The capacity to engage in purposeful, goal-directed behaviors, known as executive functioning (EF), provides a foundation for mental health, and academic and social functioning. EF is therefore a target for early intervention services aimed at reducing risk for psychopathology and school difficulties. However, targeted intervention efforts are limited by the difficulty of assessing EF prior to age 2. Resting state functional connectivity MRI (rs-fcMRI) allows for assessment of brain systems implicated in EF beginning in the neonatal period. Advanced computational methods applied with rs-fcMRI have shed light on the organization of the brain into dissociable functional networks that support high level cognitive processes, such as EF. The current proposal seeks to apply these methods to examine functional brain networks during infancy as predictors of emerging EF skills at 2 years of age, when reliable behavioral assessment becomes possible. In addition to increasing understanding of the neurodevelopmental processes preceding observable EF skills, examining these brain networks has potential to elucidate early environmental influences on EF. Associations between prenatal stress and difficulties with EF in childhood are thought to be explained by altered trajectories of brain development. However, hypothesized connections between prenatal stress, early brain development and emerging EF skills have not been tested. Under the current proposal, the applicant will test these connections in a unique longitudinal data set that includes extensive characterization of the pre- and postnatal environment, infant rs-fcMRI scans at 2 weeks and 1 year of age, and EF assessment at 2 years. She will employ advanced computational methods to characterize development of functional brain networks implicated in EF, and whole brain topology (community structure) from birth to 1 year of age. These brain metrics will be examined as predictors of EF skills at 2 years of age (Aim 1). Prenatal maternal cortisol will be examined as an index of in utero biological stress exposure that is a likely condut for the effects of multiple sources of psychosocial stress on fetal brain development. The applicant will examine cumulative prenatal stress exposure and stress during specific sensitive periods (trimesters) as predictors of brain metrics associated with EF skills. Finally, the applicat will test a full mediational model of the effects of prenatal stress on EF through functional brain development (Aim 2). This work has potential to shed light on early neurobiological markers of risk for poor EF, and sensitive periods in the development of brain systems underlying EF. Longitudinal, multi-method research of this kind is essential for developing comprehensive models linking early stress exposure, brain development and behavioral phenotypes relevant to mental health. Fellowship training will focus on specific content areas, including prenatal stress and brain development, advanced computational methods for rs-fcMRI, longitudinal multivariate statistics, and EF. Importantly, training will also emphasize career development objectives specific to the applicant's planned program of research, including a focus on collaborative interdisciplinary research.

Public Health Relevance

Although the capacity to engage in purposeful, goal-directed behaviors, known as executive functioning, has been identified as key factor in determining risk for psychopathology, very little is known about the early development of brain systems that support this capacity. The proposed research employs a highly innovative approach to examine the neurodevelopmental processes that precede the emergence of executive functioning skills in early childhood, and the extent to which these processes are shaped by stress exposure during pregnancy. Explication of the earliest biomarkers and experiential factors that influence executive functioning has great potential to increase understanding of risk, and to provide targets for early intervention.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Sarampote, Christopher S
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Oregon Health and Science University
Other Basic Sciences
Schools of Medicine
United States
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Graham, Alice M; Pears, Katherine C; Kim, Hyoun K et al. (2018) Effects of a school readiness intervention on hypothalamus-pituitary-adrenal axis functioning and school adjustment for children in foster care. Dev Psychopathol 30:651-664
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Rudolph, Marc D; Graham, Alice M; Feczko, Eric et al. (2018) Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring. Nat Neurosci 21:765-772
Graham, Alice M; Buss, Claudia; Rasmussen, Jerod M et al. (2016) Implications of newborn amygdala connectivity for fear and cognitive development at 6-months-of-age. Dev Cogn Neurosci 18:12-25
Graham, Alice M; Pfeifer, Jennifer H; Fisher, Philip A et al. (2015) The potential of infant fMRI research and the study of early life stress as a promising exemplar. Dev Cogn Neurosci 12:12-39
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Graham, Alice M; Pfeifer, Jennifer H; Fisher, Philip A et al. (2015) Early life stress is associated with default system integrity and emotionality during infancy. J Child Psychol Psychiatry 56:1212-22