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OBJECTIVES
To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterizing supraspinal activity in response to bladder distention and cold stimulation.

SUBJECTS/PATIENTS AND METHODS
We recruited 24 female participants, 12 with OAB [median age 40 years (interquartile range 32 - 42)] and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms [34 years (28 - 44)], and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging at 3 Tesla scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100mL body-warm (37° C) saline using a MR-compatible and MR-synchronized infusion-drainage device until strong desire to void (HIGH-FILLING / DRAINING) and bladder filling with cold saline (4° C, i.e., COLD). Whole brain and region of interest analyses were conducted using Statistical Parametric Mapping version 12 (SMP12).

RESULTS
Significant between-group differences were found for 3-day bladder diary [i.e. micturition frequency per 24 hours (p<0.001), micturition volume per micturition (p=0.04), and incontinence episodes per 24 hours (p=0.007)], questionnaires [International Consultation on Incontinence Questionnaire-Female LUT symptoms (overall, filling, and incontinence scores, all p<0.001); the Overactive Bladder Questionnaire short form (symptoms and quality of life scores, both p<0.001); the Hospital Anxiety and Depression Scale (anxiety p=0.004 and depression p=0.003 scores)] as well as urodynamic parameters [strong desire to void (p=0.02), maximum cystometric capacity (p=0.007), and presence of detrusor overactivity (p=0.002)]. Age, weight and cognitive function [i.e. Mini-Mental State Exam (p=1.0)] were similar between groups (p>0.05). In OAB patients, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex, and mid-cingulate cortex, and the COLD task elicited activity in the ventrolateral prefrontal cortex, cerebellum, and basal ganglia. Compared to HCs, OAB patients showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and ventrolateral prefrontal cortex during HIGH-DRAINING.

CONCLUSIONS
The current findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lack activity in essential sensory processing areas such as the insula. Instead, accessory areas such as the cerebellum showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent incontinence. The novel findings of this study provide physiologic evidence of the necessity to consider non-bladder etiologies of bladder symptoms.