Control of bladder sensations: An fMRI study of brain activity and effective connectivity
Introduction
Control of urinary continence involves several levels of the central nervous system (Blok, 2002). Information on the intravesical pressure is encoded in the activity of thin myelinated afferent fibres (Häbler et al., 1993) and conveyed via the spinothalamic tract to the mesencephalic periaquaeductal grey (PAG), which in turn projects to the pontine micturition centre (PMC). In case of the voiding reflex, the PAG excites the PMC once the afferent input becomes strong enough (Griffiths, 2002). Efferent signals of the PMC then cause the bladder to contract and the urethral sphincter to relax until voiding takes place. The voiding reflex is normally controlled by cortical centres (Griffiths and Tadic, 2008). If necessary, healthy adults can therefore postpone micturition despite a full bladder and can deliberately initiate voiding even if the bladder is nearly empty. Previous neuroimaging studies have identified several cortical regions that are involved with the control of continence, namely the insula, the cingulate gyrus, and the prefrontal cortex (for reviews, see Griffiths and Tadic, 2008, Kavia et al., 2005).
Intact bladder control requires conscious perception of bladder filling (Griffiths, 2007). In general, the intensity of bladder sensation increases with bladder volume, progressing from a first sensation of filling, via a first desire to void, to a strong or even painful desire to void. However, the relationship between bladder volume and the intensity of the sensation is not fixed (Kavia et al., 2005). When the bladder is fairly full, the desire to void can be suppressed and ignored, but it can also be called forth deliberately. A previous fMRI study identified brain regions that were active during such intentional modulations of the desire to void in healthy female volunteers (Kuhtz-Buschbeck et al., 2005). During an urge (U) task, the women directed their attention to the sensations arising from the bladder and urethra and increased the desire to void as one does when initiating micturition. Since they did not allow urine to pass, this U-task represents “attempted micturition”. The task was performed ten times because fMRI requires averaging of frequently repeated events. The supplementary motor area (SMA), the cingulate cortex, the prefrontal and posterior parietal cortex, the insula and frontal operculum were more active during “attempted micturition” than during suppression of bladder sensations (Kuhtz-Buschbeck et al., 2005). Possible effects of the bladder volume on the task-related brain activity during “attempted micturition” were not previously analysed and corresponding data for men are lacking up to now.
The present fMRI study was therefore undertaken with the following goals: firstly, to identify brain regions that are consistently active during “attempted micturition”, using a conservative statistical threshold in a large group of normal volunteers (16 men, 17 women). Secondly, to test for gender-related differences in brain activity during this task. Thirdly, to study the effect of different bladder volumes by comparing measurements made at larger vs. smaller bladder volumes. Fourthly, to explore the effective connectivity of cortical regions involved in bladder control during “attempted micturition”. The importance of network interactions between brain regions in mediating sensorimotor and cognitive tasks is increasingly acknowledged (Horwitz et al., 2005). Up to now, however, only one very recent study has examined the connectivity of supraspinal bladder control regions by physiophysiological interaction analysis (Tadic et al., 2008).
Attention to visual stimuli is known to modulate the cortico-cortical connectivity of visual areas and posterior parietal regions (Friston et al., 2003). Could attention to bladder sensations have similar effects on the relevant brain regions? “Attempted micturition” requires interoceptive awareness and selective attention, which yield perceptual prominence to the desire to void. To investigate task-related changes of effective connectivity, we performed psychophysiological interaction (PPI) analyses (Friston et al., 1997). A PPI means that the contribution of one brain area (source region) to another area (target region) changes significantly with the psychological or cognitive context (here: attention to bladder sensations). Four source regions known to be involved in bladder control were chosen a priori, namely the cingulate cortex, the PAG, and the left and right insula. Among other functions, the cingulate cortex is implicated in interoceptive awareness and pain processing (Craig, 2002, Critchley et al., 2004), modulation of bodily arousal and autonomic responses (Critchley et al., 2003), and it is active during micturition (Blok et al., 1998, Nour et al., 2000). The PAG links afferent and efferent pathways of bladder control (Kavia et al., 2005). Afferent signals from the bladder and urethra are relayed via the PAG and thalamus to the insula, possibly with a predominance of the right side (Griffiths and Tadic, 2008). We expected the effective connectivity between these source regions and other brain areas (target regions) to change during “attempted micturition”, in comparison to a baseline (B) task, in which the desire to void was suppressed. Hence we looked for task-dependent influences from the source regions to other (“target”) brain regions.
