Mapping Longitudinal Trajectories of Functional Connectivity in Prenatal Opioid Exposure
Poster No:
305
Submission Type:
Abstract Submission
Authors:
Janelle Liu1, Haitao Chen2, Wesley Thompson3, Rina Eiden4, Karen Grewen5, Wei Gao6
Institutions:
1Cedars-Sinai Medical Center, Los Angeles, CA, 2University of California, Los Angeles, Los Angeles, CA, 3Laureate Institute for Brain Research, Tulsa, OK, 4The Pennsylvania State University, University Park, PA, 5UNC-CH, CHAPEL HILL, NC, 6Biomedical Imaging Research Institute (BIRI), Cedars-Sinai Medical Center, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
Prenatal opioid exposure (PODE) has widespread effects on neurobehavioral development. Infants with PODE experience deficits in cognitive, motor, and language development and are at an elevated risk of negative outcomes, including deficits in behavioral and emotional regulation. Cross sectional functional magnetic resonance imaging (fMRI) studies of neonates and youth with PODE reveal aberrant brain functional connectivity, but no studies to date have examined how longitudinal development of functional connectivity is impacted by PODE. Here, for the first time, we use resting-state fMRI (rsfMRI) to map longitudinal trajectories of functional connectivity growth over the first year of life. We also examine whether differences in these developmental trajectories are related to behavioral outcomes.
Methods:
Subjects included infants with PODE (n=60), infants with prenatal exposure to other drugs excluding opioids (PDE, n=72), and drug-free controls (CTR, n=43). RsfMRI scans were acquired during natural sleep at 2 weeks, 3 months, 6 months, and 12 months of age. Groups were matched on sex, race, and gestational age at birth. Birthweight, maternal education, neighborhood adversity, and maternal depression were included as covariates of no interest in all analyses to control for group differences in these variables. Functional connectivity measures were derived using a 1-year functional parcellation-based atlas (Shi 2018). Within-network functional connectivity was calculated within seven canonical resting-state networks (visual, sensorimotor, dorsal attention, ventral attention, limbic, frontoparietal, default mode networks; Yeo 2011) as well as a subcortical network. Multivariate sparse functional principal components analysis (mSFPCA) was used to estimate individual smooth trajectories from the longitudinal rsfMRI data (Jiang 2021). Next, linear regression was conducted to detect significant between-group differences in the resulting functional principal components (FPCs) for each network. Lastly, a canonical correlation analysis (CCA) was used to examine brain-behavior associations between longitudinal trajectories of functional connectivity and 12-month measures of cognitive, language, and motor development as indexed by the Bayley Scales of Infant and Toddler Development (BSID; Bayley 2005).
Results:
Different temporal trends were observed for each network across the first year (Fig 1A). Overall, within-network connectivity decreased over time in the sensorimotor and limbic networks, increased over time in the dorsal attention, frontoparietal, default mode, and subcortical networks, and initially increased followed by a slight decrease by the end of the first year in the visual and ventral attention networks. As expected, there were subject-level variations in each network; this additional temporal information is captured by the FPC curves (Fig 1B). On average, the first FPC explained over 90% of the variance for each network. PODE and PDE infants showed divergent functional connectivity growth trajectories in the subcortical network compared with the CTR group (Fig 2A). In the PODE group, longitudinal trajectories of visual, ventral attention, and limbic network connectivity best predicted 12-month outcomes (Fig 2B).
Conclusions:
Taken together, our results provide evidence for cascading effects of PODE on neurodevelopmental trajectories. Across the first year, functional connectivity trajectories increasingly diverge over time in infants with PODE. Longitudinal growth of subcortical network connectivity is differentially impacted by prenatal exposure to opioids and other drugs. Decreasing connectivity within the subcortical network may reflect less differentiation in the connectivity of subcortical regions in infants with PODE/PDE. By contrast, CTR infants showed increasing subcortical network connectivity, which may reflect increasing differentiation of subcortical regions as the functional connectome matures.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Keywords:
Cognition
Development
FUNCTIONAL MRI
PEDIATRIC
Other - Connectivity; Infant; Prenatal drug exposure
1|2Indicates the priority used for review
Abstract Information
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Provide references using APA citation style.
Jiang, L. (2021). Multi-block sparse functional principal components analysis for longitudinal microbiome multi-omics data. Annals of Applied Statistics, 16(4), 2231-2249.
Shi, F. (2018). Functional brain parcellations of the infant brain and the associated developmental trends. Cerebral Cortex, 28(4), 1358-1368.
Yeo, B.T.T. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(3), 1125-1165.