Structural covariance alterations reveal motor damage in periventricular leukomalacia

Periventricular leukomalacia is a common neuroimaging finding in patients with spastic cerebral palsy. Myelin damage disrupts neuronal connectivity. However, specific alterations in the grey matter structure and their impact on the whole brain remain unclear, particularly when differentiating between preterm and full-term periventricular leukomalacia. This study investigated the grey matter network alterations following early white matter injury in infants and young children. High-resolution T₁-weighted 3 T brain magnetic resonance imaging, clinical data and motor function scores were collected from 42 children with periventricular leukomalacia and 38 age- and sex-matched healthy controls. Based on gestational age, the periventricular leukomalacia group was stratified into preterm (n = 27) and full-term (n = 15) groups. Voxel-based morphometry was used to analyse whole-brain structural metrics, and motor-related regions were selected as nodes for network construction. Structural covariance analysis was used to quantify the strength of the structural connections between grey matter regions, and graph theory metrics were used to assess network properties. Motor assessments included gross and fine motor skills, and their associations with brain regions were analysed. Both preterm and full-term periventricular leukomalacia groups exhibited abnormal motor networks. Preterm periventricular leukomalacia showed more extensive central grey matter nuclei atrophy, whereas full-term periventricular leukomalacia was predominantly localized to the motor cortex. Children with periventricular leukomalacia displayed decreased connectivity between the central grey matter nuclei and other regions, coupled with increased connectivity between the motor cortex and cerebellar hemispheres. Thalamic volume correlated with gross motor scores in preterm infants. These findings suggest that ischaemic-hypoxic injury disrupts motor grey matter networks, with preterm infants being more severely affected. This study highlights the potential of structural covariance patterns for monitoring brain development and advancing our understanding of aberrant brain development in children with periventricular leukomalacia.