Motor cortical neuromodulation of pelvic floor muscle tone: Potential implications for the treatment of urologic conditions

Abstract

Aims: In the human brain, supplementary motor area (SMA) is involved in the control of pelvic floor muscles (PFMs). SMA dysfunction has been implicated in several disorders involving PFMs, including urinary incontinence and urologic pain. Here, we aimed to provide a proof-of-concept study to demonstrate the feasibility of modulating resting PFM activity (tone) as well as SMA activity with noninvasive stimulation of SMA.

Methods: We studied six patients (3 women + 3 men) with Urologic Chronic Pelvic Pain Syndrome. Repetitive transcranial magnetic stimulation (rTMS) was applied to SMA immediately after voiding. We tested two rTMS protocols: high-frequency (HF-rTMS) which is generally excitatory, and low-frequency (LF-rTMS) which is generally inhibitory. PFM activity was measured during rTMS using electromyography. Brain activity was measured immediately before and after rTMS using functional magnetic resonance imaging.

Results: The rTMS protocols had significantly different effects on resting activity in PFMs (P = 0.03): HF-rTMS decreased and LF-rTMS increased pelvic floor tone. SMA activity showed a clear trend ( P = 0.06) toward the expected differential changes: HF-rTMS increased and LF-rTMS decreased SMA activity.

Conclusions: We interpret the differential effects of rTMS at the brain and muscle level as novel support for an important inhibitory influence of SMA activity on pelvic floor tone after voiding. This preliminary study provides a framework for designing future studies to determine if neuromodulation of SMA could augment therapy for chronic urologic conditions.

Keywords: cortical neuromodulation; pelvic floor muscle tone; pelvic pain; rTMS; supplementary motor area.

© 2019 Wiley Periodicals, Inc.

Figures

Figure 1.. Electromyographic (EMG) assessment of the effects of repetitive transcranial magnetic stimulation (rTMS).

A. Example of estimated time-series of changes in resting pelvic floor muscle (PFM) activity during high frequency (HF-rTMS) or low frequency rTMS (LF-rTMS). B. Four panels of raw demeaned PFM EMG signals, during an earlier (E) or later (L) stage of each rTMS protocol. Each panel shows 500 EMG signals, focusing on the 80-millisecond window after each rTMS pulse where the peak-to-peak difference of each signal was recorded and used to create a time-series of resting PFM activity, as shown in A. In each panel, the mean of the 500 signals is plotted in black, showing no evidence of consistent motor evoked potentials during rTMS. Comparing L to E shows an increase in EMG activity during LF-rTMS (top panels in B) and a decrease in EMG activity during HF-rTMS (bottom panels in B). Data in A and B are from the same participant (P2).

Figure 2.. Effects of repetitive transcranial magnetic stimulation (rTMS) on resting pelvic floor muscle (PFM) activity.

A. Group EMG data showing changes in resting PFM activity (mean and standard error), as measured from EMG immediately after each rTMS pulse, during either high frequency (HF-rTMS) or low frequency rTMS (LF-rTMS). P = participant. W = women. M = men. B. Individual EMG data showing changes in resting PFM activity during either HF-rTMS or LF-rTMS. P2 received LF-rTMS then HF-rTMS, opposite to the other 5 participants who received HF-rTMS then LF-rTMS. Data in B were used to create group results in A and C. C. The effects of HF-rTMS and LF-rTMS on the resting PFM activity outcome measure were significantly different.

Figure 3.. Effects of repetitive transcranial magnetic stimulation (rTMS) on resting brain activity around the representation of pelvic floor muscles (PFM) in supplementary motor area (SMA).

A. In each participant, high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS) targeted the same PFM representation in SMA, with one-week wash-out period. B. Group resting-state functional magnetic resonance imaging (rs-fMRI) data. Brain maps of rTMS-induced changes, as assessed using fALFF in the 0.01–0.027 Hz frequency band before and after either HF-rTMS or LF rTMS. C. The effects of HF-rTMS and LF-rTMS on the resting SMA activity outcome measure trended toward statistical significance.