This study provides preliminary data on the relationship between urinary urgency and abnormal brain activity among women with OAB. In this work, activation of the ACG in OAB subjects correlated with sensations of increasing urinary urgency. Despite similar perceived levels of urinary urgency, Control subjects did not show similar ACG activation. This is in keeping with recent studies of interoceptive stress that have demonstrated ACG activation to be a determinant of behavioral and autonomic response to visceral stimuli, including that from bladder and bowel distension. When stressed by bladder distension ACG activation in patients with OAB may be related to recruitment of accessory pathways to prevent loss of bladder control.(19
During low volume bladder filling the urgency regressor in OAB subjects correlated with activation of both the right and left insula, while Control subjects showed a lesser extent of activation (right insula only). This parallels prior work that has shown more widespread activation of the insula among patients with poor bladder control.(11
)Activation of the insula is indicative of its role in processing afferent input from the autonomic nervous system in general and sensation from bladder distension specifically.
Other work has shown increased insular activation in response to greater degrees of bladder distension.(11
) However, we did not observe this phenomenon in our subjects. Several factors could be responsible for the observed lack of correlation between the urge regressor and insula activation at higher bladder volumes in our subjects. Both our control and OAB subject groups were homogenous in age and did not include the young adult women that would be expected to have the highest insular activation with bladder distension.(12
) Additionally, we chose to center bladder filling and emptying around the volume that patients felt a strong urge to void, rather than maximal bladder capacity (MCC) as used by Griffiths.(11
) This was based on concerns regarding subjects’ acceptance of bladder discomfort at the higher MCC volumes during fMRI scanning as well as the rationale that the strong urge volumes would more accurately reflect the subjects’ routine voiding volumes.
Alternatively, the lack of insular activation during high bladder volume runs performed towards the end of the fMRI task may represent habituation caused by repetitive stimuli to the bladder. Habituation to the repeated filling and emptying of the bladder during the fMRI task may have blunted the efferent output from the bladder, diminishing the brain’s response to bladder filling. Finally, given our small sample size we may have not had the necessary statistical power to detect this effect.
Regardless of the cause, our data raise the possibility that patient rated urgency scores may correlate better with ACG activation than with activation of the insula. This would suggest that perception of urinary urgency is more dependent on the autonomic and behavioral response to bladder distension (mediated through ACG) than upon direct sensory input (mediated via the insula).
The correspondence between ACG activation and perception of urinary urgency may have important therapeutic implications for the treatment of OAB, particularly for the use of behavioral therapy. Activation of the ACG and other portions of the limbic cortex are modulated by cortical areas involved with executive function including decision making in an emotional context or conflict resolution. Cortical areas, such as the prefrontal cortex, have the ability to inhibit limbic system activation and have been implicated in the therapeutic effects of distraction techniques, hypnosis treatment and the use of placebo. (20
The role of the ACG and its associated cortex, however, is extremely complex. Clinically applicable understanding will require not only knowledge of the magnitude of neural activation at these sites, but fMRI analysis of the neural connections between limbic cortex, prefrontal cortex, midbrain (PAG) and brainstem structures (PMC). This study’s demonstration of temporal correlation between ACG signal and subjects’ urgency (urge regressor) may add to the understanding of the relationship between brain activation and symptoms in OAB patients. Over the last decade the urologic and neuroscience literature have made significant advances in understanding the etiology and control of urinary incontinence by the use of functional brain imaging. We expect that our work is only the beginning of wider contribution by the obstetrics and gynecology community.