Prenatal Drug Exposure and Early Brain Development: Their Relationships, Behavioral Implications, and Brain-Based Prediction of Risks

• In Event: Associations Between Prenatal Biological Environmental Factors and Brain Development in Infancy

Abstract

Prenatal drug exposure (PDE) is known to affect fetal brain development through a variety of mechanisms including maternal physiology, placental function, and direct disruptions of endogenous neural signaling. Consistently, adverse effects of PDE on developmental outcomes in different domains, including learning, memory, attention, emotion regulation, and executive functions are frequently reported. However, the brain basis for these PDE-related cognitive and behavioral disruptions remains elusive. Such characterization is especially important during the infancy period, when the brain growth is the most dynamic and the potential PDE effects are minimally confounded by other postnatal risk factors. In this talk, I will briefly describe our recent findings on neonatal functional connectivity alterations associated with PDE based on resting-state fMRI scans of the infant brain. Specifically, at the circuit level, neonatal amygdala and thalamic functional connectivity disruptions associated with prenatal cocaine exposure and different limbic and thalamic connectivity alterations associated with prenatal marijuana exposure will be firstly described. Following that, findings from a systematic survey of the effects of six different drug types (i.e., opioids, cocaine, marijuana, alcohol, nicotine, and SSRIs) on the whole brain connections will be presented featuring drug-specific “heatmaps” highlighting the mostly-impacted brain areas by different drugs in the newborn brain. The cumulative drug-related effects will also be compared with those associated with other non-drug factors including sex, gestational age at birth/scan, birth weight, and maternal depression. The behavioral implications associated with the PDE-affected functional connections will be discussed. Partly inspired by these brain-behavior association studies in both our PDE and typically developing samples, we have examined a novel concept of relationship-level heterogeneity in newborns and demonstrated the existence of two subgroups of infants with contrasting brain-behavioral mechanisms. The related results will be discussed in this talk. Finally, I will describe some of our most recent findings on a new imaging-based prediction framework to identify later behavioral outliers based on rsfMRI scans from the newborn brain. Based purely on neonatal rsfMRI data, this approach is able to identify >40% of IQ outliers at 4 years of age with a high specificity of 96.2%. Such an approach holds great potential to help identify newborns at risk to develop later abnormal behavioral outcomes, including those with prenatal drug exposures. The successful detection of risk as early as in neonatal stage will greatly facilitate effective interventions for better outcomes.

Author

• Wei Gao, Cedars Sinai Medical Center
  Presenting Author