Purpose: Assessing brainstem function in humans through typical neuroimaging modalities has been challenging. Our objective was to evaluate brain and brainstem activation patterns during initiation of voiding in healthy males and females utilizing a 7 Tesla magnetic resonance imaging (MRI) scanner and a noninvasive brain-bladder functional MRI (fMRI) protocol. Methods: Twenty healthy adult volunteers (10 males and 10 females) with no history of urinary symptoms were recruited. Each volunteer underwent a clinic uroflow and postvoid residual assessment and was asked to consume water prior to entering the scanner. Anatomical and diffusion tensor images were obtained first, followed by a blood oxygenation level dependent (BOLD) resting-state fMRI (rs-fMRI) during the empty bladder. Subjects indicated when they felt the urge to void, and a full bladder rs-fMRI was obtained. Once completed, the subjects began 5 voiding cycles, where the first 7.5 seconds of each voiding cycle was identified as “initiation of voiding.” BOLD activation maps were generated, and regions of interests with a t-value greater than 2.1 were deemed statistically significant. Results: We present 5 distinct regions within the periaqueductal gray (PAG) and pontine micturition center (PMC) with statistically significant activation associated with an initiation of voiding in both men and women, 3 within the PAG and 2 within the PMC. Several additional areas in the brain also demonstrated activation as well. When comparing males to females, there was an overall lower BOLD activation seen in females throughout all regions, with the exception of the caudate lobe. Conclusions Our study effectively defines regions within the PAG and PMC involved in initiation of voiding in healthy volunteers. To our knowledge, this is the first study investigating differences between male and female brainstem activation utilizing an ultra-high definition 7T MRI.

PURPOSE: To simultaneously monitor electrical discharges in various bladder regions and the external urethral sphincter (EUS) during voiding contractions, and to assess the functional role of myogenic modulation of the lower urinary tract (LUT) by ionotropic purinergic receptors containing the P2X3 subunit. METHODS: Female Sprague-Dawley rats were anesthetized with urethane, and implanted with a suprapubic catheter for open cystometry. Flexible microelectrodes were placed ventrally in the bladder dome, upper bladder, lower bladder, and bladder base, along with the middle section of the exposed EUS. Intravesical P2X3-containing receptors were blocked with AF-323, a specific P2X3-P2X2/3 receptor antagonist. A digital electrophysiology amplifier was used to record electrical and cystometric signals throughout the LUT. RESULTS: Electrical activity in the LUT started before effective voiding contractions. Bladder pressure and electrical waveforms showed consistent out-of-phase activity when compared with the recordings made at the EUS. This pattern was also observed during voiding contractions in the presence of AF-353, supporting the hypothesis that during bladder distension, activation of P2X3-containing receptors is required for voiding contractions. Furthermore, the inhibition of P2X3-containing receptors significantly decreased the amplitude of electrical signals in the urinary bladder, but not the base or EUS. CONCLUSIONS: Our results provide novel information about the regulation of the micturition process by P2X3-containing receptors located in the inner layers of the bladder.
Animals ; Catheters ; Electrophysiology ; Female* ; Humans ; Lower Urinary Tract Symptoms ; Microelectrodes ; Purinergic P2X Receptor Antagonists ; Rats* ; Rats, Sprague-Dawley ; Receptors, Purinergic ; Urethane ; Urethra ; Urinary Bladder* ; Urinary Tract ; Urination*