Resting state analysis of subthalamic nucleus functional connectivity across bladder states in Parkinson's disease

Roy H1, Roy C2, Griffiths D J3, Green A4, Menke R5

Research Type

Clinical

Abstract Category

Imaging

PRIZE AWARD: Best in Category Prize - Imaging
Abstract 36
Neurogenic Bladder
Scientific Podium Short Oral Session 4
Wednesday 29th August 2018
11:07 - 11:15
Hall A
Neuromodulation Imaging Neuropathies: Central
1. Nuffield Department of Surgical Sciences, Oxford University, 2. Oxford University Hospitals, 3. Pittsburgh University (retired), 4. Nuffield Department of Surgical Sciences, 5. Wellcome Centre for Neuroimaging, Oxford
Presenter
H

Ha Roy

Links

Abstract

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.
Results
Functional connectivity (FC) between the STN and the lingual gyrus was significantly lower in the full bladder compared with the empty bladder condition (signifying reduced connectivity in full bladder compared with empty bladder). This was the only significant change in STN connectivity corresponding with bladder state. Post hoc connectivity analysis using the lingual gyrus as a seed region demonstrated significant increases in FC between the lingual gyrus and multiple areas previously linked with bladder sensation (e.g. insula), and urinary urgency (e.g. anterior cingulate cortex) in the full compared with the empty bladder state.
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.
Concluding message
Brain imaging has revealed new aspects of the bladder control system: (1) a likely mechanism by which deep brain stimulation of the STN may improve bladder symptoms in PD; (2) the importance of the connectivity between STN and lingual gyrus; and (3) the extensive connections between the lingual gyrus and bladder sensory networks, which form a link not previously described between the deep brain (STN), the lingual gyrus and cortical regions involved in control of the bladder.
References
  1. Effects of high frequency deep brain stimulation on urine storage and voiding function in conscious minipigs. Dalmose AL, Bjarkam CR, Sorensen JC et al. Neururol Urodyn 2004;23(3):265-72
  2. Effect of subthalamic deep brain stimulation on the function of the urinary bladder. Seif C, Herzog J, van der Horst C, et al. Ann Neurol. 2004 Jan; 55(1):118-20
  3. Effects of subthalamic nucleus stimulation on urodynamics findings in patients with Parkinson's disease. Finazzi-Agro E, Peppe A, D'Amico A, et al . J Urol. 2003 Apr;169:1388-91
Disclosures
Funding Medical Research Council UK, Dunhill Medical Trust, Royal College of Surgeons England. Clinical Trial No Subjects Human Ethics Committee Oxfordshire REC B Helsinki Yes