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Background: Although there are several concepts regarding lower urinary tract (LUT) function and neuronal control in the normal and pathological condition, the exact pathophysiological mechanisms involved are largely unknown – especially in humans. To function correctly the lower urinary tract structures (bladder, bladder neck, urethra, and urethral sphincter) rely on intact neuronal innervation which is under the control of a complex supraspinal network. The dependence of the LUT on complex central neuronal circuits makes it vulnerable to neurological disorders. Thus, functional neuroimaging studies are a highly valuable tool to non-invasively investigate normal LUT function and dysfunction in neurogenic and non-neurogenic conditions in humans. In the last decade, several functional neuroimaging studies, including our own, have contributed to the understanding of the supraspinal neuronal control of the healthy human LUT and in conditions with LUT dysfunction. However, many questions still remain unanswered.

Objectives: First aim is to evaluate supraspinal LUT control in patients with non-neurogenic overactive bladders (NNOAB) and find out if there are specific differences in supraspinal activation, structural, and functional connectivity that might be characteristic for overactive bladder (OAB). The second aim is to evaluate the potential effect of intradetrusor injections of botulinum neurotoxin type A (BoNTA) on aberrant supraspinal LUT control in NNOAB. The third aim is to evaluate supraspinal LUT control in Multiple Sclerosis (MS) patients compared to healthy controls and NNOAB subjects to investigate the specific differences in supraspinal activation, and structural, and functional connectivity that might be characteristic for OAB in MS. The fourth aim is to investigate the potential involvement of abnormal C-fibre sensitivity in the pathophysiology of OAB symptoms in NNOAB and MS patients.

Importance and impact of the study: This project is the first to investigate supraspinal LUT control in healthy subjects and patients with neurogenic and non-neurogenic LUT dysfunction using fMRI in combination with diffusion tensor imaging (DTI) and functional connectivity (FC) analysis. In addition this project includes the first study investigating the effect of BoNTA on the supraspinal control which should provide profound insight into the supraspinal neuronal mechanisms and networks responsible for LUT control. The findings will help to verify, amend, and/or adjust neuronal circuitry models which were established from findings in healthy subjects in the context of neurogenic and non-neurogenic LUT dysfunction.