate that the mean age template is superior in older fetuses, but less optimal in younger fetuses. ICA denoising at a more stringent threshold is superior to less stringent denoising. A larger smoothing kernel can enhance cross-hemisphere functional connectivity. Overall, this study provides improved understanding of the impact of specific steps on fetal image quality. Findings can be used to inform a common set of best practices for fetal fMRI preprocessing.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

Fetal Hippocampal Connectivity Shows Dissociable Associations with Maternal Cortisol and Self-Reported Distress during Pregnancy.

Maternal stress can shape long-term child neurodevelopment beginning in utero. One mechanism by which stress is transmitted from mothers to their offspring is via alterations in maternal cortisol, which can cross the placenta and bind to glucocorticoid receptor-rich regions in the fetal brain, such as the hippocampus. Although prior studies have demonstrated associations between maternal prenatal stress and cortisol levels with child brain development, we lack information about the extent to which these associations originate prior to birth and prior to confounding postnatal influences. Pregnant mothers (n = 77) completed questionnaires about current perceived stress, depressive symptoms, and anxiety symptoms, provided three to four salivary cortisol samples, and completed a fetal resting-state functional MRI scan during their second or third trimester of pregnancy (mean gestational age = 32.8 weeks). Voxelwise seed-based connectivity analyses revealed that higher prenatal self-reported distress and higher maternal cortisol levels corresponded to dissociable differences in fetal hippocampal functional connectivity. Specifically, self-reported distress was correlated with increased positive functional coupling between the hippocampus and right posterior parietal association cortex, while higher maternal cortisol was associated with stronger positive hippocampal coupling with the dorsal anterior cingulate cortex and left medial prefrontal cortex. Moreover, the association between maternal distress, but not maternal cortisol, on fetal hippocampal connectivity was moderated by fetal sex. These results suggest that prenatal stress and peripheral cortisol levels may shape fetal hippocampal development through unique mechanisms.

Perceived discrimination as a modifier of health, disease, and medicine: empirical data from the COVID-19 pandemic.

Increasing reports of long-term symptoms following COVID-19 infection, even among mild cases, necessitate systematic investigation into the prevalence and type of lasting illness. Notably, there is limited data regarding the influence of social determinants of health, like perceived discrimination and economic stress, that may exacerbate COVID-19 health risks. Here, 1,584 recovered COVID-19 patients that experienced mild to severe forms of disease provided detailed medical and psychosocial information. Path analyses examined hypothesized associations between discrimination, illness severity, and lasting symptoms. Secondary analyses evaluated sex differences, timing of infection, and impact of prior mental health problems. Post hoc logistic regressions tested social determinants hypothesized to predict neurological, cognitive, or mood symptoms. 70.6% of patients reported presence of one or more lasting symptom after recovery. 19.4% and 25.1% of patients reported lasting mood or cognitive/memory problems. Perceived discrimination predicted increased illness severity and increased lasting symptom count, even when adjusting for sociodemographic factors and mental/physical health comorbidities. This effect was specific to stress related to discrimination, not to general stress levels. Further, patient perceptions regarding quality of medical care influenced these relationships. Finally, illness early in the pandemic is associated with more severe illness and more frequent lasting complaints. Lasting symptoms after recovery from COVID-19 are highly prevalent and neural systems are significantly impacted. Importantly, psychosocial factors (perceived discrimination and perceived SES) can exacerbate individual health risk. This study provides actionable directions for improved health outcomes by establishing that sociodemographic risk and medical care influence near and long-ranging health outcomes. All data from this study have been made publicly available.

Prenatal distress links maternal early life adversity to infant stress functioning in the next generation.

Maternal stress in pregnancy exerts powerful programming effects into the next generation. Yet it remains unclear whether and how adversity from other times in the woman's life influences her prenatal stress and her offspring's stress functioning. In a sample of 217 Black American mother-infant dyads, we examined whether different types of maternal stress were differentially related to her infant's stress functioning within the first few months after birth. We prospectively assessed maternal distress (perceived stress, depression, and anxiety) early and late in pregnancy, infant behavioral adaption in the context of a mild stressor at 2 weeks of age, and infant diurnal cortisol at 3-6 months of age. We additionally collected retrospective reports of maternal experiences of lifetime discrimination and childhood adversity. Maternal distress experienced late, but not early, in pregnancy predicted lower infant attention in the context of a stressor. Moreover, lifetime experiences of discrimination indirectly impacted infant attention by increasing maternal distress late in pregnancy. These effects were specific to infant behavioral adaptation and were not related to infant diurnal cortisol levels. However, infant diurnal cortisol levels were associated with maternal experiences of discrimination from prior to pregnancy and adversity from the mother's childhood even after controlling for prenatal distress. Our results underscore the cascading nature of stress across the mother's life span and across generations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A survey of protocols from 54 infant and toddler neuroimaging research labs.

