Brain switch for reflex micturition control detected by FMRI in rats

Abstract

The functions of the lower urinary tract are controlled by complex pathways in the brain that act like switching circuits to voluntarily or reflexly shift the activity of various pelvic organs (bladder, urethra, urethral sphincter, and pelvic floor muscles) from urine storage to micturition. In this study, functional magnetic resonance imaging (fMRI) was used to visualize the brain switching circuits controlling reflex micturition in anesthetized rats. The fMRI images confirmed the hypothesis based on previous neuroanatomical and neurophysiological studies that the brain stem switch for reflex micturition control involves both the periaqueductal gray (PAG) and the pontine micturition center (PMC). During storage, the PAG was activated by afferent input from the urinary bladder while the PMC was inactive. When bladder volume increased to the micturition threshold, the switch from storage to micturition was associated with PMC activation and enhanced PAG activity. A complex brain network that may regulate the brain stem micturition switch and control storage and voiding was also identified. Storage was accompanied by activation of the motor cortex, somatosensory cortex, cingulate cortex, retrosplenial cortex, thalamus, putamen, insula, and septal nucleus. On the other hand, micturition was associated with: 1) increased activity of the motor cortex, thalamus, and putamen; 2) a shift in the locus of activity in the cingulate and insula; and 3) the emergence of activity in the hypothalamus, substantia nigra, globus pallidus, hippocampus, and inferior colliculus. Understanding brain control of reflex micturition is important for elucidating the mechanisms underlying neurogenic bladder dysfunctions including frequency, urgency, and incontinence.

Fig. 1.

Functional magnetic resonance imaging (fMRI) experimental protocol for an individual animal. MRI images acquired during each continuous scanning were extracted and averaged according to the different box cars for detecting brain activation during bladder storage or contraction.

Fig. 2.

Blood oxygen level–dependent (BOLD) images showing brain stem activation associated with switching from the bladder storage phase to the bladder contraction phase. The locations of coronal brain sections (A–G) are indicated in the sagittal brain image at the bottom, which correspond to the Bregma coordinates in the anterior–posterior direction as 2.28, 0.24, −1.80, −3.84, −5.88, −7.80, and −9.84 mm. Region of interest (ROI) analysis was performed on the brain stem at coronal sections F and G to detect the activation. The periaqueductal gray (PAG) and pontine micturition center (PMC) are indicated by the blue arrows. The color scale bars indicate the t value.

Fig. 3.

BOLD images showing brain activation associated with switching from the bladder storage phase to the bladder contraction phase. The locations of coronal brain sections (A–G) are indicated in the sagittal brain image at the bottom, which have the same Bregma coordinates as those in Fig. 2. The color scale bars indicate the t value.

Fig. 4.

Region of interest (ROI) analysis of brain regions that did not show enhanced activation in Fig. 3. The 5 brain regions analyzed are marked by arrows. The locations of coronal brain sections (A–G) are the same as those in Fig. 2. Referencing the color scale bar in Fig. 3 left column for the t value.

Fig. 5.

Monocrystalline iron oxide nanoparticle (MION) images showing brain activation during the bladder contraction phase. The locations of coronal brain sections (A–E) are the same as those in Fig. 2. The color scale bar indicate the t value.

Fig. 6.

MRI signal change during the bladder storage phase or during the bladder contraction phase.