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

Purpose Existing literature strongly supports the idea that children with primary nocturnal enuresis (PNE) have a delayed brainstem maturation. However, the connection between pre-micturition arousal responses and brain functional connectivities is still not clearly defined. In light of this gap, 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. Materials and methods Extensive 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. The analysis incorporated data from 133 patients, each diagnosed with PNE and demonstrating varied levels of MDA functionality, alongside data from 40 healthy children, characterized by optimal MDA function. Neuroimaging data, derived from functional magnetic resonance imaging (fMRI), were subjected to correlational analyses with behavioral data that were obtained through precise clinical observations. Results 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. However, no significant correlations were detected in other subregions of the PAG in this study. Conclusions Aberrant RSFC between the PAG, particularly the vlPAG and dmPAG subregions, and critical nodes within the dorsal and ventral attention networks, as well as the default mode network, in association with MDA dysfunction, elucidates the neural substrates underpinning the symptomatology of PNE. This revelation underscores potential neural targets for future therapeutic interventions.