Infant and toddler MRI enables unprecedented insight into the developing brain. However, consensus about optimal data collection practices is lacking, which slows growth of the field and impedes replication efforts. The goal of this study was to collect systematic data across a large number of infant/toddler research laboratories to better understand preferred practices. Survey data addressed MRI acquisition strategies, scan success rates, visit preparations, scanning protocols, accommodations for families, study design, and policies regarding incidental findings. Respondents had on average 8 years' experience in early life neuroimaging and represented more than fifty research laboratories. Areas of consensus across labs included higher success rates among newborns compared to older infants or toddlers, high rates of data loss across age groups, endorsement of multiple layers of hearing protection, and age-specific scan preparation and participant accommodation. Researchers remain divided on decisions in longitudinal study design and practices regarding incidental findings. This study summarizes practices honed over years of work by a large collection of scientists, which may serve as an important resource for those new to the field. The ability to reference data about best practices facilitates future harmonization, data sharing, and reproducibility, all of which advance this important frontier in developmental science.

COVID-19 patient accounts of illness severity, treatments and lasting symptoms.

First-person accounts of COVID-19 illness and treatment can complement and enrich data derived from electronic medical or public health records. With patient-reported data, it is uniquely possible to ascertain in-depth contextual information as well as behavioral and emotional responses to illness. The Novel Coronavirus Illness Patient Report (NCIPR) dataset includes complete survey responses from 1,584 confirmed COVID-19 patients ages 18 to 98. NCIPR survey questions address symptoms, medical complications, home and hospital treatments, lasting effects, anxiety about illness, employment impacts, quarantine behaviors, vaccine-related behaviors and effects, and illness of other family/household members. Additional questions address financial security, perceived discrimination, pandemic impacts (relationship, social, stress, sleep), health history, and coping strategies. Detailed patient reports of illness, environment, and psychosocial impact, proximal to timing of infection and considerate of demographic variation, is meaningful for understanding pandemic-related public health from the perspective of those that contracted the disease.

Behavioral coping phenotypes and associated psychosocial outcomes of pregnant and postpartum women during the COVID-19 pandemic.

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Neonatal neurobehavior in infants with autism spectrum disorder.

AIM: To investigate neurobehavioral maturation for neonates who are later diagnosed with autism spectrum disorder (ASD). METHOD: In a prospective longitudinal design, neonatal neurobehavior was examined monthly in 1- to 3-month-old infants at elevated and low familial likelihood of ASD (n=60). At 2 years, infants were seen for a clinical best-estimate evaluation, resulting in 18 infants with ASD and 36 typically developing infants. Repeated-measures analysis of variance models were conducted to examine the effects of age, diagnostic group, and their interactions. RESULTS: Neurobehavioral maturation of infants diagnosed with ASD was largely comparable to typically developing infants from 1 to 3 months, with the exception of the development of attention. Object-focused attention was significantly attenuated for infants with ASD beginning at 2 to 3 months and was predictive of social-communication skills 2 years later. INTERPRETATION: This is the first study to prospectively examine neonatal neurobehavior of infants at an elevated familial likelihood of ASD who later received a diagnosis. Despite relatively intact neurological and behavioral maturation in the neonatal period, attention to objects emerged as a key early indicator of ASD. This suggests a complex attentional vulnerability within the first 3 months of life that may be associated with cascading sequelae of social-communication challenges and the emergence of ASD.

Changes in social support of pregnant and postnatal mothers during the COVID-19 pandemic.

OBJECTIVE: Our objectives were to assess in perinatal women: the most effective methods used to meet social support needs during COVID-19, the impact of COVID-19 on self-reported social support levels, and how perceived change in social support related to distress, depression, and mental health. DESIGN: One-time survey administered from April to August 2020 SETTING: Online PARTICIPANTS: Pregnant and postpartum women with infants less than 6 months of age MEASUREMENT AND FINDINGS: Participants indicated the methods they used to meet social support needs during COVID-19. They self-rated their social support level pre- and during pandemic and their distress, depressive symptoms, and mental health changes on a Likert scale. Out of 1142 participants, the most effective methods for obtaining social support during the pandemic were virtual means (e.g. video call) and interaction with friends. There was a significant difference in distribution of self-reported levels of social support before and during the pandemic, with more respondents reporting a decrease in support. Decreases in social support were associated with higher distress levels, higher levels of depressive symptoms, and poorer mental health. KEY CONCLUSIONS: Perinatal women reported decreased social support during the COVID-19 pandemic which was associated with poorer mental health. Using virtual means of social support and support provided by friends had the largest positive effect on perceived social support levels. IMPLICATIONS FOR PRACTICE: Interventions using virtual support means from friends may be helpful to improve social support and mental health in this population.

