Hypothesis / aims of study
Subthalamic nucleus (STN) deep brain stimulation (DBS), an established treatment for Parkinson’s disease (PD), has been shown to modify urine storage characteristics in animals models (1) and improve overactive bladder symptoms and urodynamic storage function in PD patients with DBS electrodes implanted for treatment of movement disorder symptoms (2,3). Understanding of the mechanisms underlying these changes should lead to improved treatment of overactive bladder problems in PD, and possibly in other conditions also. As a first step we aimed to investigate the connections of the STN in PD patients, and in particular how they changed with bladder filling, using magnetic resonance (MR) resting-state functional connectivity analysis.
Study design, materials and methods
11 DBS-naive PD subjects underwent resting state fMRI scans in two bladder states: (1) “full bladder” and (2) “empty bladder”. Subjects were required to withhold their morning Parkinson’s medications on the day of testing. 2 subjects were excluded from further analysis, 1 due to caffeine consumption and 1 due to dopaminergic medication on the morning of scanning.
The full bladder scan was carried out first, during which two 7.5 minute BOLD sequences were run. Subjects were asked to rate their sensation of bladder fullness according to the following scale (0 = no bladder sensation, 1 = first sensation of bladder filling, 2= first desire to void, 3 = normal desire to void, 4 = strong desire to void, 5 = maximal bladder capacity) before each scan started. Following the 2 scans, subjects voided to empty their bladder and returned to the scanner. Two further 7.5 minute BOLD sequences were run, and a high-resolution structural scan was also obtained. Data was preprocessed and denoised in the standard way with motion correction, brain extraction, B0 unwarping, high pass filtering and smoothing using a Gaussian kernel of 8mm full width half maximum (FWHM). ICA denoising was then carried out, to remove signal related to movement, vasculature, CSF and other artefactual sources. This was done with reference to standard network templates and normal frequency ranges for brain network activity. Right and left STN masks were created using the subthalamic nucleus atlas available in the FMRIB software library (FSL). Dual regression was run using a paired t test design (comparing full and empty bladder conditions) with the STN mask as a seed.
Interpretation of results
These data suggest that an STN-lingual gyrus pathway plays a critical part in bladder control in PD, and in particular in the improvement in bladder symptoms following STN DBS. Potentially, DBS may augment STN FC with the lingual gyrus as the bladder fills, and thus, via the numerous cortical connections of this brain region, gain access to bladder sensory networks such as those centred on the insula and anterior cingulate, so enabling improved bladder control.