Hypothesis: Whole brain functional connectivity patterns become less predictable with worsening severity of overactive bladder (OAB) syndrome.
 
Aim: This is the first study to examine the relationship between clinical measures of idiopathic OAB and resting state functional connectivity in female patients with an empty bladder.

This is an analysis of cross-sectional preliminary data from females age ≥ 50 years with idiopathic OAB who were invited to participate in an ongoing randomized controlled trial. Women with neurologic disorders, cognitive impairment screen positive on the Montreal Cognitive Assessment, post-void residual volume > 200 mL, or pelvic floor physical therapy or oral medications for OAB in the last six months were excluded. Eligible subjects completed the Overactive Bladder Questionnaire (OABq), Patient Perception of Bladder Condition (PPBC). Patient Health Questionnaire (PHQ-9) and Hamilton Anxiety Measurement (HAM-A) to assess states of depression and anxiety, respectively. In all the questionnaires, a higher score indicates greater severity of the condition. Baseline characteristics were collected, and a score was calculated for Anticholinergic Cognitive Burden (ACB) from review of current medications. 
 
After spontaneously voiding, participants completed the fMRI protocol [1] using 3.0 T Vida full body MRI scanner with a standard 20-channel head coil. Three dimensional structural images were obtained from a T1-weighted sequence; (0.86 x 0.86 x 1.00 mm3 resolution). Resting state fMRI (Rs-fMRI) data were collected over six minutes while participants were instructed to focus on a white cross with a black background. Individual fMRI activation maps were generated during the Rs-fMRI. Resting state functional connectivity (rsFC) patterns of these regions were calculated and compared. Similarity of the FC pattern from one subject relative to the others in the group was expressed by a parameter FC_Sim [2]. Higher FC_Sim values indicate higher similarity to the group. Pearson correlation coefficients were calculated for FC_Sim values and clinical measures with significance at p value < 0.05. Missing values for clinical variables were not imputed.

fMRI and clinical data was available for twelve women. FC_Sim values ranged from 3.18 to 5.57, with mean (SD) of 4.54 (0.68). Participant characteristics and correlation coefficients for clinical variables with FC_Sim can be found in the Table. Significant inverse correlation was found for FC_Sim with number of daily leakage episodes on the bladder diary R -0.65, p=0.03 and with depression scores R -0.65, p=0.03, see the Figure. Age, BMI, ACB score, HAM-A score, OABq scores, PPBC scores, and the number of voids and urgency episodes on the bladder diary did not correlate with FC_Sim.

Greater severity of daily urine leakage episodes and severity of depressive symptoms correlate with less similar rsFC. Less similar brain rsFC patterns may be markers of more severe disease state. Similarity of rsFC did not significantly correlate with patient reported severity of OAB symptoms or voiding diary measures of urgency episodes and number of voids.

This analysis of resting state brain functional connectivity similarity suggests in women with less severe urinary leakage and depression, connectivity patterns are similar. In women with more severe disease, connectivity patterns diverge and are less similar. Less predictable brain rsFC patterns may be a marker of more severe disease states reflected by worse urinary leakage and depressive symptoms.

High, R. A., Danford J. M., Shi, Z., Karmonik, C., Kuehl, T. J., Bird, E. T., Khavari, R. (2020). Protocol for a multicenter randomized, double blind, controlled pilot trial of higher neural function in overactive bladder patients after anticholinergic, beta-3 adrenergic agonist, or placebo. Contemporary Clinical Trials Communications, 19 (2020) 100621
Khavari, R., Elias, S. N., Boone, T., & Karmonik, C. (2019). Similarity of functional connectivity patterns in patients with multiple sclerosis who void spontaneously versus patients with voiding dysfunction. Neurourology and urodynamics, 38(1), 239–247.