SMALL-WORLD BRAIN NETWORK IN WOMEN WITH OVERACTIVE BLADDER AND HEALTHY CONTROLS

Arya L1, Hui D2, Soriano A3, Rao H3

Research Type

Basic Science / Translational

Abstract Category

Neurourology

Abstract 276
Best Basic Science
Scientific Podium Session 16
Thursday 5th September 2019
10:30 - 10:45
Hall G3
Imaging Overactive Bladder Anatomy Pathophysiology Neuropathies: Central
1.University of Pennsyvania, 2.Unviersity of Pennsylvania, 3.University of Pennsylvania
Presenter
L

Lily Arya

Links

Abstract

Hypothesis / aims of study
Previous neuroimaging studies have shown that overactive bladder (OAB) is associated with functional abnormalities in specific brain regions; however, the extent to which brain network topology is altered by overactive bladder (OAB) remains unknown. Accumulating evidence from the recently emerging field of network neuroscience suggests that the human brain can be characterized as a small-world network which is optimally organized for efficient segregation and integration of information. The brain network topology in micturition states has not been measured.
The aim of this study is to use functional magnetic resonance imaging (fMRI) to explore brain small-world network changes during bladder filling in women with OAB and healthy controls.  We hypothesized that 1) changes in patient reported urinary urgency correlate with changes in small-world network metrics and 2) there are significant differences in small-world network metrics in the low and high urgency states between the brains of women with OAB and controls. To our knowledge, this is the first study to apply the concepts of small-world brain network topology to micturition.
Study design, materials and methods
Eleven women with OAB and 11 healthy controls underwent BOLD (blood oxygen level dependent) fMRI scanning in a Siemens 3T scanner in a low urgency state (empty bladder) after voiding and a high urgency state after drinking oral fluids. Urinary urgency ratings (using visual analogue scale 0-10) were obtained before and after each scan. All subjects completed the International Consultation on Incontinence Modular Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) questionnaire prior to undergoing imaging.  Using GRETNA toolbox, we conducted graph theoretical analysis of fMRI data to calculate brain small-world network metrics. In graph theory, the brain is described as a network, in which a node is an anatomically defined region and an edge is present when there is functional correlation between the two nodes. We measured the properties of the micturition network using the following indices: path length Lp (distance between pairs of nodes), clustering coefficient Cp (tendency to which neighboring nodes are connected), Lambda or λ (the ratio of the path length between the real and random network), Gamma or γ (the ratio of the clustering coefficients between the real and random network), Sigma or σ (the extent to which a network meets the properties of a small-world network, σ = γ/λ). We also calculated Global efficiency (Eglob), a measure of the global efficiency of parallel information transfer in the network.  Finally, we examined the relationships between network metrics and urgency scores.
Results
There was no significant difference in the age of women with OAB and controls (52.5 ± 16 versus 47 ± 15 years, p =0.42).  Women with OAB had significantly higher BMI (35.1 ± 12 versus 32 ±12, p = .04) and urgency bother score on ICIQ-FLUTS (8.5 ± 3 versus 0 ± 1, p < .001) than controls. In the low and the high urgency states, the brain networks of OAB patients and healthy controls demonstrated the features of small-world network by having a clustering coefficient higher than that of a random network (Gamma > 1), and a path-length similar to a random graph (Lambda ≈ 1).  In the low urgency state, path length as measured by Lambda was significantly shorter and global efficiency (Eglob) was significantly higher in women with OAB than controls (P<0.05) (Figure 1).   In the high urgency state, no significant difference in small-world metrics was noted between women with OAB and controls. Figure 2 shows the correlations between change in urinary urgency and change in small-world metrics. Greater change in urgency scores in the OAB group was negatively correlated with a change in the Lambda (r=-0.706, P=0.015) and positively correlated with a change in the Gamma (r=0.680, P=0.021) and a change in network small-worldness (Sigma, r=0.825, P=0.002). No such correlations were noted between urinary urgency scores and brain small-world properties in the control group.
Interpretation of results
Our study shows that regardless of the full or empty bladder state, the brain is organized as a small-world network in women with OAB and healthy controls. This is indicated by characteristic path length and small-world index greater than 1 in the low and high urgency states in women with OAB and controls.  These findings suggest that the small-world network is a useful framework that could be applied to understanding central mechanisms of OAB. 
We noted small but significant differences in small-world metrics between women with OAB and controls in the low urgency state.  Specifically, in the low urgency state before bladder filling, path length was shorter and global efficiency was greater in women with OAB than controls. Short characteristic path length reflects greater speed of information transfer in the brain network. Global efficiency is a measure of parallel information transfer in the network.  Our findings of shorter path length and greater global efficiency in the low urgency state in women with OAB may represent a compensatory mechanism where the OAB brain adjusts its network organization topology in the empty bladder state to adapt to or compensate for the high urgency experienced during bladder filling.
In the high urgency state, changes in urinary urgency were associated with change in small world metrics in women with OAB but not in controls.  These findings suggest that the brain micturition network adapts to bladder filling in healthy controls but not in women with OAB.
Concluding message
1. Small-world network metrics are a valid method to quantitatively measure the strength of functional connections between brain regions in micturition states. 
2. Urinary urgency may represent a failure of the brain network to adapt to bladder filling.  This new insight into mechanism underlying urgency opens the door to develop new centrally-based treatments for OAB.
3. The functional brain network of women with OAB is significantly different from that of controls at baseline and could potentially serve as a biomarker for the condition.
Figure 1 Relationship between small-world metrics in women with OAB and controls in the low urgency state
Figure 2 Relationship between urinary urgency and small-world metrics in women with OAB and controls
References
  1. Bassett DS, Bullmore ET. Small-World Brain Networks Revisited. Neuroscientist. 2016;23(5):499–516. The micturition switch and its forebrain influences.
  2. Rubinov M, Sporns O. 2011. Weight-conserving characterization of complex functional brain networks. Neuroimage 56(4):2068–79.
  3. Griffiths DJ, Fowler CJ. The micturition switch and its forebrain influences. Acta Physiol (Oxf). 2013 Jan;207(1):93-109. doi: 10.1111/apha.12019. Epub 2012 Nov 16.
Disclosures
Funding Center for Functional Neuroimaging, Perelman Scool of Medicine of the University of Pennsylvania Clinical Trial No Subjects Human Ethics Committee Institutional Review Board of the University of Pennsylvania Helsinki Yes Informed Consent Yes