Altered functional network connectivity in preterm infants: antecedents of cognitive and motor impairments?

Abstract

Very preterm infants (≤ 31 weeks gestational age) are at high risk for brain injury and delayed development. Applying functional connectivity and graph theory methods to resting state MRI data (fcMRI), we tested the hypothesis that preterm infants would demonstrate alterations in connectivity measures both globally and in specific networks related to motor, language and cognitive function, even when there is no anatomical imaging evidence of injury. Fifty-one healthy full-term controls and 24 very preterm infants without significant neonatal brain injury, were evaluated at term-equivalent age with fcMRI. Preterm subjects showed lower functional connectivity from regions associated with motor, cognitive, language and executive function, than term controls. Examining brain networks using graph theory measures of functional connectivity, very preterm infants also exhibited lower rich-club coefficient and assortativity but higher small-worldness and no significant difference in modularity when compared to term infants. The findings provide evidence that functional connectivity exhibits deficits soon after birth in very preterm infants in key brain networks responsible for motor, language and executive functions, even in the absence of anatomical lesions. These functional network measures could serve as prognostic biomarkers for later developmental disabilities and guide decisions about early interventions.

Cortical Gray Matter Injury in Encephalopathy of Prematurity: Link to Neurodevelopmental Disorders

“…Collectively, these resting state studies suggest that there is modular organization of the connectivity of the preterm brain, as is seen in the mature brain, but that integration between networks is altered ( 172 – 174 ). In these studies, there is evidence for disruption in both cortico-cortical and cortico-subcortical networks ( 172 , 174 ), and reduced connectivity between areas associated with motor function, cognition, language, and executive function ( 173 ).…”

Current Evidence on Cell Death in Preterm Brain Injury in Human and Preclinical Models

“…As mentioned in the Introduction, EoP that covers the different injury patterns related to premature birth can affect either the WM or GM but, depending on the nature and the severity of the lesion, the extent of brain lesions could vary strongly between the individuals. With new emerging MRI techniques, better characterization of EoP now became possible and opens new understanding, such as functional connectivity, diffusion tensor imaging, fractional anisotropy measures and fiber tractography, and automated segmentation techniques for volume determination and growth (Ball et al, 2013;Gozdas et al, 2018;Schneider et al, 2018;Duerden et al, 2019;Jakab et al, 2019). The most prominent findings of EoP in VPT are (1) decreased global brain volume due to white (WM) and gray matter reduction [(GM); cortical GM as well as deep nuclear GM], (2) hydrocephalus ex vacuo (CSF), and (3) connectivity impairment (Dubois et al, 2008;Ball et al, 2013;Chau et al, 2013;Kidokoro et al, 2013;Friedrichs-Maeder et al, 2017;Gozdas et al, 2018;Duerden et al, 2019;Jakab et al, 2019).…”

“…However, less severe brain lesions as in non-cystic and diffuse WM injury (detected by advanced MRI techniques and characterized by astrogliosis and microgliosis) are now more frequently observed with some features of cell death. On the other hand, subtler brain alterations can reflect disturbances of brain development or delay in brain maturation and affect functional connectivity with no apparent cell death (Ball et al, 2013;Gozdas et al, 2018).…”

Predictors of Cognitive Defects and Its Prevention Capabilities in Premature Infants

“…Таким образом, функциональная МРТ, выполненная при выписке из ОРИТН, может расцениваться как имеющая несомненную прогностическую значимость, поскольку выявленные с ее помощью нарушения не обнаруживаются при рутинной структурной МРТ, последняя выявляет предикторы преимущественно грубых органических расстройств. Так, недавно были выполнены исследования, установившие достоверные связи между повреждением белого мозгового вещества лобной доли и когнитивными исходами у недоношенных детей [14,77]. В этой связи заслуживает внимания работа, посвященная становлению функциональных сетей у новорожденных с перинатальными поражениями нервной системы [78].…”