Social determinants of health exacerbate disparities in COVID-19 illness severity and lasting symptom complaints.

BACKGROUND: Increasing reports of long-term symptoms following COVID-19 infection, even among mild cases, necessitates systematic investigation into the prevalence and type of lasting illness. Notably, there is limited data regarding the influence of social determinants of health, like perceived discrimination and economic stress, which may exacerbate COVID-19 health risks. The primary goals of this study are to test the bearing of subjective experiences of discrimination, financial security, and quality of care on illness severity and lasting symptom complaints. METHODS: 1,584 recovered COVID-19 patients that experienced mild to severe forms of the disease provided information about their illness, medical history, lasting symptoms, and psychosocial information. Prevalence data isolated differences in patients infected early versus late in the pandemic. Path analyses examined hypothesized associations between discrimination, illness severity, and lasting symptoms. Post hoc logistic regressions tested social determinants hypothesized to predict neurological, cognitive, or mood symptoms. RESULTS: 70.6% of patients reported presence of one or more lasting symptoms after recovery. Neural systems were especially impacted, and 19.4% and 25.1% of patients reported mood or cognitive/memory complaints, respectively. Path models demonstrated that frequency and stress about experiences of discrimination predicted increased illness severity and increased lasting symptom count, even when adjusting for sociodemographic factors and mental/physical health comorbidities. Notably, this effect was specific to stress related to discrimination, and did not extend to general stress levels. Further, perceived but not objective socioeconomic status (SES) was associated with increased lasting symptom complaints after recovery. Finally, associations between discrimination and illness differed with individual perceptions about quality of medical care. CONCLUSIONS: Lasting symptoms after recovery from COVID-19 are highly prevalent and neural systems are significantly impacted. Importantly, psychosocial factors (perceived discrimination and perceived SES) can exacerbate individual health risk. This study provides actionable directions for improved health outcomes by establishing that sociodemographic risk and medical care influence near and long-ranging health outcomes.

COVID-19 patient accounts of illness severity, treatments and lasting symptoms.

First-person accounts of COVID-19 illness and treatment complement and enrich data derived from electronic medical or public health records. With patient-reported data, it is uniquely possible to ascertain in-depth contextual information as well as behavioral and emotional responses to illness. The Novel Coronavirus Illness Patient Report (NCIPR) dataset includes complete survey responses from 1,592 confirmed COVID-19 patients ages 18 to 98. NCIPR survey questions address symptoms, medical complications, home and hospital treatments, lasting effects, anxiety about illness, employment impacts, quarantine behaviors, vaccine-related behaviors and effects, and illness of other family/household members. Additional questions address financial security, perceived discrimination, pandemic impacts (relationship, social, stress, sleep), health history, and coping strategies. Detailed patient reports of illness, environment, and psychosocial impact, proximal to timing of infection and considerate of demographic variation, is meaningful for understanding pandemic-related public health from the perspective of those that contracted the disease.

Maternal Childhood Adversity Associates With Frontoamygdala Connectivity in Neonates.

BACKGROUND: It is well established that exposure to adversity, especially during sensitive periods of development such as childhood, has both behavioral (e.g., increasing one's risk for psychiatric illnesses) and neurobiological consequences. But could these effects of early-life exposure to adversity also be transmitted across generations? We directly address this question, investigating the associations between maternal exposure to adversity during her own childhood and neural connectivity in her neonate. METHODS: Mothers from a sample of Black mother-neonate dyads (n = 48)-a group that is disproportionately affected by early-life adversity-completed questionnaires assessing their current distress (i.e., a composite measure of anxiety, depression, and perceived stress) during the first and third trimesters of pregnancy and retrospectively reported on their own childhood experiences of abuse and neglect. At 1 month postpartum, neonatal offspring of these women underwent a resting-state functional magnetic resonance imaging scan during natural sleep. RESULTS: Greater maternal exposure to emotional neglect during her own childhood correlated with stronger functional connectivity of two different frontoamygdala circuits in these neonates, as early as 1 month after birth. This effect was specific to early experiences of emotional neglect and was not explained by maternal exposure to other forms of childhood maltreatment or by maternal distress during pregnancy. CONCLUSIONS: These results provide novel evidence that the absence of emotional support early in a mother's life, years before conception, are associated with neural changes-namely, in functional connectivity between the amygdala and medial prefrontal regions-in her offspring shortly after birth.