Annual Research Review: Not just a small adult brain: understanding later neurodevelopment through imaging the neonatal brain

Abstract

Background: There has been a recent proliferation in neuroimaging research focusing on brain development in the prenatal, neonatal and very early childhood brain. Early brain injury and preterm birth are associated with increased risk of neurodevelopmental disorders, indicating the importance of this early period for later outcome.

Scope and methodology: Although using a wide range of different methodologies and investigating diverse samples, the common aim of many of these studies has been to both track normative development and investigate deviations in this development to predict behavioural, cognitive and neurological function in childhood. Here we review structural and functional neuroimaging studies investigating the developing brain. We focus on practical and technical complexities of studying this early age range and discuss how neuroimaging techniques have been successfully applied to investigate later neurodevelopmental outcome.

Conclusions: Neuroimaging markers of later outcome still have surprisingly low predictive power and their specificity to individual neurodevelopmental disorders is still under question. However, the field is still young, and substantial challenges to both acquiring and modeling neonatal data are being met.

Keywords: Prematurity; biomarkers; neurodevelopmental disorders; neuroimaging; perinatal.

Figure 1

T1‐ and T2‐weighted images at different age points throughout the perinatal and early childhood period. Illustrative growth curves for the two periods (adapted from Makropoulos et al., 2016 and Dean III, Dirks et al., 2014) are shown above in blue [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Functional MRI applied to the neonatal brain in both task‐based and resting conditions. For auditory stimulation, provided during natural sleep, adult‐like patterns of voice‐responsive activity become evident (Blasi et al., 2015), (A). Similarly, the activity patterns in response to painful skin stimulation reflects what would be seen in adults (Goksan et al., 2015), (B). Motor cortex responses to a passive motor balloon task become more bilateral from 31 weeks (top row, C) to term age (41 weeks, bottom row, C) (Arichi et al., 2012). Finally the repertoire of resting state networks seen in adults is clearly evident in the neonatal brain at term‐equivalent age (Ball et al., 2016), (D), but the pattern of connectivity between the networks is different in the preterm‐born brain, allowing discrimination [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Network representation of developing microstructure. The correlation of corrected age at MRI with structural connections weighted by NODDI intracellular volume fraction index (or neurite density index, NDI), in a population of 65 infants scanned between 25 and 45 weeks of postmenstrual age (PMA). In panel (A) NDI parameters increase with age for most white matter connections, as would be expected. However, when assessed in relative terms (%) of the total connectivity in each subject (panel B and C), it is possible to separate which connections are developing at a relative faster or slower pace. This clarifies the expected heterochronicity in the early development of brain connectivity, with a general trend of connections between somatosensory, central, subcortical and temporal areas to show faster development (red) than frontolimbic and interhemispheric connections (blue). Adapted from Batalle et al. (2017) [Colour figure can be viewed at http://wileyonlinelibrary.com]