Abstract Periventricular leukomalacia is a common neuroimaging finding in patients with spastic cerebral palsy. Myelin damage disrupts neuronal connectivity. However, specific alterations in the gray 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 gray matter network alterations following early white matter injury in infants and young children. High-resolution T1-weighted 3T 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 analyze 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 gray 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 analyzed. Both preterm and full-term periventricular leukomalacia groups exhibited abnormal motor networks. Preterm periventricular leukomalacia showed more extensive central gray 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 gray 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 ischemic-hypoxic injury disrupts motor gray 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.
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