Degree centrality of key brain regions of attention networks in children with primary nocturnal enuresis: A resting‐state functional magnetic resonance imaging study

Nocturnal enuresis is a common and distressing developmental disease, which may cause various degrees of psychosocial stress and impairment to self-esteem in affected children as well as agitation to their parents or caregivers. Nevertheless, the etiology and pathogenesis of nocturnal enuresis are not understood. Currently, nocturnal enuresis is generally considered a multifactorial disease associated with a complex interaction of somatic, psychosocial, and environmental factors. A variety of postulations have been proposed to explain the occurrence and progression of nocturnal enuresis, including hereditary aberration, abnormal circadian rhythm of antidiuretic hormone secretion during sleep, bladder dysfunction, abnormal sleep, difficulties in arousal, neuropsychological disorders, and maturational delays of the brain. In recent decades, the introduction of functional neuroimaging technologies has provided new approaches for uncovering the mechanisms underlying nocturnal enuresis. The main neuroimaging modalities have included brain morphometry based on structural magnetic resonance imaging (MRI), task-based and event-related functional MRI (fMRI), and resting-state fMRI. The relevant studies have indicated that nocturnal enuresis is associated with functional and structural alterations of the brain. In this review, we briefly summarized the popular hypotheses regarding the pathogenesis of nocturnal enuresis and the current progress of functional neuroimaging studies in examining the underlying mechanisms thereof.

ObjectivePrimary nocturnal enuresis (PNE) is a common developmental condition in school-aged children. The objective is to better understand the pathophysiology of PNE by using insula-centered resting-state functional connectivity (rsFC).MethodsWe recruited 66 right-handed participants in our analysis, 33 with PNE and 33 healthy control (HC) children without enuresis matched for gender and age. Functional and structural MRI data were obtained from all the children. Seed-based rsFC was used to examine differences in insular functional connectivity between the PNE and HC groups. Correlation analyses were carried out to explore the relationship between abnormal insula-centered functional connectivity and clinical characteristics in the PNE group.ResultsCompared with HC children, the children with PNE demonstrated decreased left and right insular rsFC with the right medial superior frontal gyrus (SFG). In addition, the bilateral dorsal anterior insula (dAI) seeds also indicated the reduced rsFC with right medial SFG. Furthermore, the right posterior insula (PI) seed showed the weaker rsFC with the right medial SFG, while the left PI seed displayed the weaker rsFC with the right SFG. No statistically significant correlations were detected between aberrant insular rsFC and clinical variables (e.g., micturition desire awakening, bed-wetting frequency, and bladder volume) in results without global signal regression (GSR) in the PNE group. However, before and after setting age as a covariate, significant and positive correlations between bladder volume and the rsFC of the left dAI with right medial SFG and the rsFC of the right PI with right medial SFG were found in results with GSR in the PNE group.ConclusionTo the best of our knowledge, this study explored the rsFC patterns of the insula in children with PNE for the first time. These results uncovered the abnormal rsFC of the insula with the medial prefrontal cortex without and with GSR in the PNE group, suggesting that dysconnectivity of the salience network (SN)-default mode network (DMN) may involve in the underlying pathophysiology of children with PNE. However, the inconsistent associations between bladder volume and dysconnectivity of the SN-DMN in results without and with GSR need further studies.

We aimed to explore the brain functional connectivity mechanism of attention cognitive impairment in children with nocturnal enuresis (NE). Children with NE often show attention cognitive deficit, but its brain mechanism remains unclear. Most previous studies have only focused on a single brain region, without involving the association among brain regions. In this study, 26 NE and 26 normal children were selected. Functional magnetic resonance imaging (fMRI) and integrated visual and auditory continuous performance test (IVA‐CPT) were performed. The 12 key brain regions of the dorsal attention network (DAN), default mode network (DMN) and ventral attention network (VAN) were selected as areas of interest, and 66 groups of functional connectivity (FC) were analysed among these 12 brain regions. The correlation between FC and IVA‐CPT in the two groups was analysed. The FC values showed that the groups with significant differences between NE and normal children were lFEF‐aMPFC, rFEF‐lIFG, rFEF‐rIPS and lAG‐VFC (P < 0.05), and the FC value of lAG‐VFC was positively correlated with the Full‐Scale Attention Quotient (FAQ). Our results showed that attention deficit in children with NE was associated with all three networks and was relative to the FC among the three attention networks. DAN was the brain network most related to attention cognition in children with NE, and most of the brain regions with abnormal connectivity in NE were related to the prefrontal lobe. The lAG was also an important brain region in attention impairment in NE.