Section snippets
Subjects and tasks
Thirty-three healthy adult volunteers (17 women, 16 men) gave their informed consent to participate in the study, which had been approved by the local ethics committee. Exclusion criteria comprised neurological or psychiatric disease, symptoms of urinary tract infection or incontinence, or any other problems that precluded being scanned. The age of the participants was 26.4 ± 4.2 years (mean ± SD). Most of them were medical students or staff members of the Urology Department at the University of
Results
All participants asserted that they were able to intentionally increase their desire to void during the U-task for about 30 s without losing urine (“attempted micturition”). In runs A and B (full bladder) a moderate or strong desire to void was perceived, while only a slight desire to void was felt in runs C and D, congruent with the lower bladder volume (Fig. 1). In all runs, the intensity of the bladder sensation decreased after voluntary contractions of the pelvic floor, and could be
Discussion
The intensity of bladder sensations generally increases with bladder volume, but the relation between these factors is complex (Athwal et al., 2001, Kavia et al., 2005). When the bladder is fairly full (∼ 300 ml), adults can suppress the urge to void for some time if necessary, e.g. when driving a car, but can also deliberately call forth this sensation, e.g. when voiding is to be initiated (Jänig, 1996). We analysed brain activity in 33 healthy volunteers who intentionally increased the desire
Conclusions
A set of frontoparietal brain regions, including the SMA, the midcingulate cortex, the bilateral insula, the frontal operculum, and the right prefrontal cortex, was consistently active when normal volunteers deliberately called forth the sensation of the desire to void (“attempted micturition”). The brain responses were stronger in women than in men. Activity in the right anterior insula and the PAG was enhanced at higher bladder volumes. The midcingulate cortex had stronger connectivity
Acknowledgments
Prof. Dr. M. Mehdorn and Prof. Dr. K.P. Jünemann provided scientific support and allowed access to the fMRI scanner. The help of A. Kalz and R. Neumann in preparation of the manuscript is gratefully acknowledged. This study was supported by the Deutsche Forschungsgemeinschaft (grant KU 1937/2-1).
References (54)
Central pathways controlling micturition and urinary continence
Urology
(2002)- et al.
Cognitive and emotional influences in anterior cingulate cortex
Trends Cogn. Sci.
(2000) - et al.
Changes in brain activity following sacral neuromodulation for urinary retention
J. Urol.
(2005) A systematic review of neuroimaging data during visceral stimulation
Am. J. Gastroenterol.
(2003)- et al.
Functional imaging of stress urinary incontinence
NeuroImage
(2006) - et al.
A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data
NeuroImage
(2005) - et al.
Psychophysiological and modulatory interactions in neuroimaging
NeuroImage
(1997) - et al.
How many subjects constitute a study?
NeuroImage
(1999) - et al.
Dynamic causal modelling
NeuroImage
(2003) - et al.
Brain control of normal and overactive bladder
J. Urol.
(2005)
Cerebral control of the bladder in normal and urge-incontinent women
NeuroImage
Cortical representation of the urge to void: a functional magnetic resonance imaging study
J. Urol.
Activation of the supplementary motor area (SMA) during voluntary pelvic floor muscle contractions—an fMRI study
NeuroImage
Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: a network analysis
NeuroImage
Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study
J. Urol.
Sex-related differences in IBS patients: central processing of visceral stimuli
Gastroenterology
Electrophysiological assessment of sensations arising from the bladder: are there objective criteria for subjective perceptions?
J. Urol.
Voluntary pelvic floor muscle control—an fMRI study
NeuroImage
Gender differences in voluntary micturition control — an fMRI study
NeuroImage
Abnormal connections in the supraspinal bladder control network in women with urge urinary incontinence
NeuroImage
Cytology and functionally correlated circuits of human posterior cingulate areas
NeuroImage
An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction
NeuroImage
Brain responses to changes in bladder volume and urge to void in healthy men
Brain
A PET study on cortical and subcortical control of pelvic floor musculature in women
J. Comp. Neurol.
A PET study on brain control of micturition in humans
Brain
Brain activation during micturition in women
Brain
Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators
BJU Int.
Cited by (53)
The periaqueductal gray and control of bladder function
2023, Neuro-Urology Research: A Comprehensive OverviewVoluntary versus reflex micturition control
2023, Neuro-Urology Research: A Comprehensive OverviewLinking bodily, environmental and mental states in the self—A three-level model based on a meta-analysis
2020, Neuroscience and Biobehavioral ReviewsCitation Excerpt :For urogenital functions, we primarily selected the micturition paradigm. In this paradigm, sensations from the bladder are studied via manipulating the bladder capacity by naturally (Kuhtz-Buschbeck et al., 2009) or manually (Mehnert et al., 2011) filling the bladder to induce different levels of desires to void. Please note that other than micturition, genital stimulation/sexual arousal are also important fields involved in interoceptive-processing.
Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study
2020, Physiology and BehaviorCitation Excerpt :Relevant to this is that exercised compared to nonexercised WAS animals demonstrated significant increases in rCBF within the decision-making loop of the micturition circuit, comprised of the cingulate and medial prefrontal cortex (prelimbic, infralimbic areas), as well the insula which may play a role in bladder sensation [63, 64], and more indirectly the limbic/paralimbic regions, including the amygdala (central, lateral, basolateral, basomedial, medial nuclei), hippocampus (dorsal, ventral), and hypothalamus (anterior, lateral-peduncular). These regions provide a ‘top-down’ decision point whether micturition should be inhibited or triggered [29, 30], and have been shown by others to be activated by passive bladder distension in the rat [65], as well as in human subjects [46, 66, 67]. Our findings suggest the possibility that chronic exercise training may decrease urinary frequency at two points of control in the micturition circuit.
Brainstem nuclei responsive to cystometry in both endometriosis and cystitis rat models: C-fos immunohistochemistry study
2024, Neurourology and UrodynamicsPhysiology of Micturition
2023, Textbook of Female Urology and Urogynecology: Clinical Perspectives