Hypothesis / aims of study
Urine storage is a complex physiologic process that is under central nervous system control. While the micturition pathway has been studied through various functional brain imaging studies, thereby providing insight on important brain regions and their role in voiding, how brain activity changes as bladder volume and bladder sensations change remains unclear. In this study, we aimed to quantify cerebral perfusion and the change in brain activity in healthy subjects during bladder filling.
Study design, materials and methods
Healthy women without overactive bladder were recruited to undergo blood oxygen level dependent (BOLD) and arterial Spin Labeling functional neuroimaging (ASL fMRI), which is a newer functional neuroimaging technique that allows measurement of cerebral perfusion/oxygen consumption. Bladder filling was performed by infusing saline into the bladder at a rate of 50ml/minute via foley catheter. Subjects were provided with a response button to signal to the investigators their experiences of first sensation of bladder filling, first desire to void, and strong desire to void as they occurred during bladder filling. Scans were performed at bladder volumes of 0ml, 50ml, 100ml, 200ml, 350ml, and 500ml.
Eight healthy female participants were recruited. On average, participants experienced first and strong desire to void after 112 and 284mL bladder filling, respectively. Tables 1 and 2 show normalized CBF and absolute transverse relaxation rates respectively, during baseline, first desire to void and strong desire to void states for the selected regions of interest. The insula and right anterior cingulate cortex (ACC) exhibited significantly increased perfusion at first desire to void when compared to baseline while the supplemental motor cortex (SMC) exhibited decreased perfusion for the same comparison. Significantly decreased perfusion was observed in the insula, left hippocampus, and right posterior cingulate cortex (PCC) at strong desire to void when compared to first desire to void. The SMC and right dorsolateral pre-frontal cortex (DLPFC) exhibited significantly decreased transverse relaxation rates at first desire to void when compared to baseline while the right thalamus exhibited significantly increased rates for the same comparison. There were no significant differences in transverse relaxation rates at a strong desire to void when compared to first desire to void.
Interpretation of results
Functional neuroimaging has proved to be a particularly useful tool for studying how the central nervous system processes the desire to void and micturition. Recently, a meta-analysis of neuroimaging studies was conducted to determine the most likely brain regions involved in urine storage. This study identified 14 neuroimaging studies and 89 foci of brain activity that were previously reported to be involved during urine storage. When the neuroimaging data was synthesized, the following regions were identified and considered to be the most likely sites involved during bladder filling: thalamus, insula, pons, brainstem and cerebellum. During urine storage, afferent signaling from the bladder provides information on the fullness of the bladder. These signals are relayed to the periaqueductal gray (PAG) which communicates with numerous higher order brain structures including the insula, the anterior cingulate cortex, the pons, the thalamus, and the prefrontal cortex to coordinate bladder filling, provide conscious sensation of filling, and suppress voiding until appropriate.
To our knowledge, this is the first study using fMRI that evaluates brain activity at discrete levels of bladder filling in normal subjects. Previous fMRI studies have observed similar increased brain activation during bladder filling in similar regions. These results support the hypothesis that suppression of a strong desire to void results in deactivation of the regions previously activated by the first desire to void. This study lays the foundation for investigating the potential difference in responses in patients with overactive bladder (OAB), which could provide insight into the neurological mechanisms involved in OAB.
Our study has many limitations including the potential for differences in brain activity in men and women as this study only includes female patients. However, other work has suggested that there are no significant differences in brain activation between genders. Additionally, non-physiologic bladder filling via catheter may not accurately represent brain activation seen in normal bladder filling. Finally, this study evaluates the changes seen at specifically chosen regions of interest, and may overlook other important areas involved in bladder filling.