O1041: Morphologic, Microstructural, and Connectomic Correlates of Nocturnal Enuresis in 9 to 10 Years Old

Background: Nocturnal enuresis is characterized by the unintentional urination during the night on more than two occasions/month, which results in distress for both the affected child and their caregivers. In recent years, the underlying mechanisms have been increasingly explored from a neuroscientific perspective. The purpose of our study is to elucidate the neurostructural correlates of nocturnal enuresis in pediatric patients.

Methods: We retrieved clinical and imaging data from the ABCD database (https://abcdstudy.org/). 537 individuals experiencing nocturnal enuresis without symptoms of constipation, daytime incontinence, or encopresis formed our case group. The control group consisted of 488 participants with no history of urinary incontinence, mental health comorbidities, parental drug use, parental mental health issues, or constipation. We excluded subjects with incomplete clinical or imaging data. Using a whole-brain approach, we employed univariate logistic regression analysis to identify neuroimaging metrics associated with nocturnal incontinence, including fractional anisotropy (FA), neurite density (ND), mean- (MD), radial- (RD) and axial diffusivity (AD) of white matter (WM) tracts, cortical region thickness and surface areas from T1-MPRAGE series, and functional network connectivity correlations from resting-state fMRI. We used false discovery rate (FDR) to correct for multiple comparisons and performed a stepwise regression to select relevant covariates, including biological sex, age, handedness, history of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), major depression disorder (MDD), and race. Finally, we constructed a multivariate model with the presence of nocturnal enuresis as the dependent variable and the identified relevant covariates from the previous stepwise regression analysis as independent variables. All analysis were performed in R version 4.2.2.

Results: The ABCD database consists of 11,876 participants with an average age (SD) of 118.94 (7.46) months. The case group had an average age of 120.57 (7.45) months, with 25.61% female, while the control group had an average age of 118.29 (7.22) months, with 52.66%. We found that the covariates of sex, race, and interview age were statistically significant. However, we did not identify a statistically significant relationship between a diagnosis of ODD, MDD, or ADHD with nocturnal incontinence. Individuals with nocturnal incontinence had significantly higher cortical thickness (adjusted p< 0.05) in several brain regions, including the inferior parietal gyrus in both hemispheres, as well as the right isthmus of the cingulate, right precuneus, right rostral middle frontal gyrus, and the pars orbicularis. We also observed significant increased functional connectivity in brain networks, including the auditory, cingulo-opercular, ventral attention, fronto-parietal, and default networks, in those with nocturnal incontinence.

Conclusion: Higher functional connectivity and cortical thickening in the networks and regions responsible for processing emotions and behavior regulation, executive function, tonic alertness, and auditory processing are indicative of nocturnal enuresis. By utilizing multi-modal neuroimaging analysis, we can gain insight into the underlying mechanisms involved in nocturnal enuresis.