Effects of prenatal opioid exposure on functional networks in infancy

Abstract

Prenatal opioid exposure has been linked to altered neurodevelopment and visual problems such as strabismus and nystagmus. The neural substrate underlying these alterations is unclear. Resting-state functional connectivity MRI (rsfMRI) is an advanced and well-established technique to evaluate brain networks. Few studies have examined the effects of prenatal opioid exposure on resting-state network connectivity in infancy. In this pilot study, we characterized network connectivity in opioid-exposed infants (n = 19) and controls (n = 20) between 4–8 weeks of age using both a whole-brain connectomic approach and a seed-based approach. Prenatal opioid exposure was associated with differences in distribution of betweenness centrality and connection length, with positive connections unique to each group significantly longer than common connections. The unique connections in the opioid-exposed group were more often inter-network connections while unique connections in controls and connections common to both groups were more often intra-network. The opioid-exposed group had smaller network volumes particularly in the primary visual network, but similar network strength as controls. Network topologies as determined by dice similarity index were different between groups, particularly in visual and executive control networks. These results may provide insight into the neural basis for the developmental and visual problems associated with prenatal opioid exposure.

Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure

“…To date, ours is the largest cohort study focused on infants with POE. While Merhar et al also studied global brain networks in infants with POE, and their results suggest correlations of brain connectivity with Finnegan score, we did not find any such correlation in our study, which is likely due to the differences in methodology, as we used the CAP method for brain network assessment after controlling for gestational age and sex ( 27 ). Additionally, we also identified alterations in infant brain resting state functional network connectivity associated with maternal psychological factors.…”

“…There have been a few recent small cohort studies showing alterations in brain resting state functional connectivity in infants with prenatal opioid exposure ( 27 , 28 ). To date, ours is the largest cohort study focused on infants with POE.…”

“…This suggests a role of the interplay between maternal opioid use and psychological disorders on the developing infant brain. Brain resting state functional networks exist in infants and have recently been shown to be altered in the presence of prenatal exposure to substances (27,28,57). However, prenatal substance exposure has also shown to be associated with alterations in multiple other brain regions, both intra-network and inter-network, outside of these canonical resting state functional networks (57).…”

“…There are a small handful of neuroanatomical studies published so far that have evaluated POE in the fetus, neonate, and infant. These studies have suggested alterations in regional brain volumes (22,23), microstructure (24)(25)(26), and impaired brain functional connectivity (24,27,28). However, these aforementioned studies did not specifically assess for the potential effects of maternal comorbidities.…”

Neural alterations in opioid-exposed infants revealed by edge-centric brain functional networks

“…We recently reported that the brains of POE infants exhibited smaller network volumes, particularly in the primary visual network, and different network topologies from controls, particularly in visual and executive control networks. 28 In addition, Radhakrishnan et al 29 reported significant differences in connectivity between an amygdala seed to several cortical regions in POE infants. While these studies revealed potential neural FC alterations in POE infants, they are largely based on a static FC matrix calculated using the entire rs-fMRI scan.…”