Longitudinal Analysis of Neural Network Development in Preterm Infants

Abstract

Application of resting state functional connectivity magnetic resonance imaging (fcMRI) to the study of prematurely born infants enables assessment of the earliest forms of cerebral connectivity and characterization of its early development in the human brain. We obtained 90 longitudinal fcMRI data sets from a cohort of preterm infants aged from 26 weeks postmenstrual age (PMA) through term equivalent age at PMA-specific time points. Utilizing seed-based correlation analysis, we identified resting state networks involving varied cortical regions, the thalamus, and cerebellum. Identified networks demonstrated a regionally variable age-specific pattern of development, with more mature forms consisting of localized interhemispheric connections between homotopic counterparts. Anatomical distance was found to play a critical role in the rate of connection development. Prominent differences were noted between networks identified in term control versus premature infants at term equivalent, including in the thalamocortical connections critical for neurodevelopment. Putative precursors of the default mode network were detected in term control infants but were not identified in preterm infants, including those at term equivalent. Identified patterns of network maturation reflect the intricate relationship of structural and functional processes present throughout this important developmental period and are consistent with prior investigations of neurodevelopment in this population.

The emergence of functional architecture during early brain development

“…Comparable functional network architecture has been revealed in the neonatal brain, albeit in an immature state (Doria et al, 2010a;Fransson et al, 2009;Gao et al, 2014aGao et al, , 2014bGao et al, , 2013Gao et al, , 2009Lin et al, 2008;Smyser et al, 2010) (Figure 3). Primary networks can be clearly depicted in newborn infants and display a mature configuration whilst higher-order networks are largely fragmented (Doria et al, 2010a;Fransson et al, 2009;Gao et al, 2014aGao et al, , 2014bSmyser et al, 2010).…”

“…However, alterations in the global framework of brain wiring have not been observed and are unlikely in the absence of major brain lesions (Bütefisch, 2004). The adverse effects of preterm birth have predominantly been noted to affect the quality of connections rather than their overall layout (Ball et al, , 2013Doria et al, 2010a;Scheinost et al, 2015;Smyser et al, 2010;Toulmin et al, 2015).…”

“…A number of studies have focused on the emergence of resting-state networks in fetuses and newborn infants (Alcauter et al, 2015a;Arichi et al, 2010;Fransson et al, 2009, Gao et al, 2014a, 2014b, 2009Lin et al, 2008;Schöpf et al, 2012;Smyser et al, 2010;Thomason et al, 2015). In healthy adults, a distinct set of resting-state networks has been described encompassing brain regions involved in primary functions (i.e.…”

“…Primary networks can be clearly depicted in newborn infants and display a mature configuration whilst higher-order networks are largely fragmented (Doria et al, 2010a;Fransson et al, 2009;Gao et al, 2014aGao et al, , 2014bSmyser et al, 2010). These higher order networks are merely restricted to their core regions in the newborn brain, exhibiting relatively limited functional connections with spatially distant homologues.…”

“…The default mode network for instance -that has been associated with self-awareness, future planning, mind wandering and conceiving the perspectives of others ('theory of mind') in healthy adult brain functioning -, extends the posterior cingulate cortex, ventral and dorsal medial prefrontal cortex, inferior parietal lobule, lateral temporal cortex and the hippocampus regions in the adult human brain (Buckner et al, 2008;Buckner and Carroll, 2007;Raichle et al, 2001). In neonates, the default mode network is immature and incomplete, encompassing frontal and association cortices including the medial prefrontal cortex and posterior cingulate cortex (Doria et al, 2010a;Gao et al, 2014aGao et al, , 2009Smyser et al, 2010) (Figure 4). A fragmented precursor of the default mode network, comprising the medial prefrontal cortex and posterior cingulate cortex, was recently also identified in the developing fetal brain from 35 PCW (Thomason et al, 2015).…”