Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity

Abstract

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks ( SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero .

Empirical evaluation of human fetal fMRI preprocessing steps

“…In addition to shedding light on the origins of typical neural development, fetal RSFC studies also inform our understanding of health risk. For instance, exposures like prenatal stress ( Thomason et al, 2021a ), cannabis ( Thomason et al, 2021b ), and lead ( Thomason et al, 2019 ) have been linked to altered fetal neurodevelopment, which has important implications for policy and intervention. Taken together, this work highlights that fetal MRI is a crucial tool for understanding typical and atypical human neurodevelopment and for uncovering the earliest origins of disease risk.…”

Prenatal delta-9-tetrahydrocannabinol exposure alters fetal neurodevelopment in rhesus macaques

“…This is also the first study to longitudinally examine the impacts of THC on fetal brain development across gestation using in utero MRI techniques. A prior human study examined the impact of prenatal cannabis exposure on human fetal brain hippocampal functional connectivity using functional MRI at a single time point in the mid-third trimester 30 . Thomason et al 30 , found that maternal cannabis use was associated with changes in the fetal neural connectome, specifically fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity.…”

Fetal Hippocampal Connectivity Shows Dissociable Associations with Maternal Cortisol and Self-Reported Distress during Pregnancy

“…Without additional information about the relevance of this hippocampal difference to future development, it is difficult to interpret this elevated connectivity as a risk or protective response in the brain, or to determine whether it is a transient association without long-term ramifications for child development. Although stress-related neural differences are often conceptualized as harmful in nature, one study found that relatively stronger functional coupling between the hippocampus and posterior parietal cortex in fetuses was prospectively correlated with fewer behavioral and executive functioning problems and greater school readiness at age five [ 60 ]. It is therefore possible that our finding of stronger fetal hippocampus–parietal connectivity in the context of acute stress may be an adaptive neural response that prepares offspring to navigate changing environments.…”