Fig 1.
Statistical analysis of cystometrogram and visceromotor reflex (VMR +/- standard error) recordings during bladder infusion.
Shown are the tracings of (A) cystometrogram, (B) IVPmax (maximum intravesical pressure), (C) bladder capacity, (D) pressure threshold to first void/leak, (E) VMR threshold, and (F) VMR threshold/IVPmax for WAS and control animals. * indicated when voiding happened. The bar on the vertical axis of Figure (A) is a calibration bar, whose length represents a bladder pressure of 40 cmH2O.
Fig 2.
(A) Representative examples of visceromotor reflex (VMR) in the control and WAS animals at each level of bladder pressure between 0 and 40 cmH2O. (B) During isotonic bladder distension, VMR AUC (VMR +/- standard error) in WAS significantly increased compared to controls at 20 cmH2O (P = 0.03). VMR: visceromotor reflex. AUC: area under the curve. Note different scales used at different pressure levels. WAS: water avoidance stress.
Fig 3.
Differences in functional brain activation during bladder filling of WAS rats compared to controls.
Left column: Statistical parametric maps showing significant difference (P < 0.05 for clusters of greater than 100 contiguous significant voxels) in brain activation in sedated WAS rats compared to controls are superimposed on gray-scale coronal sections showing the rCBF distribution of the template brain. Right column: ROI analysis shows group mean rCBF (± S.E.) for select brain regions in the micturition circuit, in which rCBF in each animal was normalized by its whole brain mean perfusion. * P < 0.05, **P < 0.005 for clusters of greater than 100 significant, contiguous voxels. Abbreviations: Cx (cortex), PAG (periaqueductal gray), PB (parabrachial nucleus).
Fig 4.
Detailed view of functional brain activation during bladder filling of WAS rats compared to controls at the level of the pontine micturition center (9.1 and 9.4 mm posterior to bregma).
Significant differences in regional CBF during bladder filling of WAS rats compared to controls (red indicates increased rCBF, blue indicates decreased rCBF). Also shown are the region-of-interest definition (green) for the Barrington nucleus (BN) and parabrachial nucleus (PBN) used in our analyses, as well as the landmark for the dorsal tegmentum (DTg).
Fig 5.
Summary of the significant changes in regional cerebral blood flow (rCBF) of WAS vs. control rats during passive bladder filling as related to a simplified model of the micturition circuit.
Data are summarized from the SPM analysis shown in Fig 3, with red indicating significant increases in rCBF and blue indicating significant decreases in rCBF. Abbreviations: Cx (cortex), HPC (hippocampus), lPFC (lateral prefrontal cortex), mPFC (medial prefrontal cortex), PAG (periaqueductal gray), PMC (pontine micturition center, parabrachial/Barrington nucleus complex), rCBF (regional cerebral blood flow). Adapted from Griffiths [36] and DeGroat and Yoshimura [37].
Fig 6.
Seed correlation of functional activity across the whole brain during bladder filling.
WAS compared to control rats show greater functional connectivity of (row 1) the posterior cingulate to the parabrachial/Barrington nucleus complex, (row 2) the posterior insula to anterior secondary motor cortex (M2), and (row 3) the Barrington nucleus to the anterior, dorsal midline thalamus (mediodorsal, MD; paraventricular, PVN), as well as the ventrobasilar thalamic complex, primary and secondary somatosensory cortex (S1, S2) and retrosplenial cortex.