Although the cerebellum is frequently excluded from traditional micturition network models, there is increasing evidence that it plays a vital role in regulating lower urinary tract function [1]. Our team has identified three regions of interest (ROIs) and demonstrated significant functional connectivity (FC) between these cerebellar areas and other brain regions in healthy men and women [2]. This study focuses on examining how this connectivity is influenced by demyelinating conditions such as Multiple Sclerosis (MS). To achieve this, we utilized a state-of-the-art high-resolution 7 Tesla MRI scanner in conjunction with a urodynamic (UDS) protocol [3].

Adult women diagnosed with MS and voiding dysfunction (VD) were recruited for this study (n=10) with an age range of 35-77 years (mean age 53.4). VD was defined by a post-void residual/bladder capacity ratio ≥40%, a Liverpool Nomogram percentile below 10%, or reliance on self-catheterization. Prior to undergoing neuroimaging, participants were instructed to completely empty their bladder. Subsequent to the acquisition of initial anatomical images, functional MRI (fMRI) scans were performed while the bladder was filled with warm sterile saline infused at a rate of 75 ml/minute via an MRI-compatible UDS catheter. During the fMRI session, participants were prompted to signal when they experienced a strong urge to void. They were then instructed to hold for 30 seconds and attempt to void. If unsuccessful, the bladder was manually aspirated, and the cycle was repeated a total of four times.

For FC analysis, the data were pre-processed using the CONN toolbox in MATLAB, which incorporates the statistical parametric mapping (SPM) toolbox. Blood oxygen level-dependent (BOLD) signal contrast maps were generated, and seed-to-voxel analysis was conducted using predetermined ROIs. Nonparametric statistics were applied, with a voxel threshold set at p<0.05 based on the Threshold Free Cluster Enhancement method.

Our lab previously demonstrated that three spherical ROIs with a radius of 2 mm (in the right lobule V, in the right crus I, and in the left crus I) exhibit significant FC with the cuneal and supracalcarine cortex, and to a lesser extent, the precuneus in healthy individuals [2]. In this study, we further characterized the involvement of these ROIs in the micturition network and investigated their alterations in ten women with MS and VD.

In our current analysis, we observed distinct FC patterns in women with MS and voiding dysfunction compared to healthy controls. Specifically, there was reduced cortical connectivity originating from the right posterior lobe (ROI1) and increased connectivity from the right cerebellum (ROI2) in MS patients. Furthermore, in healthy controls, we identified an inhibitory effect of the left tonsil (ROI3) on the right cerebellar crus. In contrast, in MS patients with voiding dysfunction, this inhibitory effect was absent, accompanied by connectivity in the right cerebellum and cortex (Fig. 1).

Our preliminary data provide the first description of the FC of the cerebellum and its potential implications in neurogenic lower urinary tract dysfunction.

By deepening our comprehension of the brain-bladder network in both healthy individuals and those with neurological conditions, we can pave the way for the development of more precise therapeutic interventions in the future.

1.	Bastide L, Herbaut AG. Cerebellum and micturition: what do we know? A systematic review. Cerebellum Ataxias. 2020 Dec;7(1):9.
2.	Mazeaud C, Bernard J, Salazar BH, Su J, Karmonik C, Khavari R. The role of the cerebellum in the functional connectivity of the lower urinary tracts in the healthy patient: a 7 Tesla study. Under review at Neurourol Urodyn.
3.	Kuhtz-Buschbeck JP, Gilster R, van der Horst C, Hamann M, Wolff S, Jansen O. Control of bladder sensations: An fMRI study of brain activity and effective connectivity. NeuroImage. 2009 Aug;47(1):18–27.

Continence 12S (2024) 101441
DOI: 10.1016/j.cont.2024.101441