Neuroimaging of Situational Triggers for Urgency Incontinence

Clarkson B1, Wei A1, Karim H1, Resnick N1, Perera S1, Tyagi S1, Conklin C1

Research Type

Clinical

Abstract Category

Female Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 682
Urology - Best of the Rest
Scientific Podium Short Oral Session 32
Friday 6th September 2019
15:45 - 15:52
Hall H2
Urgency Urinary Incontinence Female Incontinence Pathophysiology Sensory Dysfunction
1.University of Pittsburgh
Presenter
B

Becky Clarkson

Links

Abstract

Hypothesis / aims of study
The aim of this study was to investigate brain activity associated with situational triggers of urgency urinary incontinence (UUI), e.g. latch-key incontinence or similar triggers. This work builds on previous studies showing that reactions to situational triggers can be reproduced by displaying personalized images during urodynamic testing[1]. Specifically, our aim was to identify differences in brain reactivity during exposure to images depicting urgency trigger situations compared with safe situations.  Here we present our preliminary analysis.
Study design, materials and methods
Women over 40 years of age reporting situational UUI in at least two venues with more than one leak per week were recruited.  Situational UUI was assessed during interview and defined as a location or situation which would induce urgency more than half the time (e.g. approaching front door; washing dishes). ‘Safe situations’ were defines as those which would never or rarely induce feelings of urgency or leakage. Since no questionnaires are validated for situational urgency, semi-structured interviews adapted from those used in smoking studies were administered along with in-depth qualitative interview, coupled with results from bladder diary. Participants used a standard camera to take photos of 4 ‘cue situations’ and 4 ‘safe situations’ to simulate approach to (e.g. the front door), or the action of (e.g. running water/kitchen sink), a stimulus. Written and verbal instructions were given to ensure consistency and quality of photos. A standardized slideshow was constructed with these photos for display in the MRI scanner. The participant had two 7 Fr single lumen urethral catheters placed for filling and measuring bladder pressure (pves; Laborie Goby). Structural and functional brain images were taken with a 3T MRI scanner (Siemens Biograph mMR). fMRI BOLD (Blood oxygen level dependent) scans were taken during image display with two bladder states: ‘empty’ (10-30 mins post drainage) and ‘full’ (until the participant signaled a desire to urinate which could be postponed for 10-15 minutes, specifically ‘until the next commercial break of your favorite TV show’). The image sequence consisted of a baseline bladder fullness question (see results for specifics) followed by a four second showing of four photos of a particular scenario, followed by a further question about the effect of the images on the bladder. Questions were answered using push buttons on a glove. Each of the 4 cue and safe scenarios were presented using this ‘question-image-question’ sequence, in a random order. Bladder pressure was monitored and instances of detrusor overactivity noted.  MRI data was analyzed using SPM12 (Wellcome trust, UK). First-level statistical analysis comprised calculation of Student’s t for paired signal contrasts, reducing the images to a single 3D map of t-values. BOLD images during were summed over the four 16 second trigger image display and separately over the four 16 second safe image display to create the trigger vs safe contrasts using a two-sample t-test thresholded at p<0.01 (uncorrected) with a minimum cluster size of 20 voxels.
Results
A total of 18 women of mean (SD) age 61.8(8.9) years had mean (SD)  1.9 (1.2) leaks per 24 hour period on 3-day bladder diary. All participants identified at least three trigger or safe situations. 
Self-report volume sensation is indexed as the answer to the pre-image question ‘how full does your bladder feel?’ on a scale of 1 – ‘empty’ to 5 – ‘full and I need to go right now’. Mean (SD) volume sensation at ‘Empty’ was 2.3 (0.8) and at ‘Full’, 3.7(0.8). 
In answer to the post-image question: How does seeing these pictures make your bladder feel? Answer: -2 - much worse, -1 - a little worse, 0 - no change, +1 - a little better, +2 - much better), mean(SD) reaction to ‘safe conditions’ was -0.2(0.7) on an empty bladder and +0.2(0.8) on a full bladder,  and to ‘trigger’ scenarios was +0.4 (0.7) on an empty bladder and +1.2 (0.6) on a full bladder. Using a mixed model comparison analyzing the post-photo rating while adjusting for baseline fullness, we found  responses to the safe scenarios to be significantly different to the trigger scenarios at p<0.001, with greater effect at larger volumes.
Analysis of brain activity using a threshold of p<0.01 (uncorrected), showed more activation during the trigger rather than the safe images in the middle frontal gyrus, the medial frontal gyrus, the cingulate gyrus, culmen, and parahippocampal gyrus areas (see fig 1). Only the precuneus showed more activity during the trigger images on an empty bladder.  On both a full and empty bladder, we saw increased activity in the precentral gyrus in safe areas compared to trigger areas.
Interpretation of results
The self-report questions in the MRI scanner confirmed both the differing sensations in the full vs empty bladder and that trigger situations had a significantly more negative effect on the perception of bladder sensation than the safe scenarios. This suggests that even within the unusual setting of the MRI scanner with a relatively small visual stimulus, participants report that the images have some effect.
Comparison of brain activity on the empty bladder scan showed more activity in the precuneus during trigger photos compared to safe photos. This area is associated with visuospatial processing and episodic memory, suggestive that these images are evoking recall of the trigger scenarios in a stronger way than in the safe scenarios. In both the full and empty bladder scans, only the precentral gyrus, a motor-related area, is more active during safe than trigger scenarios, the significance of which is unclear. During full bladder scans there are a number of brain areas that are significantly more active during trigger image display. Areas such as the middle and medial frontal gyri are main components of the attention network and decision-related processes, with the middle frontal gyrus being specifically involved in re-orienting to unexpected stimuli [2] suggestive that there is significant attentional processing occurring specifically when exposed to triggering images. In addition, areas well known to be involved in the continence mechanism, such as the cingulate and parahippocampal areas are also active. This is especially interesting since bladder volume is constant, therefore the activation in bladder related areas appears to be provoked solely by the visual stimulus.
Concluding message
We were able to evoke a self-reported increase in bladder sensation solely by showing images of personalized urgency trigger situations within an MRI scanner, regardless of fullness of bladder. We were also able to demonstrate a significant difference in brain reactivity to trigger vs safe stimuli. The active areas suggest that environmental cues can stimulate activity in bladder-related brain circuits and additionally in executive processing networks. This work represents, for the first time, a measurable central reaction related to the long understood phenomenon of latch-key incontinence. It will help us understand continence control mechanisms, and will allow us to better understand processing of external stimuli in relation to continence. This will allow us to further differentiate between bladder- and brain-based dysfunction to better target treatments. Treatments targeting this particular dysfunction include behavioral therapies to extinguish environmental cues.
Figure 1 Brain areas with greater activity during trigger vs safe scenarios
References
  1. Journal of Urology. 2015;193(4):e489-90
  2. Front Syst Neurosci. 2015;9:23
Disclosures
<span class="text-strong">Funding</span> NIH R21 AG053788 <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> University of Pittsburgh Institutional Review Board <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes