The neurobiological correlates of cognitive outcomes in adolescence and adulthood following very preterm birth

Abstract

Very preterm birth (<33 weeks of gestation) has been associated with alterations in structural and functional brain development in regions that are believed to underlie a variety of cognitive processes. While such alterations have been often studied in the context of cognitive vulnerability, early disruption to programmed developmental processes may also lead to neuroplastic and functional adaptations, which support cognitive performance. In this review, we will focus on executive function and intelligence as the main cognitive outcomes following very preterm birth in adolescence and adulthood in relation to their structural and functional neurobiological correlates. The neuroimaging modalities we review provide quantitative assessments of brain morphology, white matter macro and micro-structure, structural and functional connectivity and haemodynamic responses associated with specific cognitive operations. Identifying the neurobiological underpinning of the long-term sequelae associated with very preterm birth may guide the development and implementation of targeted neurobehaviourally-informed interventions for those at high risk.

Introduction

Individuals who were born very preterm (<33 weeks of gestation) are at increased risk of experiencing long-term cognitive difficulties, encompassing executive function and general intelligence, compared to those born at term [[1], [2], [3]] Difficulties in these domains have been associated with real-life achievements in adulthood, including less satisfactory social relationships and lower academic and economic attainments [1], [4].

The exact mechanisms underlying the cognitive sequelae associated with very preterm birth are poorly understood, but they are likely to involve impaired neurodevelopment, as the immature nervous system is vulnerable to exogenous and endogenous insults during the third trimester of gestation, due to its rapidly developing and complex characteristics [5]. Several studies have documented neurobiological alterations in very preterm neonates in brain regions and networks involved in high-order cognitive processes, that have been particularly clearly defined in the thalamocortical tracts [6] and have been shown to predict later neurocognitive function [6,7]. Similar patterns of alterations have been also described in adult survivors of very preterm birth and may at least partly account for their long-term cognitive difficulties [[8], [9], [10], [11]]. Hence, there is an urgent need for research that can aid early identification of the neuroimaging signatures that could identify sub-groups of individuals who are at risk of cognitive sequelae, as these could guide the development and implementation of targeted neurobehaviourally-informed interventions early in life.

In this review we will discuss the results of non-invasive in-vivo magnetic resonance imaging (MRI) studies in very preterm adolescents and adults that have investigated brain morphology, white matter macro and micro-structure, structural and functional connectivity and haemodynamic responses associated with and potentially mediating intelligence and executive function outcomes.

We define intelligence as the “ability to understand complex ideas, to adapt effectively to the environment, to learn from experience, to engage in various forms of reasoning, to overcome obstacles by taking thought” [12]. Intelligence has been subdivided into “fluid intelligence” (cognitive processes applied in non-routine, novel or complex tasks) and “crystallised intelligence” (cognitive abilities related to previously acquired knowledge). Intelligence quotient (IQ) scores assess the performance of individuals on intelligence tests. Executive function, on the other hand, refers to cognitive processes responsible for the execution of goal-oriented tasks and include decision-making, planning, task-switching, inhibitory control, working memory, cognitive flexibility and verbal fluency [13].

Although intelligence and executive functions possess overlapping features and some studies have used the terms interchangeably, others have found that not all executive functions (for instance, the ability to inhibit prepotent responses and to shift mental sets) correlate with IQ (see Ref. [14] for review). We have previously reported lower executive function scores in very preterm adults compared to controls independently of IQ [1,15]. However, at the neuroanatomical level, it is challenging to disentangle regions specific to a single cognitive domain, as both executive function and intelligence are sub-served by a “multiple-demand” brain network, encompassing fronto-parietal cortical regions, basal ganglia, thalamus and cerebellum [16].