Cognitive deficits linked to intrinsic timescales and gray matter volume abnormalities in children with Duchenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) is associated with cognitive deficits and neural abnormalities, but the brain’s global functional hierarchy and its interaction with structural changes remain unclear. This study integrated intrinsic neural timescale (INT) and cerebral structural properties to examine relationships among cognitive function, functional hierarchy, and structural integrity in children with DMD. Methods: Thirty-six children with DMD and 30 healthy control children underwent magnetic resonance imaging (MRI), including T1-weighted and resting-state functional magnetic resonance imaging (rs-fMRI).INT and voxel-based morphometry (VBM) analyses were conducted to assess intrinsic timescales and gray matter volume (GMV). The statistical parametric mapping toolkit was utilized for two-sample t-tests with Gaussian random field correction. Statistical significance thresholds were voxel-wise P < 0.001 and cluster-wise P < 0.05. Spearman correlation analysis was further performed to identify associations between cognitive scores and neural abnormalities. Results: Children with DMD exhibited impaired cognitive function, and distinct neurodevelopmental trajectories, characterized by synchronized shorter INT and lower GMV in limbic-sensorimotor networks; widespread GMV atrophy in the visual, default mode, and dorsal attention networks. GMV in multiple regions was positively correlated with working memory and perceptual reasoning scores. Conclusion: These findings suggest that dystrophin deficiency induces synchronized functional-structural deficits and aberrant neurodevelopmental trajectories, offering insights into neurodevelopmental abnormalities in children with DMD. The integration of INT and GMV provides a novel framework for decoding hierarchical network dysfunction and morphological plasticity changes in DMD, identifying potential targets for cognitive intervention.