Brain activity underlying impaired continence control in older women with overactive bladder

Abstract

Aims: To identify, in subjects with overactive bladder (OAB), differences in brain activity between those who maintained and those who lost bladder control during functional magnetic resonance imaging (fMRI) of the brain with simultaneous urodynamics.

Methods: Secondary analysis of a cohort of older women (aged >60) with proven urgency urinary incontinence, who, in the scanner, either developed detrusor overactivity and incontinence (the "DO group") or did not (the "no DO" group). A priori hypothesis: during urgency provoked by bladder filling, without DO, activity in regions related to continence control is diminished in the DO group; specifically (1a) less activation in supplementary motor area (SMA) and (1b) less deactivation in prefrontal cortex (PFC) and parahippocampal complex (PH). We also explored phenotypic (clinical and urodynamic) differences between the groups.

Results: During urgency preceding DO, the DO group showed stronger activation in SMA and adjacent regions (hypothesis 1a rejected), and less deactivation in PH but no significant difference in PFC (hypothesis 1b partially accepted). These subjects were older, with more changes in brain's white matter, decreased tolerance of bladder filling and greater burden of incontinence.

Conclusions: (1) In older women with OAB, brain activity in the SMA is greater among those with more easily elicitable DO, suggesting a compensatory response to failure of control elsewhere. (2) OAB is heterogeneous; one possible phenotype shows severe functional impairment attributable partly to age-related white matter changes. (3) Functional brain imaging coupled with urodynamics may provide CNS markers of impaired continence control in subjects with OAB.

Copyright © 2012 Wiley Periodicals, Inc.

Figures

Figure 1

Provisional working model of brain/bladder control,,,,,. Voiding is triggered and coordinated by the voiding reflex shown in simplified form at the bottom of the diagram. Cerebral control is exercised by suppressing the reflex at the PAG during storage, and lifting suppression for voiding. Normal continence mechanism: ascending signals pass from the PAG via the thalamus to the insula, where desire to void is registered. Signals are relayed to excite the inferior frontal gyrus or dorsolateral prefrontal cortex where the voluntary decision to void can be made in light of social propriety. If voiding is not desired the medial prefrontal cortex is deactivated and this signal passes to the PAG and reinforces suppression of the voiding reflex. Backup continence mechanism: If the normal mechanism threatens to fail, as in OAB, the dACC is activated and generates a sensation of urgency together with output that tightens pelvic floor and sphincter muscles and relaxes the bladder, attempting thus to maintain continence. This signal may be relayed via the pontine continence center , (not shown). A third continence mechanism involves deactivation of parahippocampal complex, posterior cortex and perhaps hypothalamus. It may be concerned with basic safety.

Figure 2*

Images related to regional brain activity during scanning procedure (activations and deactivations during bladder filling and self-reported urgency). (A) Upper part (yellow): Group as a whole (n=30) - activations (P < 0.01 uncorrected); Lower part (blue): Group as a whole - deactivations (P < 0.05 uncorrected). (B) Upper part (red): DO group (n=9) - activations (P <0.01); Lower part (blue): No DO group (n=21) - deactivations (P < 0.05). (C) DO group: areas with significantly stronger activity during reported urgency compared to No DO group. (D) Upper part (yellow): DO group - areas with significantly stronger activity at lower bladder volumes compared to No DO group (P < 0.05 uncorrected); Lower part (blue): DO group - areas with significantly weaker activity at lower bladder volumes compared to No DO group (P < 0.05 uncorrected).* some results displayed at lower threshold level (P<0.05) for figure only (SMA=supplemental motor area; SFG=superior frontal gyrus; dACG=dorsal anterior cingulate gyrus; RI=right insula; dlPFC=dorsolateral prefrontal cortex; PFC=prefrontal cortex; IPL=inferior parietal lobule.)