Aberrant structural and functional connectivity and neurodevelopmental impairment in preterm children

Rogers et al. Journal of Neurodevelopmental Disorders https://doi.org/10.1186/s11689-018-9253-x (2018) 10:38 REVIEW Open Access Aberrant structural and functional connectivity and neurodevelopmental impairment in preterm children Cynthia E. Rogers1* , Rachel E. Lean2, Muriah D. Wheelock2 and Christopher D. Smyser3 Abstract Background: Despite advances in antenatal and neonatal care, preterm birth remains a leading cause of neurological disabilities in children. Infants born prematurely, particularly those delivered at the earliest gestational ages, commonly demonstrate increased rates of impairment across multiple neurodevelopmental domains. Indeed, the current literature establishes that preterm birth is a leading risk factor for cerebral palsy, is associated with executive function deficits, increases risk for impaired receptive and expressive language skills, and is linked with higher rates of co-occurring attention deficit hyperactivity disorder, anxiety, and autism spectrum disorders. These same infants also demonstrate elevated rates of aberrant cerebral structural and functional connectivity, with persistent changes evident across advanced magnetic resonance imaging modalities as early as the neonatal period. Emerging findings from cross-sectional and longitudinal investigations increasingly suggest that aberrant connectivity within key functional networks and white matter tracts may underlie the neurodevelopmental impairments common in this population. Main body: This review begins by highlighting the elevated rates of neurodevelopmental disorders across domains in this clinical population, describes the patterns of aberrant structural and functional connectivity common in prematurely-born infants and children, and then reviews the increasingly established body of literature delineating the relationship between these brain abnormalities and adverse neurodevelopmental outcomes. We also detail important, typically understudied, clinical, and social variables that may influence these relationships among preterm children, including heritability and psychosocial risks. Conclusion: Future work in this domain should continue to leverage longitudinal evaluations of preterm infants which include both neuroimaging and detailed serial neurodevelopmental assessments to further characterize relationships between imaging measures and impairment, information necessary for advancing our understanding of modifiable risk factors underlying these disorders and best practices for improving neurodevelopmental trajectories in this high-risk clinical population. Keywords: Prematurity, Neurodevelopmental disorders, Functional connectivity, Structural connectivity, Magnetic resonance imaging * Correspondence: 1 Departments of Psychiatry and Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8504, St. Louis, MO 63110, USA Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. (2018) 10:38 Page 2 of 13 Preterm birth remains a major public health issue due to its high incidence combined with the frequency of neurodevelopmental impairments among surviving infants. In this review, we begin by highlighting the adverse effects of prematurity on trajectories across neurodevelopmental domains. Next, we discuss the increasingly established relationship between aberrant brain development and preterm birth, with particular focus on the advanced magnetic resonance imaging (MRI) techniques increasingly utilized to delineate the changes in cerebral structural and functional connectivity related to prematurity. We then review selected studies from the extant literature which suggest that prematurity-associated changes in cerebral structural and functional connectivity may underlie the neurodevelopmental impairments common among prematurely born children and adults. Finally, we conclude by detailing relevant clinical and social variables that may influence these relationships in this high-risk clinical population. impairment [12]. Similarly, 15–20% of intellectual disabilities and 10–15% of other learning disorders are attributable to preterm birth. VPT children obtain Full Scale Intelligence Quotient (IQ) scores up to 10 points lower than term children [20, 21]. Furthermore, VPT children consistently perform worse than term-born peers on executive function tasks assessing planning, fluency, working memory, and response inhibition [22–24]. Preterm children also demonstrate problems in selective, sustained, and executive attention, with up to 41% of VPT and 62% of extremely preterm (born at < 28 weeks’ gestation) children in the impaired range [25–28]. Further, large effect sizes have been reported for executive shifting and divided attention [25, 26, 29], suggesting VPT children particularly struggle with top-down control of attention processes. In addition, approximately 35% of children born between 31 and 34 weeks’ gestation demonstrate language impairments at preschool-age, with rates as high as 48% for children born at less than 30 weeks gestation [30]. Deficits in both receptive and expressive language domains persist into school age, affecting skills such as word finding, perception, grammar, dialog, and linguistics [30–34]. Critically, across each of these neurodevelopmental domains, preterm birth remains a strong risk factor for impairment even after accounting for sociodemographic risk [19, 35]. More recently, elevated rates of social-emotional deficits and psychiatric disorders have been recognized among children born preterm, with increasing numbers of reports detailing the “preterm behavioral phenotype” [36], comprised of inattention, anxiety, and social-communication deficits [37]. These comorbid symptoms and the related disorders of Attention-deficit hyperactivity disorder (ADHD), anxiety, and autism spectrum disorder (ASD) are two to four times more common among preterm children [5, 38–43]. As with other neurodevelopmental impairments, children born VPT are at greatest risk for these social-emotional impairments and psychiatric diagnoses [36]. Further, studies examining the trajectory of these symptoms demonstrate their persistence into adolescence [5, 44–49]. Importantly, rates of these disorders remain elevated even after accounting for the increased frequency of other neurodevelopmental disabilities, including motor and (...truncated)