Intrinsic functional brain architecture derived from graph theoretical analysis in the human fetus.

Moriah E Thomason,Maya T Dassanayake,Sonia S Hassan,Jesse A Brown,Hilary A Marusak,Edgar Hernandez-Andrade,Swati Mody,Lami Yeo,Rupal Shastri,Roberto Romero,Susan Berman,Daniel Margulies

doi:10.1371/journal.pone.0094423

Abstract

The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

Highlights

A major objective for neuroscience is to build a complete diagram of brain connections at the beginning of human life
This study demonstrates the utility of fetal functional magnetic resonance imaging (fMRI) for discovering principles of neural system organization at the beginning of human life
Our results indicate the fetal brain is organized with modular structure, wherein connections are much stronger within than between modules

Summary

Introduction

A major objective for neuroscience is to build a complete diagram of brain connections at the beginning of human life. By leveraging correlations of low-frequency (,,0.1 Hz) intrinsic fluctuations in the blood oxygen level dependent (BOLD) signal, functional connectivity MRI (fcMRI) provides information about macroscale brain organization. While this method is based on functional signals, intrinsic brain fluctuations have been shown to reflect underlying anatomic pathways [3,4], making this a useful technique for exploring emergent neural circuits in the human fetus. Airline flight routes, migration patterns, social networks, and Twitter feeds all may be studied using graph theory This technique conveys information about overall network infrastructure as well as specific features, such as which ‘nodes’ (locations/individuals) within a system are central ‘hubs’ of connectivity, linking numerous other units to one another. From graph analysis of fMRI datasets we have learned that the human brain is organized with small world topology [6] and that the posterior cingulate and insular cortices are connectivity hubs [7,8,9]

Methods

Results

Conclusion