Resting-State Network Complexity and Magnitude Are Reduced in Prematurely Born Infants

Abstract

Premature birth is associated with high rates of motor and cognitive disability. Investigations have described resting-state functional magnetic resonance imaging (rs-fMRI) correlates of prematurity in older children, but comparable data in the neonatal period remain scarce. We studied 25 term-born control infants within the first week of life and 25 very preterm infants (born at gestational ages ranging from 23 to 29 weeks) without evident structural injury at term equivalent postmenstrual age. Conventional resting-state network (RSN) mapping revealed only modest differences between the term and prematurely born infants, in accordance with previous work. However, clear group differences were observed in quantitative analyses based on correlation and covariance matrices representing the functional MRI time series extracted from 31 regions of interest in 7 RSNs. In addition, the maximum likelihood dimensionality estimates of the group-averaged covariance matrices in the term and preterm infants were 5 and 3, respectively, indicating that prematurity leads to a reduction in the complexity of rs-fMRI covariance structure. These findings highlight the importance of quantitative analyses of rs-fMRI data and suggest a more sensitive method for delineating the effects of preterm birth in infants without evident structural injury.

Keywords: developmental neuroimaging; functional MRI; infant; prematurity; resting-state networks.

Figure 1.

Regions of interest (ROIs) used in present analyses. Axial, coronal, and sagittal planes are identified by atlas z, y, and x coordinates, respectively. Each resting-state network is represented by 4–6 ROIs (Table 3). (A) language (LAN) network; (B) somatomotor network (SMN); (C) visual (VIS) network; (D) default mode network (DMN); (E) dorsal attention network (DAN); (F) ventral attention network (VAN); (G) frontoparietal control (FPC) network. ROIs are overlaid on the neonate-specific, T₂-weighted atlas template.

Figure 2.

Group mean rs-fMRI correlation maps illustrating the language (LAN), somatomotor (SMN), and visual (VIS) RSNs. The illustrated quantity is the Fisher's z-transformed correlation coefficient (z(r)), averaged and subjects; color threshold |z(r)| > 0.12. For all maps, the seed ROI is the first listed in Table 3. (A) Term infants; (B) preterm infants studied at term equivalent postmenstrual age. Note the presence of both positive (warm hues) and negative (cool hues) correlations. Underlay image and atlas plane labeling as in Figure 1.

Figure 3.

Group mean Fisher's z-transformed correlation coefficient matrices representing all ROI pairs. The block structure along the diagonal corresponds to RSNs. (A) Term infants; (B) preterm infants; (C) term minus preterm difference. Black stars in (C) denote cells with a significant (P < 0.05; multiple comparisons uncorrected) between group difference on two-tailed t-test. Note similarity of block structure in (A) and (B).

Figure 4.

Group mean covariance matrices representing all pairs of ROIs. The block structure corresponds to RSNs. (A) Term infants; (B) preterm infants; (C) term minus preterm difference. Black stars in (C) denote cells with a significant (P < 0.05; multiple comparisons uncorrected) between group difference on two-tailed Mann–Whitney U-test. Note similarity of block structure in (A) and (C). This similarity reflects roughly proportional down-scaling of positive and negative rs-fMRI covariance values in the preterm group relative to the term group.

Figure 5.

Scatter plots of group difference versus group mean functional connectivity results for all pairs of ROIs (depicts same data as in Figs 3 and 4). (A) Fisher's z-transformed correlations; (B) covariance values. In (B), the slope of the difference on mean regression line is 0.72, indicating that preterm covariance values are, on average, approximately one half those of term values.

Figure 6.

Quantitative rs-fMRI measures. (A) Group mean Fisher's z-transformed correlation coefficients between homotopic ROIs pairs. Note consistent term > preterm correlation values. (B) Scree plots corresponding to the covariance matrices shown in Figure 4. The maximum likelihood dimensionality estimates are 5 and 3 for term and preterm infants, respectively.