Interactive Effects of Prenatal Drug Exposure and Socioeconomic Status on Early Brain Connectivity

405 

Abstract Submission 

Gabriella Vavala¹, Janelle Liu¹, Rina Eiden², Karen Grewen³, Wei Gao¹

¹Biomedical Imaging Research Institute (BIRI), Cedars-Sinai Medical Center, Los Angeles, CA, ²Pennsylvania State University, University Park, PA, ³University of North Carolina at Chapel Hill, Chapel Hill, NC

Gabriella Vavala  
Biomedical Imaging Research Institute (BIRI), Cedars-Sinai Medical Center
Los Angeles, CA

Janelle Liu  
Biomedical Imaging Research Institute (BIRI), Cedars-Sinai Medical Center
Los Angeles, CA

Rina Eiden  
Pennsylvania State University
University Park, PA

Karen Grewen  
University of North Carolina at Chapel Hill
Chapel Hill, NC

Wei Gao  
Biomedical Imaging Research Institute (BIRI), Cedars-Sinai Medical Center
Los Angeles, CA

Prenatal drug exposure (PDE) and socioeconomic status (SES) are known to independently affect newborn brain functional network development (Gao 2015, Salzwedel 2015, Liu 2022). Resting-state functional magnetic resonance imaging (rsfMRI) studies in infants and children with PDE show connectivity disruptions in limbic regions involved in reward processing and emotion regulation (Morie 2019, Ross 2015, Salzwedel 2015, Liu 2022). SES has also been linked with infant functional connectivity development in the default-mode network (Gao 2015). However, little is known about the combined effect of PDE and SES on early neurodevelopment. In this study, we used rsfMRI to examine both the unique and potentially interactive effects of PDE and SES (i.e., indexed by maternal education (MEdu)) on functional connectivity at birth.

Participants were enrolled as part of two projects examining the impact of PDE on early brain development. Subjects in both datasets included drug-free control neonates (CTR; Dataset 1: n=54; Dataset 2: n=28) and neonates with PDE (Dataset 1: n=61; Dataset 2: n=81), including: alcohol, nicotine, marijuana, cocaine, and opioids. Data from 100 drug-free control neonates from the University of North Carolina Early Brain Development Study (reference dataset; Gao 2017; Gilmore 2018) were also used. For all datasets, rsfMRI scans were acquired during natural sleep at 2 weeks of age. Participants were matched on sex, race, age at birth, age at scan, and motion. Birthweight and maternal depression were included as covariates of no interest in all analyses. Functional connectivity measures were derived using a neonate functional parcellation-based atlas (Shi 2018). For each seed region of interest (ROI; n=223), the average time series was extracted and correlated with every other ROI in the brain to compute a correlation matrix for each subject. Linear regression was used to identify main effects (PDE, MEdu) as well as interactive effects (PDExMEdu) on each neonate functional connection. A p-value thresholding strategy (p<.05) was used to generate heatmaps revealing main effects of PDE, main effects of MEdu, and interactive effects between PDE and MEdu on functional connectivity between each ROI and the whole brain.

In Dataset 1, main effects of PDE and MEdu were concentrated in similar regions, including temporal, frontal, and occipital areas. Additionally, there was a main effect of PDE, but not MEdu, in the left mid-cingulate gyrus. Significant interaction effects were observed in frontal, temporal, occipital, and mid-cingulate regions. A different distribution of effects was observed in Dataset 2. Main effects of PDE were observed in the left mid-cingulate gyrus, right anterior cingulate gyrus, orbitofrontal cortex, and fusiform gyrus. Widespread effects were observed for MEdu, concentrated in the anterior cingulate gyrus as well as frontal, parietal, and occipital areas. Significant interaction effects were observed in Dataset 2, driven by PDE. Across both datasets, the main effect of PDE on mid-cingulate gyrus was highly consistent.

At birth, distinct effects on functional connectivity are observed for both PDE and MEdu. In line with prior studies in children and youth with PDE demonstrating altered structure and function of the cingulate cortex (Morie 2019, Ross 2015), we observed a significant effect of PDE on mid-cingulate functional connectivity across both datasets. Importantly, wide-spread interactive effects were also observed, indicating that the two risk factors may combine and interact with each other to have differential impacts on pre-/perinatal functional connectivity development depending on the situation. Between the two datasets, we observed markedly different distributions of the effects of PDE and MEdu as well as the interactive effects between PDE and MEdu, which may be due to the heterogeneous polydrug profiles in this population.

Neurodevelopmental/ Early Life (eg. ADHD, autism) ¹

Education, History and Social Aspects of Brain Imaging

Normal Brain Development: Fetus to Adolescence

Connectivity (eg. functional, effective, structural)

fMRI Connectivity and Network Modeling ²

Cognition

Development

FUNCTIONAL MRI

PEDIATRIC

Other - connectivity; infant; prenatal drug exposure; socioeconomic status