Supraspinal network activity related to lower urinary tract (LUT) function has commonly been investigated using functional magnetic resonance imaging (fMRI) during catheter-based invasive bladder filling.[1] However, catheterization and the fast unnatural rate of bladder filling, along with lower than body temperature liquid, may cause inconvenience and affect afferent signaling.[2] Previously, the use of oral hydration to achieve the natural physiologic full-bladder state during fMRI has successfully elicited functional connectivity of regions in the LUT control network.[3] Accordingly, we hypothesized that resting-state functional connectivity (rsFC) acquired during a natural oral hydration protocol would differentiate between empty bladder (no desire to void) and full bladder (strong desire to void) states in adults with overactive bladder (OAB). The aim was to identify state-dependent (full versus empty bladder) supraspinal connectivity patterns using neuroimaging-based assessment of brain-derived signals, patient-reported urgency/bladder fullness, and non-invasive measures of bladder volume.

Male and female adults with idiopathic OAB, excluding voiding dysfunction (postvoid residual [PVR] > 200 mL), bladder outlet obstruction, and neurogenic disorders, underwent a natural bladder filling protocol during 3.0 Tesla fMRI. Subjects were familiarized with a 10-point Likert scale, which assessed bladder fullness (1= no desire to void, 10= very strong desire to void). After consuming 500 mL of water, participants voided immediately, after which PVR and baseline urgency rating were measured. Participants underwent anatomical scans followed by rsFC assessment (rsFC-full bladder), and another set of urgency ratings was acquired. Participants then exited the scanner to void, PVR was measured, and they returned to the scanner for empty bladder rsFC scans (rsFC-empty bladder). All anatomical and functional scans were 6 minutes 23 seconds long, and bladder volume was defined as PVR + voided volume in mL.

Preprocessing of fMRI included motion correction, denoising, co-registration, and normalization. 19 bladder control-related regions of interest (ROIs) were identified from previous work[3] and ROI-to-ROI functional connectivity analyses were performed using CONN and SPM. Second-level analyses employed a paired general linear model comparing full versus empty bladder states. Statistical significance was determined using false discovery rate (FDR) correction for multiple comparisons across ROI–ROI connections.

Thirteen adults (mean age 67 years) completed the natural bladder filling protocol. Urgency ratings were higher during rsFC-full bladder than rsFC-empty bladder (mean 8.5 vs mean 2.0). Bladder volumes were on average 407 mL (mean PVR 92 mL) during rsFC-full bladder. 

ROI-to-ROI functional connectivity analysis revealed a single significant cluster of 3 ROIs (two within Supplementary Motor Area [SMA] and one within Medial Frontal Gyrus [MFG]) differentiating full from empty bladder states (FDR-corrected p = 0.025). Connectivity within the SMA ROIs and between SMA and MFG increased during full bladder. No other clusters or ROI-ROI connections survived multiple comparisons correction.

This natural bladder filling protocol elicits measurable and state-dependent changes in supraspinal functional connectivity in individuals with OAB. Increased SMA–MFG coupling during strong desire to void supports the role of motor–prefrontal circuits in sensation-to-action integration during LUT state transitions. This well-tolerated oral hydration paradigm preserves physiological bladder filling confirmed by non-invasive measures of bladder fullness: qualitative (patient perceived) and quantitative (bladder volumes).

Resting-state functional connectivity acquired during a non-invasive natural filling protocol differentiates empty and full bladder states in OAB. This approach provides a physiologically relevant framework for investigating supraspinal mechanisms of bladder sensation and may inform future biomarker development and therapeutic targeting.

M. Walter et al., “Reliability of supraspinal correlates to lower urinary tract stimulation in healthy participants–a fMRI study,” Neuroimage, vol. 191, pp. 481–492, 2019.
I. Mawla et al., “Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP Network Neuroimaging Study,” Scientific reports, vol. 10, no. 1, p. 19901, 2020.
A. Bayer, K. Hoffman, B. Salazar, B. Aazhang, and R. Khavari, “A deeper exploration of functional connectivity of brain regions regulating bladder function in healthy adults,” Continence, p. 101897, 2025.

Continence 19S (2026) 102670
DOI: 10.1016/j.cont.2026.102670