Faculty Bibliography

Large-scale functional connectome formation and re-organization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated prior to birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function.SIGNIFICANCE STATEMENTThe fetal to neonatal period is well known as a critical stage in brain development. Rapid neurodevelopmental processes establish key functional neural circuits of the human brain. Prenatal risk factors may interfere with early trajectories of connectome formation and thereby shape future health outcomes. Recent advances in MRI have made it possible to examine fetal brain functional connectivity. In this study, we evaluate the network topography of normative functional network development during connectome genesis in utero Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.

This study describes maternal and infant contributions to dyadic affective exchanges during the Still-Face Paradigm (SFP) in an understudied mostly low-income sample. One hundred eleven mothers and their 7-month-old infants were videotaped during the SFP to analyze how a social stressor affects mother-infant positive and negative affective exchanges during interaction. The SFP includes 3 episodes: baseline, maternal still-face, and reunion. Maternal and infant positive and negative affect were scored by masked reliable coders. Data were analyzed using the Actor-Partner Interdependence Model to test the hypotheses that each partner's affectivity during the baseline episode would predict their own affectivity during the reunion episode (actor effects). We also expected that each partner's affectivity during the baseline episode would influence the other partner's affectivity during the reunion episodes (partner effects). After controlling for infant sex and maternal education, results provided evidence for actor effects for maternal and infant positive affect, and for partner effects for maternal baseline positive affect to infant positive affect during the reunion. One significant partner effect was observed for negative affect: Infant negativity during baseline predicted greater maternal negativity during reunion. Findings confirm that both mothers and infants contribute to dyadic affective processes during the SFP but specific findings vary depending on the affective valence in question. Clinical implications and future research are discussed.

Background and aims.- Prevalence of psychiatric disorders differs in males and females, and neurological studies suggest that sex-linked variation in the brain may underlie this dissociation. However, the origin of this difference, and how early in human life sexual dimorphism in brain function emerges is a topic that requires further investigation. Here, we address this gap by assessing brain resting-state functional connectivity (RSFC) between and within brain networks as it relates to fetal sex and gestational age (GA). Methods.- We examined 118 typical human fetuses (70 male; 48 female) between 25.9 and 39.6 weeks GA. Infomap was used to derive 16 separable fetal neural networks distributed across cortical, subcortical, and cerebellar regions. Using enrichment analysis, we identified network pairs revealing distinct patterns of GArelated change in males and females. Results.- Sex-dependent variation of between- and within- network RSFC-GA associations was observed: while females exhibited GA-related variation in connectivity between posterior cingulate and temporal pole regions, and between pre-frontal and cerebellar regions, males demonstrated increased intracerebellar RSFC with advancing age. Conclusions.- Such observations confirm that sex-related differences in functional brain development are present before birth. An important next step in this line of research will be to follow children across early development and discover how sex-related variation in network development relates to future health outcomes

Lead represents a highly prevalent metal toxicant with potential to alter human biology in lasting ways. A population segment that is particularly vulnerable to the negative consequences of lead exposure is the human fetus, as exposure events occurring before birth are linked to varied and long-ranging negative health and behavioral outcomes. An area that has yet to be addressed is the potential that lead exposure during pregnancy alters brain development even before an individual is born. Here, we combine prenatal lead exposure information extracted from newborn bloodspots with the human fetal brain functional MRI data to assess whether neural network connectivity differs between lead-exposed and lead-naïve fetuses. We found that neural connectivity patterns differed in lead-exposed and comparison groups such that fetuses that were not exposed demonstrated stronger age-related increases in cross-hemispheric connectivity, while the lead-exposed group demonstrated stronger age-related increases in posterior cingulate cortex (PCC) to lateral prefrontal cortex (PFC) connectivity. These are the first results to demonstrate metal toxicant-related alterations in human fetal neural connectivity. Remarkably, the findings point to alterations in systems that support higher-order cognitive and regulatory functions. Objectives for future work are to replicate these results in larger samples and to test the possibility that these alterations may account for significant variation in future child cognitive and behavioral outcomes.

