Functional thalamocortical connectivity at term equivalent age and outcome at 2 years in infants born preterm

Hilary Toulmin,Jonathan O'Muircheartaigh,Serena J Counsell,Shona Falconer,Andrew Chew,Christian F Beckmann,A David Edwards

doi:10.1016/j.cortex.2020.09.022

Abstract

Infants born preterm are at high risk of long-term motor and neurocognitive deficits. In the majority of these infants structural MRI at the time of normal birth does not predict motor or cognitive outcomes accurately, and many infants without apparent brain lesions later develop motor and cognitive deficits. Thalamocortical connections are known to be necessary for normal brain function; they develop during late fetal life and are vulnerable to perinatal adversity. This study addressed the hypothesis that abnormalities in the functional connectivity between cortex and thalamus underlie neurocognitive impairments seen after preterm birth. Using resting state functional connectivity magnetic resonance imaging (fMRI) in a group of 102 very preterm infants without major focal brain lesions, we used partial correlations between thalamus and functionally-derived cortical areas to determine significant connectivity between cortical areas and thalamus, and correlated the parameter estimates of these connections with standardised neurocognitive assessments in each infant at 20 months of age. Pre-motor association cortex connectivity to thalamus correlates with motor function, while connectivity between primary sensory-motor cortex and thalamus correlates with cognitive scores. These results demonstrate the importance and vulnerability of functional thalamocortical connectivity development in the perinatal period for later neurocognitive functioning.

Highlights

This study addressed the hypothesis that abnormalities in the functional connectivity between cortex and thalamus underlie neurocognitive impairments seen after preterm birth
There was no correlation between the classification of no/mild/moderate abnormality on MRI at birth and motor outcome: this was true for those classified as having moderate abnormality at term compared with those with no abnormality (p 1⁄4 .31) as well as for moderate abnormality compared with mild abnormality (p 1⁄4 .49) and mild compared with no abnormality (p 1⁄4 .52)
In the absence of overt injury, prognostic markers of later child outcome in the preterm born brain are lacking. These results demonstrate the vulnerability of functional thalamocortical connections to the effects of preterm birth and the possibility of using this mechanism to predict outcomes for children who are currently known to be at risk from adverse neurodevelopmental outcome due to prematurity

Summary

Introduction

Preterm birth is the leading cause of child deaths in highincome countries (Litt et al, 2012) and has lifelong neurodevelopmental effects and increased risk of chronic disease stretching into adulthood (Aarnoudse-Moens, Weisglas-Kuperus, van Goudoever, & Oosterlaan, 2009; Boardman et al, 2010; Dyet et al, 2006; Linsell, Malouf, Morris, Kurinczuk, & Marlow, 2015; Nagy, Lagercrantz, & Hutton, 2011; Nosarti et al, 2014; Wood et al, 2005). T1 and T2 weighted MR imaging at the time of normal birth is not precising in detecting infants who develop later neuromotor or neurocognitive problems, failing to detect around 1/3 of the children with impairments (Edwards et al, 2018) These infants who do not have major structural abnormalities at birth are at high risk of motor (Grunewaldt et al, 2014; Spittle et al, 2013), cognitive and language (Larroque et al, 2008; Moore et al, 2012), social, emotional and psychiatric problems (Delobel-Ayoub et al, 2006; Kuzniewicz et al, 2014), difficulties which persists into late childhood and adult life (Akshoomoff et al, 2017; Johnson et al, 2009; Linsell et al, 2018; Litt et al, 2012; Northam et al, 2012; Nosarti et al, 2012).

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