JU INSIGHT Overactive Bladder Syndrome Subtypes: Symptoms of Lower Urinary Tract Dysfunction Research Network Results

By: Ishtiaq Mawla, PhD, University of Michigan, Ann Arbor; Andrew Schrepf, PhD, University of Michigan, Ann Arbor; Jason J. Kutch, PhD, University of Southern California, Los Angeles; Margaret E. Helmuth, MA, Arbor Research Collaborative for Health, Ann Arbor, Michigan; Abigail R. Smith, PhD, Arbor Research Collaborative for Health, Ann Arbor, Michigan; Eric Ichesco, BS, University of Michigan, Ann Arbor; Claire C. Yang, MD, University of Washington, Seattle; Victor P. Andreev, PhD, Arbor Research Collaborative for Health, Ann Arbor, Michigan; Karl J. Kreder, MD, University of Iowa Carver College of Medicine, Iowa City; Catherine S. Bradley, MD, University of Iowa Hospitals and Clinics, Iowa City; Vincent A. Magnotta, PhD, University of Iowa, Iowa City; Ziya Kirkali, MD, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; Richard E. Harris, PhD, University of Michigan, Ann Arbor School of Medicine, University of California at Irvine; H. Henry Lai, MD, Washington University in St Louis, Missouri; Steven E. Harte, PhD, University of Michigan, Ann Arbor and the LURN Study Group | Posted on: 19 Jan 2024

Mawla I, Schrepf A, Kutch JJ, et al. Naturalistic bladder filling reveals subtypes in overactive bladder syndrome that differentially engages urinary urgency-related brain circuits: results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). J Urol. 2024;211(1):111-123.

Study Need and Importance

Bladder function is regulated not only by peripheral organs, but also via supraspinal circuits in the brain. The goal of this multisite resting state functional MRI (fMRI) study from LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) was to understand aberrant brain circuitry underlying overactive bladder (OAB) using an ecologically relevant naturalistic bladder-filling paradigm. Brain fMRI scans from OAB patients and controls were compared with an empty bladder and a full bladder.

What We Found

Two distinct bladder-filling phenotypes were identified among treatment-seeking OAB patients: OAB-2 patients responded to naturalistic bladder filling and reported increasing urinary urgency ratings as their bladder filled, whereas OAB-1 patients and most controls (CON-1) reported persistently low urgency ratings (<2 out of 10) or no increased urinary urgency with bladder filling. OAB-2 patients were more likely to have urgency urinary incontinence, more severe OAB symptoms, and worse quality of life than OAB-1 patients. Brain fMRI revealed differences in neural functioning between these 2 OAB subtypes, namely, sensorimotor-prefrontal connectivity is a key locus in OAB-2 patients with higher urinary urgency (Figure).

Figure. Association of change (Δ) in brain network connectivity (conn) with Δ in urgency due to natural bladder filling in patients who responded to naturalistic bladder filling and reported increasing urinary urgency ratings as their bladder filled (OAB-2). A, Increased default mode network (DMN) conn to the left (L) dorsolateral prefrontal cortex (dlPFC) encoded increased urgency. B, Increased sensorimotor network (SMN) conn to the dorsomedial prefrontal cortex (dmPFC) encoded increased urgency. C, Increased salience network (SLN) conn to L middle frontal gyrus (MFG), L primary motor cortex (M1), precuneus, and right (R) supramarginal gyrus (SMG) encoded increased urgency. D, Increased dorsal attention network (DAN) conn to the L and R primary somatosensory (S1)/M1, L anterior insula (aINS), L parahippocampal gyrus (PHG), and L hippocampus (Hipp) encoded increased urgency.

Limitations

Limitations of the study are (1) lack of urodynamics data on detrusor overactivity, (2) lack of bladder diary data, (3) low urgency ratings in the OAB-1 group may be related to a lower bladder volume or sensation of fullness, and (4) reports of urgency were made in the supine position while inside the MRI scanner.

Interpretations for Patient Care

Our study revealed 2 OAB phenotypes in response to naturalistic bladder filling with differences in neuropathophysiology. Brain fMRI data suggested that communication between sensorimotor and cognitive control/self-referential systems underlies the heightened stimulus-perception relationship observed in OAB patients with higher urinary urgency in response to bladder filling. These brain regions may be targeted for intervention.