Despite prior extensive investigations of the interactions between the amygdala and prefrontal cortex, few studies have simultaneously considered activation and structural connectivity in this circuit, particularly as it pertains to adolescent socioemotional development. The current multi-modal study delineated the correspondence between uncinate fasciculus (UF) connectivity and amygdala habituation in a large adolescent sample that was drawn from a population-based sample. We then examined the influence of demographic variables (age, gender, and pubertal status) on the relation between UF connectivity and amygdala habituation. 106 participants (15-17 years) completed DTI and an fMRI emotional face processing task. Left UF fractional anisotropy was associated with left amygdala habituation to fearful faces, suggesting that increased structural connectivity of the UF may facilitate amygdala regulation. Pubertal status moderated this structure-function relation, such that the association was stronger in those who were less mature. Therefore, UF connectivity may be particularly important for emotion regulation during early puberty. This study is the first to link structural and functional limbic circuitry in a large adolescent sample with substantial representation of ethnic minority participants, providing a more comprehensive understanding of socioemotional development in an understudied population.

Non-heme iron is a vital metabolic cofactor for many core processes of brain development including myelination, dendritogenesis, and neurotransmitter synthesis, and accumulates in the brain with age. However, little is known about development-related differences in brain iron and its association with emerging cognitive abilities during formative years. In this study, we estimated brain iron via R2* relaxometry in children ages 7-16 (N = 57; 38 females) and examined its relation to age-related differences in cognitive ability. As we hypothesized, age correlated positively with iron content in the hippocampus and across subregions of the basal ganglia. The magnitude of age differences in iron content differed between regions such that the largest effects were observed in basal ganglia subregions: globus pallidus, substantia nigra, caudate nucleus, and putamen, as compared to values obtained for the hippocampus and red nucleus. We did not observe sex or hemispheric differences in iron content. Notably, greater brain iron content was associated with both faster processing speed and higher general intelligence, and shared 21.4% of the age-related improvement in processing speed and 12.5% of the improvement in general intelligence. These results suggest that non-heme iron plays a central neurobiological role in the development of critical cognitive abilities during childhood.

Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.

Healthy parenting may be protective against the development of emotional psychopathology, particularly for children reared in stressful environments. Little is known, however, about the brain and behavioral mechanisms underlying this association, particularly during childhood and adolescence, when emotional disorders frequently emerge. Here, we demonstrate that psychological control, a parenting strategy known to limit socioemotional development in children, is associated with altered brain and behavioral responses to emotional conflict in 27 at-risk (urban, lower income) youth, ages 9-16. In particular, youth reporting higher parental psychological control demonstrated lower activity in the left anterior insula, a brain area involved in emotion conflict processing, and submitted faster but less accurate behavioral responses-possibly reflecting an avoidant pattern. Effects were not replicated for parental care, and did not generalize to an analogous nonemotional conflict task. We also find evidence that behavioral responses to emotional conflict bridge the previously reported link between parental overcontrol and anxiety in children. Effects of psychological control may reflect a parenting style that limits opportunities to practice self-regulation when faced with emotionally charged situations. Results support the notion that parenting strategies that facilitate appropriate amounts of socioemotional competence and autonomy in children may be protective against social and emotional difficulties.

Socioeconomic disadvantage (SED) experienced in early life is linked to a range of risk behaviors and diseases. Neuroimaging research indicates that this association is mediated by functional changes in corticostriatal reward systems that modulate goal-directed behavior, reward evaluation, and affective processing. Existing research has focused largely on adults and within-household measures as an index of SED, despite evidence that broader community-level SED (e.g., neighborhood poverty levels) has significant and sometimes distinct effects on development and health outcomes. Here, we test effects of both household- and community-level SED on resting-state functional connectivity (rsFC) of the ventral striatum (VS) in 100 racially and economically diverse children and adolescents (ages 6-17). We observed unique effects of household income and community SED on VS circuitry such that higher community SED was associated with reduced rsFC between the VS and an anterior region of the medial prefrontal cortex (mPFC), whereas lower household income was associated with increased rsFC between the VS and the cerebellum, inferior temporal lobe, and lateral prefrontal cortex. Lower VS-mPFC rsFC was also associated with higher self-reported anxiety symptomology, and rsFC mediated the link between community SED and anxiety. These results indicate unique effects of community-level SED on corticostriatal reward circuitry that can be detected in early life, which carries implications for future interventions and targeted therapies. In addition, our findings raise intriguing questions about the distinct pathways through which specific sources of SED can affect brain and emotional development.