Cerebral control of the bladder in normal and urge-incontinent women

Abstract

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26-85 years): 11 "cases" with urge incontinence and DO (proven previously) and 10 normal "controls". Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In "controls", increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger "cases", ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly "cases" showed strong ACG responses even at small bladder volume but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase.

Conclusion: Among normal "controls", increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent "cases" and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older "cases" reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO).

Figures

Figure 1

Schematic diagram of bladder filling and scanning protocol. 4 blocks of measurements were made in all subjects. Blocks 5 and/or 6 were performed only if subjects agreed. Each block included 4 repetitions of a basic pattern of infusion and withdrawal. Reproduced from (Griffiths et al., 2005) by permission of the publisher, Elsevier.

Figure 2

Responses to bladder infusion in normal controls at large bladder volumes. Insular response is greater on the right. RI = right insula; ACG = anterior cingulate gyrus; H = hypothalamus; RI/PFC = right anterior insula and/or lateral prefrontal cortex. R = right side. Color bar shows scale of student's t values.

Figure 3

Responses to bladder infusion in subjects with urge incontinence at large bladder volumes. RI = right insula; ACG = anterior cingulate gyrus; PMC = pontine micturition center.

Figure 4

Correlation with age of response to bladder infusion at small bladder volumes. Left panel: in normal controls, areas of negative correlation with age (thresholded at P < 0.01). Right panel: in subjects with urge incontinence, areas of positive correlation with age (thresholded at P < 0.05 for display). Right posterior insula (white arrows) shows negative correlation with age in normal controls (in bilateral cluster, P < 0.0005,corrected) but positive correlation in urge-incontinent subjects (P < 0.01, uncorrected).