Impact of prenatal cannabis exposure on functional connectivity of the salience network in children

Abstract

Cannabis use among pregnant people has increased over the past decade. This is of concern as prenatal cannabis exposure (PCE) is associated with cognitive, motor, and social deficits among offspring. Here, we examined resting-state functional connectivity (rsFC) of the salience network (SN)-a core neurocognitive network that integrates emotional and sensory information-in children with (vs. without) PCE. Using neuroimaging and developmental history data collected from 10,719 children (M ± SD = 9.92 ± 0.62 years; 47.9% female) from the Adolescent Brain Cognitive Development study, we assessed the impact of parent-reported PCE (before or after knowledge of pregnancy) on rsFC within and between the SN and five other core neurocognitive networks. We also evaluated whether SN rsFC mediated the association between PCE and child psychopathology. Results showed that PCE before (but not after) knowledge of pregnancy was associated with lower SN-ventral attention network (VAN) rsFC. Furthermore, psychotic-like experiences mediated the association between PCE and SN-VAN rsFC, and reversal of the model was also significant, such that SN-VAN rsFC mediated the association between PCE and psychotic-like symptoms. However, these mediation effects were no longer significant after the inclusion of covariates. Taken together, these findings suggest that developmental alterations in SN-VAN interactions may explain the previously reported association between PCE and elevated risk of child psychopathology.

Keywords: endocannabinoid; fMRI; gestational marijuana; neurocognitive; resting-state; salience network.

Figure 1.. Core neurocognitive networks of interest.

SN, salience network; DAN, dorsal attention network; DMN, default mode network; FPN, frontoparietal network; VAN, ventral attention network.Xyz indicates Montreal Neurological Institute (MNI) coordinates.

Figure 2.. Prenatal cannabis exposure (PCE) before knowledge of pregnancy is associated with lower rsFC between the SN and VAN.

Box plots indicate median and first and third quartiles. The sample mean is indicated with an “X”. SN, salience network; PCE, prenatal cannabis exposure; VAN, ventral attention network; rsFC, resting-state functional connectivity. *p < 0.05.

Figure 3:. Mediation analyses.

A: Psychotic-like experiences mediate the association between PCE before knowledge of pregnancy and SN-VAN rsFC. B: Reversal of the model was also significant, such that SN-VAN rsFC mediates the association between PCE before knowledge of pregnancy and psychotic-like symptoms. c = total effect; c’ = direct effect. *p < 0.05, **p < 0.01, ***p < 0.001.