Periaqueductal gray subregions connectivity and its association with micturition desire-awakening function

Existing literature strongly supports the idea that children with primary nocturnal enuresis (PNE) have brainstem abnormalities. However, the connection between pre-micturition arousal responses and brain functional connectivities is still not clearly defined. Our study investigated the correlation between the gradations of micturition desire-awakening (MDA) functionality and the functional connectivity of the midbrain periaqueductal gray (PAG), a pivotal brainstem hub implicated in the neural regulation of micturition in humans. Neuroimaging and behavioral data from 133 patients with PNE and 40 healthy children were acquired from functional magnetic resonance imaging (fMRI) and precise clinical observations, respectively. The whole-brain correlation analyses were undertaken to elucidate the complex connectivity patterns between the subregions of PAG and the cerebral cortex, with a focus on their correlation to the spectrum of MDA functionality. A positive correlation was identified between MDA dysfunction and the resting-state functional connectivity (RSFC) between the left ventrolateral periaqueductal gray (vlPAG) and the right temporal pole of the superior temporal gyrus. Conversely, a negative correlation was observed between MDA dysfunction and the RSFC of the right vlPAG with the right superior parietal lobule. Additionally, MDA dysfunction exhibited a negative association with the RSFC between the dorsomedial PAG (dmPAG) and the right inferior parietal lobule. These findings may indicate that the specific signal from a distended bladder is blocked in the PAG and its functional connectivity with the executive function, attention, and default mode networks, ultimately leading to impaired arousal and bladder control. This revelation underscores potential neural targets for future therapeutic interventions.