Weak functional connectivity in the human fetal brain prior to preterm birth

Moriah E Thomason,Edgar Hernandez-Andrade,Susan Berman,R Todd Constable,Lami Yeo,Laura R Ment,Janessa H Manning,Jasmine Hect,Roberto Romero,Lauren E Grove,Athina Pappas,Narcis Marshall,Dustin Scheinost,Sonia S Hassan

doi:10.1038/srep39286

Abstract

It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.

Highlights

Developmental problems are significantly more common in children born preterm
We investigated the relationship between connectivity and gestational age at fMRI assessment and delivery
Using recent developments in fetal resting-state fMRI we examined neural functional connectivity in 32 human fetuses and found reduced connectional integrity in fetuses that would subsequently be born preterm, in regions of the left hemisphere that later support language processing

Summary

Introduction

Developmental problems are significantly more common in children born preterm. Epidemiological and meta-analytic studies indicate children born preterm are three times more likely to develop autism, attention deficit/hyperactivity disorders, and emotional disorders[1,2], five times more likely to manifest neurological abnormalities[3], and three to four times more likely to experience school failure[4]. Neural irregularities have been observed at the systems level as well, with altered wide-scale network connectional architecture identified in infants born preterm[7,8,9,10]. These studies report diminished coherence of activity measured across brain circuits, indicative of weaker connectivity in individuals born preterm from infancy[11,12] through adulthood[13,14]. A critical target for current research is to separate intrauterine from extrauterine influences on injurious brain development, and to isolate the earliest indicators of change in connectional architecture of the preterm brain. Post-hoc seed analysis was performed to explore the regions in which specific connections were most responsible for changes intrinsic connectivity distribution (ICD)[46] value differences between preterm and full-term groups

Methods

Results

Conclusion