Resting-state network complexity and magnitude changes in neonates with severe hypoxic ischemic encephalopathy

Abstract

Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 term-born infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital (approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016409) and the protocol version is 1.0.

Keywords: brain functional connectivity; brain networks; clustering coefficient; hypoxic ischemic encephalopathy; local efficiency; neonates; nerve regeneration; neural regeneration; resting-state functional magnetic resonance imaging; small-world organization.

Figure 1

Flow chart of the study procedure. HIE: Hypoxic ischemic encephalopathy; MRI: magnetic resonance imaging; fMRI: functional magnetic resonance imaging.

Figure 2

Topological properties of functional networks in mild vs. severe HIE groups. The light blue color represents the mild HIE group and the dark blue represents the severe HIE group. For normalized L_p and normalized C_p, γ > 1 and λ ≈ 1. For E_loc and C_p, all thresholds were significantly greater in the mild HIE group compared with the severe HIE group (P < 0.05). Data are expressed as the mean ± SD (two-sample t-test). HIE: Hypoxic ischemic encephalopathy.

Figure 3

Distribution of hub regions in the functional structural networks of mild and severe HIE patients, nodes with decreased efficiency in severe HIE patients. (A, B) Three-dimensional representation of hub distributions in the mild (A) and severe (B) HIE groups. The hub nodes are shown in blue with node sizes, indicating their nodal efficiency values. (C) The disrupted nodes in severe patients are shown in red with node sizes, indicating the significance of between-group differences in regional efficiency. Data visualized using BrainNet Viewer software (http://www.nitrc.org/projects/bnv/). HIE: Hypoxic ischemic encephalopathy.