Switching off micturition using deep brain stimulation at midbrain sites

Abstract

Most of the time the bladder is locked in storage mode, switching to voiding only when it is judged safe and/or socially appropriate to urinate. Here we show, in humans and rodents, that deep brain stimulation in the periaqueductal gray matter can rapidly and reversibly manipulate switching within the micturition control circuitry, to defer voiding and maintain urinary continence, even when the bladder is full. Manipulation of neural continence pathways by deep brain stimulation may offer new avenues for the treatment of urinary incontinence of central origin.

Effects of pedunculopontine nucleus stimulation on human bladder function

“…We found that the white matter pathways did not pass through the PAG, including subject 4, for whom DBS had a larger proportional effect on bladder capacity. The PAG has been hypothesized to act as a “micturition switch” and modulation of activity within the PAG by PPN DBS could be hypothesized to alter micturition control but this is not supported by our data.…”

“…It has been demonstrated that DBS of the subthalamic nucleus (STN) typically increases bladder capacity and reduces detrusor overactivity, while DBS of the thalamus significantly decreases bladder volume at “first” and “strong” desire to void and maximum bladder capacity . DBS of the globus pallidus interna in patients with dystonia reduces urine flow rate, increases post‐void residual, and reduces detrusor overactivity, and DBS of the periaqueductal gray area (PAG) increases maximal bladder capacity . This growing literature provides valuable information about potential targets for functional manipulation of bladder function and outlines urinary side‐effects from various targets.…”

Effect of electrical vs. chemical deep brain stimulation at midbrain sites on micturition in anaesthetized rats

“…In a preliminary study (Green et al . ), we showed that localized electrical stimulation at midbrain sites in rats and humans could promote continence. In this study, the effective sites in humans were quite widespread.…”

Deep brain stimulation and autonomic control

“…By matching as far as possible the experimental conditions, we showed in rats and humans that cystometric capacity (the bladder volume at which a void occurs in rats or the volume required to produce an intense desire to urinate in humans) increased during DBS (Fig. ; Green et al ). This effect could be evoked by stimulation over a much wider area of the midbrain than the caudal ventrolateral PAG, which contains the critical synapses in the micturition reflex pathway (Green et al ; E. Stone, J.H.…”