Altered resting-state functional connectivity in children and adolescents born very preterm short title

Abstract

The formation of resting-state functional networks in infancy has been reported to be strongly impacted by very preterm birth. Studies in childhood and adolescence have largely focused on language processing networks and identified both decreased and increased functional connectivity. It is unclear, however, whether functional connectivity strength is altered globally in children and adolescents born very preterm and whether these alterations are related to the frequently occurring cognitive deficits. Here, resting-state functional MRI was assessed in a group of 32 school-aged children and adolescents born very preterm with normal intellectual and motor abilities and 39 healthy term-born peers. Functional connectivity within and between a comprehensive set of well-established resting-state networks was compared between the groups. IQ and executive function abilities were tested with standardized tasks and potential associations with connectivity strength were explored. Functional connectivity was weaker in the very preterm compared to the term-born group between the sensorimotor network and the visual and dorsal attention network, within the sensorimotor network and within the central executive network. In contrast, functional connectivity was stronger in the very preterm group between the sensorimotor network and parts of the salience and the central executive network. Little evidence was found that these alterations underlie lower IQ or poorer executive function abilities. This study provides evidence for a long-lasting impact of very preterm birth on the organization of resting-state networks. The potential consequence of these alterations for other neurodevelopmental domains than the ones investigated in the current study warrants further investigation.

Changes of Dynamic Functional Connectivity Associated With Maturity in Late Preterm Infants

“…However, some late preterm infants without obvious structural changes also have developmental and emotional-behavioral problems in childhood and adolescence. Previous study has provided evidence for an aberrant structural and functional connectivity in preterm infants and a long-lasting impact of preterm birth on the organization of resting-state networks in school-aged children and adolescents (21,22). Nonetheless, previous rs-fMRI studies of premature infants were mostly performed when they reached term equivalent age (23)(24)(25).…”

Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm

“…Similar approaches have been used previously to estimate global executive function abilities in children born very preterm. 47 , 48 …”

Impact of non‐CNS childhood cancer on resting‐state connectivity and its association with cognition

“…Stronger as well as weaker connectivity was also described in studies with other patients, such as i.e. preterm‐born children at school‐age (Finke et al., 2015; Wehrle et al., 2018), children with ADHD (Jiang et al., 2019), or adults after traumatic brain injury (Hillary et al, 2011).…”

“…Additionally, stronger functional connectivity has been reported in adult survivors of childhood brain tumors and in adult patients with other neurological diseases (Audoin et al., 2003; Chen et al., 2016; Staffen et al., 2002; Sweet et al., 2006). Overall, the impact of increased connectivity strength has been discussed in various ways, including possible adaption mechanism employed by the brain to cope with early disease or neurotoxicity (Wehrle et al., 2018). Our findings of hyperconnectivity in survivors after CNS‐directed therapy (when compared to non‐CNS‐directed therapy) support the model of adaptation mechanisms of the brain to early events such as CC.…”