Multi-modal MRI Studies In Children With Primary Monosymptomatic Nocturnal Enuresis

Nocturnal enuresis is commonly found in school-age children,with a prevalence rate around 9% in children between 5 and 10 years of age.Nocturnal enuresis occurs during sleep in children who are at least 5 years old,which could persist into adolescence,and has important negative effects on the self-image,psychosocial well-being and emotion of these children.Previous studies have found that there were structural,functional and neurochemical abnormalities in children with nocturnal enuresis.These findings suggested enuresis was not only with a voiding disorder alone,but also with the brain structural and functional abnormalities.Therefore,this study aimed to further explore the neuroimaging characteristics,which would contribute to understanding of pathomechanism and treatment of nocturnal enuresis.Magnetic resonance imaging(MRI)is non-invasive and sensitive to different brain tissues,and it has been used to study enuresis recently.In order to further investigate the brain functional and structural alteration associated with nocturnal enuresis and its effects,we performed multi-model MRI experiments,including the structural MRI,resting-state functional MRI while withholding urine and functional MRI during affective picture task in children with primary monosymptomatic nocturnal enuresis(PMNE),as well as functional MRI with response inhibition,conflict control and affective picture tasks respectively in adults with a history of childhood enuresis.Fifty children with PMNE,35 healthy children,23 adults with a history of childhood enuresis and 22 healthy controls were recruited as volunteers and their MRI data were collected by the Siemens 3T MRI scanner.The structural MRI experiments showed that there were increased gray matter volumes in supplementary motor/ prefrontal areas and decreased cortical gyrification indices in precuneus in children with PMNE compared to healthy controls.These brain regions might be important in the brain-bladder control model or sleep arousal.In the functional MRI analysis under the withholding urine state,we first found the patients showed increased degree centrality in the inferior frontal gyrus,which was a key brain region associated with response inhibition,and increased functional connectivity between the inferior frontal cortex and precuneus.Therefore,combing with the previous neuroimaging studies about enuresis,we supposed that the brain mechanisms underlying PMNE were probably involved in the abnormal development in frontal and precuneus regions.Furthermore,children with PMNE were found increased brain activity in medial prefrontal cortex in response to negative emotion,using functional MRI with the affective picture task.The results may be due to suffering bed-wetting made the patients sensitive to negative emotion and they need more cognitive control to avoid negative feelings.There were few studies exploring whether the adults with a history of childhood enuresis still suffered potential cognitive or emotional problems.We found that the adults who had experienced enuresis were not significantly different from controls when performing response inhibition and conflict control tasks,while showed different neural response to emotional stimuli.The results might indicate they did not suffer from bed-wetting any longer but were still sensitive to negative events and tried hard to suppress their negative emotion processing.In summary,our results showed that children with PMNE exhibited brain structural and functional abnormalities.This study provided strong evidence that the specific regions and brain network associated with nocturnal enuresis may be developmentally delayed or abnormal in children with PMNE.Furthermore,children with PMNE showed abnormal neural responses to emotional stimuli,and even the adults who had experienced nocturnal enuresis during childhood still suffered such problems.