Functional magnetic resonance imaging (fMRI) has given way to quantifiable metrics for observing brain activation during specific states, such as functional connectivity (FC). This metric reflects communication networks between multiple regions of the brain that, although not structurally adjacent, collaborate with each other.  which demonstrates how multiple regions that may not be structurally connected interact with each other in time. Our objective is to investigate the characteristic resting state FC (rsFC) between both full and empty bladder states, as well as compare rsFC between healthy men and women. In this study, we report observations from our second 7T study evaluating rsFC of the brain during neural control over full and empty bladder states using a noninvasive, passive bladder filling. However, this study differentiates from the previous by the inclusion of males and females, as well as evaluating how rsFC differ at each bladder state.

Healthy adult men and women (≥ 18 years) with no history of urinary symptoms or neurological diseases were invited to participate in this study. Uroflow was performed, post-void residual (PVR) volume was measured, and those who failed to meet all inclusion and exclusion criteria were excluded. For data collection, each subject was asked to consume 500mL to 750mL of water and empty their bladder. Next, subjects were placed within the 7T MRI. Anatomical and diffusion tensor imaging (DTI) scans  were obtained. An fMRI obtaining brain activation during the empty state was also collected. Participants then remained within the scanner until they felt the urge to void, prompting a functional scan during the full bladder state. rsFC was then obtained from the fMRI scans, different Talairach regions were investigated and areas with a t-value greater than 2.1 were considered statistically significant. Further investigation into gender distinction was performed and FC differences were calculated and reported.

Twenty individuals (10 women and 10 men) participated in the study. One male   participant’s fMRI did not yield usable rsFC data and was therefore excluded from analysis. The mean age of all participants was 27.21 years (22-55), with an average male age of 22.78 (23-33) and female age of 28.9 (22-55). Ethnicity breakdown showed 6 participants of Asian descent (3M, 3F), 1 female African American subject, 11 white subjects (6M, 5F), and 1 Hispanic female subject. Several areas see increased rsFC during full bladder such as the left lenticular nucleus, left uvula, right ventral posteromedial nucleus of the thalamus, and the right mammillary body, while increased rsFC during empty bladder was seen in the left fusiform gyrus, left putamen, and right ventrolateral nucleus of the thalamus (Figure 1). Eight   areas were statistically significant between full and empty bladder states, including the left fusiform gyrus, lenticular nucleus, putamen, uvula, right superior temporal gyrus, ventroposterior medial nucleus of the thalamus, ventrolateral nucleus, and mammary body (Figure 2a). Furthermore, a difference in rsFC between men and women at both bladder states (empty and full) was noted. During the empty bladder state, a statistically significant difference was noted within the right uvula and tubercle with males having a higher rsFC, while during the full bladder state, a significant difference occurred in the right middle temporal gyrus, again depicting males with a higher rsFC value (Figure 2b).

Functional connectivity has proven to be one of the best indicators of how the brain is communicating when “at rest” in various states. In our study, the two time periods of “rest” correlate with either the full or empty bladder state. Utilization of the 7 Tesla MRI has further increased the resolution and data accuracy of fMRI and thus allowed discovery of functionally connected regions within the brain rather than structurally connected. This information will help us further understand the relationships between the working model of the three brain-bladder circuits . We therefore conclude that the 8 regions that were identified as statistically significant between empty and full bladder states represent regions that play a role in supraspinal control of bladder cycle. Further analysis will be required to discover how involved each region is in maintaining continence, potentially leading to new treatments for lower urinary tract symptoms. When comparing women to men, we see a higher rsFC for men during the empty phase with more involvement of the uvula which aids in motion processing, while men also have higher rsFC during the full bladder state within the middle temporal gyrus, commonly associated with memory processing and visual perception. Further investigation into differences in brain functionality between men and women as it relates to continence and micturition could yield significant results as we believe this is the first time those differences in rsFC have been brought to light.

Although these are preliminary results, they hold promise for both better understanding continence and voiding, as well as future trials of pathologic conditions utilizing noninvasive brain-bladder protocol and the 7T MRI scanner to investigate how rsFC in these regions are affected by disease.

Rijk, Mathijs M., et al. “Parcellation of Human Periaqueductal Gray at 7-T fMRI in Full and Empty Bladder State: The Foundation to Study Dynamic Connectivity Changes Related to Lower Urinary Tract Functioning.” Neurourology and Urodynamics, vol. 40, no. 2, 2021, pp. 616–623., https://doi.org/10.1002/nau.24602.

Continence 2S2 (2022) 100467
DOI: 10.1016/j.cont.2022.100467