Brain microstructure in children with primary monosymptomatic nocturnal enuresis: a diffusion kurtosis imaging study

The microstructural differences in the brain associated with primary monosymptomatic nocturnal enuresis (PMNE) are not well understood. In particular, the relationship between these differences and micturition desire-awakening (MDA) dysfunction, the central pathophysiological mechanism of PMNE, remains unexplored. Diffusion kurtosis imaging (DKI) offers detailed insight into microstructural complexity and may capture developmental variation in children with PMNE. In this study, DKI was used to assess 26 children with PMNE and 26 age- and sex-matched healthy controls. A two-sample t-test was performed to compare DKI metrics across the brain with AlphaSim correction for multiple comparisons. Correlation analysis between DKI indices and MDA functional grade scores was also conducted using Spearman's rank correlation and Bonferroni correction. Children with PMNE exhibited microstructural differences in several brain regions, mainly within the executive control network, dorsal attention network, ventral attention network, sensorimotor network, salience network, default mode network (DMN), visual network (VN), and cerebellum. MDA dysfunction was negatively correlated with radial kurtosis (RK) in the right cerebellum crus I and positively correlated with mean kurtosis (MK) in DMN and VN regions, as well as axial kurtosis (AK) and RK in DMN regions.

The findings suggest that PMNE is associated with developmental variations in multiple neural networks. Several of these microstructural differences are directly linked to MDA dysfunction, potentially contributing to our understanding of the neurodevelopmental basis of PMNE. Given the absence of large-scale normative pediatric DKI reference datasets, these microstructural differences might also be developmental variations.

• PMNE is primarily attributed to MDA dysfunction (the inability to awaken to bladder fullness), alongside factors like reduced nocturnal antidiuretic hormone secretion and decreased bladder capacity. • Previous structural and functional MRI studies have identified variations in key brain regions in children with PMNE, including the attention networks, thalamus, cerebellum, salience network (SN), sensorimotor network (SMN) and default mode network (DMN).

• This study provides the first application of DKI in PMNE, revealing widespread network-level microstructural differences across the attention networks, SMN, SN, DMN, visual network, and cerebellum. • DKI metrics correlate with MDA dysfunction severity, linking microstructural variation to the core arousal mechanism.