Brain Areas Involved in Bladder Filling and Contraction

Overactive Bladder Syndrome The International Continence Society (ICS) has defined Overactive Bladder syndrome (OAB) as a medical condition with symptoms of urgency, with or without incontinence, usually with frequency and nocturia, with no proven infection of obvious pathology.

OAB has an overall prevalence in Western Europe and the United States of 16% to 17%. Epidemiological evidence indicates that symptoms of OAB are common and likely to affect up to 50-100 million persons worldwide. In the EPIC study which was conducted in 5 countries in > 19000 men and women aged > 18 years, using the ICS definitions for OAB, the prevalence of OAB was 10.8% in men and 12.8% in women, and its prevalence increased with age. The prevalence in women for storage was 59.2%, in voiding 19.5% and in post micturition symptoms 14.2%.

The fundamental symptom is urgency, which is widely considered to be the driver of other urological symptoms. Urgency is a sudden compelling desire to pass urine, which is difficult to defer. The urological symptoms can have a considerable negative impact on quality of life, typically resulting in embarrassment and loss of dignity, which might affect relationships, intimacy and self-image.

Conventional urodynamic test Diagnostic testing of lower urinary tract function by performing urodynamic investigations is currently widely accepted. The aim of the clinical urodynamics is to produce symptoms whilst making precise measurements in order to identify underlying causes for the symptoms and to quantify the related pathophysiological processes. Urodynamics allows direct assessment of lower urinary tract function by the measurement of physiological parameters (e.g. voiding pressure parameters; minimal urethral opening detrusor pressure and urethral resistance factor), micturitions volume and leakage volume).

Urodynamics cannot be performed as an automated protocol due to current limitations of urodynamic equipment and the lack of consensus on the precise method of measurement, signal processing, quantification, documentation and interpretation. The Good Urodynamic Practices developed by ICS provides guidelines regarding the strategy for urodynamic measurement, equipment set up and configuration, signal testing, plausibility controls, pattern recognition, and artefact correction.

During cystometry, involuntary detrusor contractions can only be found in 40% to 60% of patients with OAB symptoms. Detrusor overactivity contractions can occur either during filling or at the end. Conventional urodynamic remains the gold standard for investigating lower urinary tract dysfunction.

Functional Magnetic Resonance Imaging fMRI is an imaging modality that has recently been further developed to study the different parts of the human body through blood flow changes. In close collaboration with Maastricht University, Scannexus has made multiple 7 Tesla MRI scans available for our study in order to gain further insight into brain functioning areas.

Bladder Sensations Most of the understanding on the experience of bladder sensation during filling in normal individuals is based upon the work of Wyndaele and De Wachter. The sensation scoring system developed seek to determine the underlying reasons an individual patient usually void and is not meant to serve as an index of urgency or severity. The 4-point scoring scale ranges from voiding out of convenience (no urgency=0) to desperate urgency score=3) to capture perception of urgency on a continuum rather per se. The condition is recognised clinically as the 'Overactive Bladder (OAB) Symptom Complex'. It is associated with increased sensations to void which result in an increased voiding frequency, as determined from voiding diaries. OAB is further characterised during cystometric investigation by the occurrence of involuntary contractions of the bladder during the filling phase and, typically in the 'full bladder' by a strong sensation described as 'urgency' (a strong compelling desire to void that cannot be deferred which is more intense than a normal urge to void).

Overactive bladder syndrome (OAB) is associated with episodic increased bladder sensations to void, which result in increased in voiding frequency. During cystometric investigations, OAB is also characterised by the occurrence of involuntary bladder contractions during the filling phase and typically in the full bladder, a strong sensation described as urgency (described as a strong compelling desire to void that cannot be deferred and is more intense than the normal urge to void). It is during these urgency episodes that leakages (urgency incontinence) sometimes occur. In 46% of patients with the sensation of urgency, it is associated with bladder contractions.

Many studies investigated the link between patient reported sensations and bladder properties using standard rapid fill cystometry. This leads to the concept that bladder sensation is episodic. These episodic sensations are supposedly greater in patients with OAB and occur in lower bladder volumes, thus generating the sensation of urgency and more frequent voiding.

As described in literature sensations associated with bladder filling were different from those of imminent voiding. The sensations during filling were associated with a generalised feeling in the lower abdomen while the more intense sensations of imminent pre-void were located deeper down in the urethra. This anatomical variation may reflect different sensations and different underlying mechanisms. This supports that there are two systems generating sensation: 'continuous sensation' associated with the early filling phase and intense phasic sensations associated with the urethra.

An alternative view of bladder sensation was formulated many years ago. It proposes that the information from the bladder is generated continuously and that an awareness of bladder volumes is available through the entire filling phase. This is supported by neuro-physiological data demonstrating an almost continuous afferent outflow from the bladder receptors as the bladder fills. As a conclusion the physiological bases of the sensation or "urge" or "urgency" is still unknown.

Moreover, patients with OAB with or without detrusor overactivity (DO) on urodynamics all have in common that they have a sense of urgency. This sense is described as a sudden, compelling desire to void, which cannot be postponed. Affected individuals have the fear to loose urine (incontinence) and some even actually do. It is still not known if the same brain areas are involved in a normal desire to void in controls, as in OAB patients both with and without DO when they feel urgency. In our study we would like to answer this question by conducting simple urodynamics during an fMRI scan while the patient's bladder is filled through normal diuresis and their sense of urgency is registered through a push button.

In the past a few studies have been conducted with the fMRI of the central nervouse system in relation to bladder control. Poor bladder control has been reported to be specifically associated with inadequate activation of orbitofrontal cortex. Clinically, frontal cortical lesions are known to cause bladder control problems.. In addition, urinary urgency in patients with OAB was shown to be associated with increased activation of the limbic cortex through fMRI studies in women with OAB. A more recent study with fMRI showed that there were significant and vast changes in the brain's functional connectivity when bladder is filled, suggesting that the central process responsible for the increased control during the full bladder state appears to largely rely on the how distributed brain systems. In all these studies, a 3 Tesla fMRI has been used. The 7 Tesla fMRI which is intended to be used in our study will enable us to study brain areas that are more difficult to assess with 1,5 and 3 Tesla.

Moreover, none of the previous studies have included a protocol to measure bladder pressure, bladder sensation and fMRI scans of the brain simultaneously.