Disrupted Cerebellar Functional Connectivity and its Association with Bladder Control in Women with Multiple Sclerosis and Voiding Dysfunction

Salazar B1, Colbert K2, Mazeaud C3, Hoffman K4, Bernard J5, Lincoln J6, Khavari R1

Research Type

Clinical

Abstract Category

Imaging

Abstract 99
Imaging
Scientific Podium Short Oral Session 10
Thursday 24th October 2024
10:00 - 10:07
Hall N106
Imaging Multiple Sclerosis Voiding Dysfunction
1. Department of Urology, Houston Methodist Hospital, Houston, TX, USA, 2. Texas A&M College of Medicine, Houston, TX, USA, 3. Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, USA, 4. Department of Urology, Houston Methodist Hospital, Houston, TX, USA and Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, USA, 5. Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, USA and Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, USA, 6. Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX, USA
Presenter
Links

Abstract

Hypothesis / aims of study
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].
Study design, materials and methods
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.
Results
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).
Interpretation of results
Our preliminary data provide the first description of the FC of the cerebellum and its potential implications in neurogenic lower urinary tract dysfunction.
Concluding message
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.
Figure 1 Figure 1 - Cortical connectivity exhibited in a priori ROIs during the micturition cycle in 10 MS women with VD (ROI1 - right posterior lobe; ROI2 - right cerebellum; ROI3 - left tonsil). Red = increased connectivity, Blue = decreased connectivity.
References
  1. 1. Bastide L, Herbaut AG. Cerebellum and micturition: what do we know? A systematic review. Cerebellum Ataxias. 2020 Dec;7(1):9.
  2. 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. 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.
Disclosures
Funding This work was supported in part by NIDDK grant award K23DK118209 and a Houston Methodist Clinician Scientist Award. Clinical Trial Yes Registration Number ClinicalTrials.gov, NCT03574610 RCT No Subjects Human Ethics Committee Houston Methodist Academic Institute, Institutional Review Board. Helsinki Yes Informed Consent Yes
Citation

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

11/12/2024 21:59:46