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Altered Periaqueductal Gray Functional Connectivity in Overactive Bladder Patients: A Resting-State Functional Magnetic Resonance Imaging Study Using Clustering Analysis

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Purpose: Overactive bladder (OAB) syndrome is a subset of storage lower urinary tract symptoms that significantly affects health-related quality of life, impacting social, occupational, and psychological well-being. Although the precise pathophysiology of OAB remains unclear, disruption of the neural network that regulates lower urinary tract activity has been suggested. The brain-bladder axis depends on a complex and extensive network of brain regions, with the periaqueductal gray (PAG) playing a pivotal role in mediating bidirectional communication. Methods: This study investigates whether the functional connectivity-based organization of the PAG in human subjects changes dynamically over time. OAB patients and healthy controls (HC) underwent resting-state functional magnetic resonance imaging at 7 T, beginning with an empty bladder (subsensory threshold bladder filling state). Functional connectivitybased clustering analysis was performed to evaluate time-dependent changes in PAG organization. Results: Significant group differences in time-dependent PAG functional organization were observed (P=0.017). In HC, functional subdivisions of the PAG reorganized dynamically during the resting-state scan, whereas OAB patients displayed a largely static functional organization, showing minimal change over time. Conclusions: These findings indicate altered PAG signaling and differences in sensory processing among OAB patients. The absence of dynamic PAG reorganization may contribute to OAB pathophysiology, offering new insight into its neural mechanisms.

Abstract

Purpose: Overactive bladder (OAB) syndrome is a subset of storage lower urinary tract symptoms that significantly affects health-related quality of life, impacting social, occupational, and psychological well-being. Although the precise pathophysiology of OAB remains unclear, disruption of the neural network that regulates lower urinary tract activity has been suggested. The brain-bladder axis depends on a complex and extensive network of brain regions, with the periaqueductal gray (PAG) playing a pivotal role in mediating bidirectional communication. Methods: This study investigates whether the functional connectivity-based organization of the PAG in human subjects changes dynamically over time. OAB patients and healthy controls (HC) underwent resting-state functional magnetic resonance imaging at 7 T, beginning with an empty bladder (subsensory threshold bladder filling state). Functional connectivitybased clustering analysis was performed to evaluate time-dependent changes in PAG organization. Results: Significant group differences in time-dependent PAG functional organization were observed (P=0.017). In HC, functional subdivisions of the PAG reorganized dynamically during the resting-state scan, whereas OAB patients displayed a largely static functional organization, showing minimal change over time. Conclusions: These findings indicate altered PAG signaling and differences in sensory processing among OAB patients. The absence of dynamic PAG reorganization may contribute to OAB pathophysiology, offering new insight into its neural mechanisms.

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