Typical and disrupted brain circuitry for conscious awareness in full-term and preterm infants

Abstract

One of the great frontiers of consciousness science is understanding how early consciousness arises in the development of the human infant. The reciprocal relationship between the default mode network and fronto-parietal networks-the dorsal attention and executive control network-is thought to facilitate integration of information across the brain and its availability for a wide set of conscious mental operations. It remains unknown whether the brain mechanism of conscious awareness is instantiated in infants from birth. To address this gap, we investigated the development of the default mode and fronto-parietal networks and of their reciprocal relationship in neonates. To understand the effect of early neonate age on these networks, we also assessed neonates born prematurely or before term-equivalent age. We used the Developing Human Connectome Project, a unique Open Science dataset which provides a large sample of neonatal functional MRI data with high temporal and spatial resolution. Resting state functional MRI data for full-term neonates (n = 282, age 41.2 weeks ± 12 days) and preterm neonates scanned at term-equivalent age (n = 73, 40.9 weeks ± 14.5 days), or before term-equivalent age (n = 73, 34.6 weeks ± 13.4 days), were obtained from the Developing Human Connectome Project, and for a reference adult group (n = 176, 22-36 years), from the Human Connectome Project. For the first time, we show that the reciprocal relationship between the default mode and dorsal attention network was present at full-term birth or term-equivalent age. Although different from the adult networks, the default mode, dorsal attention and executive control networks were present as distinct networks at full-term birth or term-equivalent age, but premature birth was associated with network disruption. By contrast, neonates before term-equivalent age showed dramatic underdevelopment of high-order networks. Only the dorsal attention network was present as a distinct network and the reciprocal network relationship was not yet formed. Our results suggest that, at full-term birth or by term-equivalent age, infants possess key features of the neural circuitry that enables integration of information across diverse sensory and high-order functional modules, giving rise to conscious awareness. Conversely, they suggest that this brain infrastructure is not present before infants reach term-equivalent age. These findings improve understanding of the ontogeny of high-order network dynamics that support conscious awareness and of their disruption by premature birth.

Keywords: brain development; conscious awareness; high-order networks; neonate; premature birth.

Graphical Abstract

Figure 1

The number of scans included in data analyses. From top to bottom, the middle column indicates the number of scans that passed head motion criteria in each neonate group. TEA, term-equivalent age; vs., versus; FC, functional connectivity.

Figure 2

Within-network and between-network FC across DMN, DAN and ECN in the neonate groups. (A) full-term neonates; (B) preterm neonates scanned at TEA; (C) preterm neonates scanned before TEA. The black lines/asterisks indicate significant difference between FC measures for each network (Paired t-tests), and the blue lines/asterisks indicate significant difference in FC measures of different networks (Paired t-tests). The FC values were Fisher-z transformed and inter-subject variability was removed for display purposes. ** = P < 0.005.

Figure 3

Between-network functional connectivity in neonate groups. (A) full-term neonates; (B) preterm neonates scanned at TEA; (C) preterm neonates scanned before TEA. One-way ANOVAs with repeated measures and Paired t-tests were used here. The FC values were Fisher-z transformed and inter-subject variability was removed for display purposes. DMN−DAN, FC between the DMN and DAN; DMN−ECN, FC between the DMN and ECN; DAN−ECN, FC between the DAN and ECN; **P < 0.005.

Figure 4

FC in adults and neonate groups. (A) adults, (B) full-term neonates, (C) preterm neonates scanned at TEA and (D) preterm neonates scanned before TEA. The FC value presents here was Fisher-z transformed and normalized within each subject before being averaged within each group. R, right; L, left; PCC/Prec, posterior cingulate cortex/precuneus; mPFC, medial prefrontal cortex; lPC, lateral parietal cortex; ITG, inferior temporal gyrus; FEF, frontal eye field; pIPS, posterior intraparietal sulcus; aIPS, anterior intraparietal sulcus; MT, middle temporal area; dmPFC, dorsal medial prefrontal cortex; aPFC, anterior prefrontal cortex; SPC, superior parietal cortex.

Figure 5

The development of the DMN, DAN and ECN in neonates relative to adults. (A) full-term neonates, (B) preterm neonates scanned at TEA and (C) preterm neonates scanned before TEA relative to the adults. The left panels of (A), (B) and (C) depict the comparison of within-network FC between each neonate group and the adults. GLMs were used to test for group differences while controlling for head motion. The FC values were Fisher-z transformed and normalized within each subject before being averaged within each group. The right panels of (A), (B) and (C) depict the network structure of each neonate group relative to adults. Triangles/circles/squares represent the nodes of the DMN/DAN/ECN. R, right; L, left; PCC/Prec, posterior cingulate cortex/precuneus; mPFC, medial prefrontal cortex; lPC, lateral parietal cortex; ITG, inferior temporal gyrus; FEF, frontal eye field; pIPS, posterior intraparietal sulcus; aIPS, anterior intraparietal sulcus; MT, middle temporal area; dmPFC, dorsal medial prefrontal cortex; aPFC, anterior prefrontal cortex; SPC, superior parietal cortex. **P < 0.005.

Figure 6

Multidimensional scaling (MDS) plots of regions in adults and neonates. (A) adults, (B) full-term neonates, (C) preterm neonates scanned at TEA and (D) preterm neonates scanned before TEA. The 2-D plots were created using non-metric MDS based on node’s similarity. Here triangles/circles/squares indicate nodes of the default mode/dorsal attention/executive control network. Abbreviations: 1, posterior cingulate cortex/precuneus; 2, medial prefrontal cortex; 3, left lateral parietal cortex; 4, right lateral parietal cortex; 5, left inferior temporal gyrus; 6, right inferior temporal gyrus; 7, left frontal eye field; 8, right frontal eye field; 9, left posterior intraparietal sulcus; 10, right posterior intraparietal sulcus; 11, left anterior intraparietal sulcus; 12, right anterior intraparietal sulcus; 13, left middle temporal area; 14, right middle temporal area; 15, dorsal medial prefrontal cortex; 16, left anterior prefrontal cortex; 17, right anterior prefrontal cortex; 18, left superior parietal cortex; 19, right superior parietal cortex; TEA, term-equivalent age.

Figure 7

The development of the between-network FC in neonates relative to adults. (A) full-term neonates, (B) preterm neonates scanned at TEA and (C) preterm neonates scanned before TEA relative to the adults. GLMs were used to test for group differences while controlling for head motion. The FC values were Fisher-z transformed and normalized within each subject before averaging within each group. Abbreviations: FC, functional connectivity; DMN−DAN, FC between DMN and DAN; DMN−ECN, FC between DMN and ECN; DAN−ECN, FC between DAN and ECN; P < 0.005.

Figure 8

The effect of premature birth and early neonate age on the development of network FC. (A) The effect of premature birth on within-network FC (the left panel) and between-network FC (the right panel). The FC values represented in (A) were Fisher-z transformed and normalized within each subject before averaging within each group. Independent-sample t-tests were applied to detect the effect of premature birth here. (B) The effect of early neonate age on within-network FC (the left panel) and between-network FC (the right panel). The FC values represented in (B) were Fisher-z transformed, normalized within each subject, and inter-subject variability was removed for display purposes. Paired t-tests were applied to detect the effect of early neonate age here. Abbreviations: DMN, default mode network; DAN, dorsal attention network; ECN, executive control network; DMN−DAN, FC between DMN and DAN; DMN−ECN, FC between DMN and ECN; DAN−ECN, FC between DAN and ECN; **P < 0.005.