Task-based functional fMRI (fMRI) studies have been long utilized to evaluate the central control of bladder perception in response to repetitive bladder filling. This modality may provide a way to phenotype patients with overactive bladder (OAB) and has a potential to assess therapeutic response. Unfortunately, available data have underlined the lack of reliability and repeatability of this method [1]. It should be noted that most of the studies used a block design consisting of discrete epochs of on-off tasks. As bladder perception is immensely subjective, the combination of bladder filling and a participant-indicated desire to void event might be a better paradigm. Hence, we aim to design a sensation-driven fMRI study and evaluate brain activation following the paradigm.

Seventeen healthy female subjects aged 22 – 58 years (mean= 32.53 ± 11.75) were included. The study was performed with approval by the institutional ethical committee and written informed consent by the participants. Prior to the MRI session, all subjects underwent a baseline urodynamic study, and the catheters were subsequently maintained. Imaging was performed on a 3 Tesla Philips Achieva dStream scanner with a 32-channel head coil. MRI session included an anatomical T1-weighted (3D-TFE, TR= 9.7 ms, TE= 4.6 ms, flip angle= 8, isotropic acquisition voxel size= 1 mm) image, task-based functional MRI acquisition (EPI, TE= 30 ms, TR= 2000 ms, FOV= 220x220x158 mm, acquisition voxel size= 2.3x2.3x3.6 mm, matrix= 96x94x44 slices, sense-factor= 2, multiband-factor= 2) and reversed-phase encoded images. 

Each fMRI session lasted 8.5 minutes and was repeated 2-4 times (mean= 3 times) depending on the subjects’ coping ability with the task. The paradigm consisted of repetitive bladder filling (60ml/minute) until first desire (FD) and strong desire (SD) to void was indicated by the subjects, followed by a plateau (5 seconds) and withdrawal of 30 seconds. To prevent constant engagement of the viscerosensory cortex and to obtain baseline data for motor-related brain activity, a diversion visuomotor task was presented randomly to the in-bore-screen. In this task, subjects were instructed to respond with the button press each time the fixation cross changed into “x”. All responses were recorded with Psychopy and further incorporated in data analysis. MRI preprocessing was done with fMRIPrep pipeline (version 20.2.6), including head motion correction and realignment, co-registration and normalization to the standardized Montreal Neurological Institute (MNI) atlas [2]. Six head motion parameters estimated from this step were thereafter incorporated as regressors on the subsequent analysis. SPM12 was used to smooth the data with a 6-mm Gaussian filter and to analyse the data [3]. A General Linear Model was used to model the data of FD, SD and distraction tasks as events, and to evaluate main effects of events as well as interaction effects. Second-level random effect analysis was then performed for the aforementioned event-contrasts and significance was set to cluster level P < 0.05 false discovery rate (FDR) correction.

On average, subjects indicated the FD to void 4.11 times and SD to void 4.24 times. The distraction task was responded to on average 21.43 times. Figure 1 depicts the fMRI Blood Oxygen Level-Dependent (BOLD) activation during FD and SD to void. This area included insula, thalamus, cerebellum, the supplementary motor area, and the frontal gyri. Periaqueductal gray (PAG) and pontine micturition centre (PMC) were also significantly activated during FD and SD to void using the uncorrected p-value, although only activation in the PAG (MNI coordinate: x= -6, y=-34, z =-8) during SD to void that survived the corrected p-value for multiple comparisons.

Here we can observe several brain regions that were significantly activated based on the indicated sensations during repetitive bladder filling tasks. Activation of these regions were consistent with data from the literature. Interestingly, it seems that there is a robust relation between signal intensity and urge intensity. As we can see in figure 1, fMRI BOLD activation during the SD to void appeared to be stronger compared to during the FD to void. The activation in the brainstem regions limitedly survived the multiple comparisons most likely due to the small size of these structures.

In this study, we have designed a robust sensation-driven fMRI paradigm which enables evaluation of bladder proprioception during FD and SD to void. To our knowledge, we are among the first who demonstrate the relation between signal intensity of the brain and the urge intensity. The next step is to validate this paradigm in patients with OAB.

Clarkson BD, Tyagi S, Griffiths DJ, et al. Test-retest repeatability of patterns of brain activation provoked by bladder filling. Neurourol Urodyn. 2017;36(6):1472-1478.
Esteban O, Markiewicz CJ, Blair RW, et al. fMRIPrep: a robust preprocessing pipeline for functional MRI. Nat Methods. 2019;16(1):111-116.
Friston K, Holmes A, Worsley K, et al. Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp. 1995;2:189-210.

Continence 7S1 (2023) 100755
DOI: 10.1016/j.cont.2023.100755