Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neural control of micturition in humans: a working model

Nature Reviews Urology volume 12, pages 695–705 (2015)Cite this article

Subjects

Key Points

  • Neural control of the bladder is complex, but many aspects can be accounted for by a simple working model

  • In this model, a few forebrain circuits, acting on the midbrain, can advance or delay the triggering of the voiding reflex and generate bladder sensations, such as desire to void

  • Understanding these circuits might, in the future, offer a new route to more effective treatments of urgency incontinence or overactive bladder

  • This new knowledge might shift clinical attention toward behavioural and/or electrophysiological treatments, or even direct stimulation of the deep brain

Abstract

Results from functional brain scanning have shown that neural control of the bladder involves many different regions. Yet, many aspects of this complex system can be simplified to a working model in which a few forebrain circuits, acting mainly on the midbrain periaqueductal grey (PAG), advance or delay the triggering of the voiding reflex and generate bladder sensations according to the volume of urine in the bladder, the safety of voiding and the emotional and social propriety of doing so. Understanding these circuits seems to offer a route to treatment of conditions, such as urgency incontinence or overactive bladder, in patients without overt neurological disease. Two of these circuits include, respectively, the medial prefrontal cortex and the parahippocampal complex, as well as the PAG. These circuits belong to a well-known network that is active at rest and deactivated when attention is required. Another circuit, comprising the insula and the midcingulate or dorsal anterior cingulate cortex, is activated by bladder filling and belongs to a salience network that generates sensations such as the desire to void. Behavioural treatments of urgency incontinence lead to changes in brain function that support the working model and suggest the mechanism of this type of treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Simple working model of LUT control.
Figure 2: Brain activity during pelvic floor muscle contractions.
Figure 3: Brain responses to bladder filling.
Figure 4: Responses to bladder filling in women with UUI.

Similar content being viewed by others

References

  1. de Groat, W. C., Griffiths, D. & Yoshimura, N. Neural control of the lower urinary tract. Compr. Physiol. 5, 327–396 (2015).

    PubMed  PubMed Central  Google Scholar 

  2. Fowler, C. J., Griffiths, D. & de Groat, W. C. The neural control of micturition. Nat. Rev. Neurosci. 9, 453–466 (2008).

    Article  CAS  Google Scholar 

  3. Griffiths, D., Tadic, S. D., Schaefer, W. & Resnick, N. M. Cerebral control of the bladder in normal and urge-incontinent women. Neuroimage 37, 1–7 (2007).

    Article  Google Scholar 

  4. Griffiths, D. J. & Fowler, C. J. The micturition switch and its forebrain influences. Acta Physiol. (Oxf.) 207, 93–109 (2013).

    Article  CAS  Google Scholar 

  5. Kavia, R. B., Dasgupta, R. & Fowler, C. J. Functional imaging and the central control of the bladder. J. Comp. Neurol. 493, 27–32 (2005).

    Article  Google Scholar 

  6. Blok, B. F. & Holstege, G. The central nervous system control of micturition in cats and humans. Behav. Brain Res. 92, 119–125 (1998).

    Article  CAS  Google Scholar 

  7. Abrams, P., Cardozo, L., Khoury, S. & Wein, A. (eds). Incontinence: fourth international consultation on incontinence (Health Publication, 2009).

    Google Scholar 

  8. Hartmann, K. E. et al. Treatment of overactive bladder in women. Evid. Rep. Technol. Assess. (Full Rep.) 2009, 1–120 (2009).

    Google Scholar 

  9. Stewart, W. F. et al. Prevalence and burden of overactive bladder in the United States. World J. Urol. 20, 327–336 (2003).

    CAS  PubMed  Google Scholar 

  10. Abrams, P. et al. The standardisation of terminology of lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Neurourol. Urodyn. 21, 167–178 (2002).

    Article  Google Scholar 

  11. Shy, M. et al. Functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating micturition. J. Urol. 192, 1149–1154 (2014).

    Article  Google Scholar 

  12. Beckel, J. M. & Holstege, G. Neuroanatomy of the lower urinary tract. Handb. Exp. Pharmacol. 202, 99–116 (2011).

    Article  CAS  Google Scholar 

  13. Linnman, C., Moulton, E. A., Barmettler, G., Becerra, L. & Borsook, D. Neuroimaging of the periaqueductal gray: state of the field. Neuroimage 60, 505–522 (2012).

    Article  Google Scholar 

  14. Holstege, G. Micturition and the soul. J. Comp. Neurol. 493, 15–20 (2005).

    Article  Google Scholar 

  15. Holstege, G. The emotional motor system and micturition control. Neurourol. Urodyn. 29, 42–48 (2010).

    Article  Google Scholar 

  16. Griffiths, D. & Apostolidis, A. in pelvic organ dysfunction in neurological disease: clinical management and rehabilitation (eds Fowler, C. J., Panicker, J. & Emmanuel, A.) 1–24 (Cambridge University Press, 2010).

    Book  Google Scholar 

  17. Morrison, J. F. The discovery of the pontine micturition centre by F. J. F. Barrington. Exp. Physiol. 93, 742–745 (2008).

    Article  Google Scholar 

  18. Barrington, F. J. The effect of lesions of the hind- and mid-brain on micturition in the cat. Q. J. Exp. Physiol. 15, 81–102 (1925).

    Article  Google Scholar 

  19. Barrett, L. F. & Satpute, A. B. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain. Curr. Opin. Neurobiol. 23, 361–372 (2013).

    Article  CAS  Google Scholar 

  20. Raichle, M. E. & Snyder, A. Z. A default mode of brain function: a brief history of an evolving idea. Neuroimage 37, 1083–1090 (2007).

    Article  Google Scholar 

  21. Matsumoto, S., Ishikawa, A., Kume, H., Takeuchi, T. & Homma, Y. Near infrared spectroscopy study of the central nervous activity during artificial changes in bladder sensation in men. Int. J. Urol. 16, 760–764 (2009).

    Article  Google Scholar 

  22. Matsumoto, S., Ishikawa, A., Matsumoto, S. & Homma, Y. Brain response provoked by different bladder volumes: a near infrared spectroscopy study. Neurourol. Urodyn. 30, 529–535 (2011).

    Article  Google Scholar 

  23. Sakakibara, R. et al. Tolterodine activates the prefrontal cortex during bladder filling in OAB patients: A real-time NIRS-urodynamics study. Neurourol. Urodyn. 33, 1110–1115 (2014).

    Article  CAS  Google Scholar 

  24. Blok, B. F., Willemsen, A. T. & Holstege, G. A PET study on brain control of micturition in humans. Brain 120, 111–121 (1997).

    Article  Google Scholar 

  25. Athwal, B. S. et al. Brain responses to changes in bladder volume and urge to void in healthy men. Brain 124, 369–377 (2001).

    Article  CAS  Google Scholar 

  26. Nour, S., Svarer, C., Kristensen, J. K., Paulson, O. B. & Law, I. Cerebral activation during micturition in normal men. Brain 123, 781–789 (2000).

    Article  Google Scholar 

  27. Zhang, H. et al. An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction. Neuroimage 24, 174–180 (2005).

    Article  Google Scholar 

  28. Griffiths, D., Derbyshire, S., Stenger, A. & Resnick, N. Brain control of normal and overactive bladder. J. Urol. 174, 1862–1867 (2005).

    Article  Google Scholar 

  29. Tadic, S. D., Griffiths, D., Schaefer, W. & Resnick, N. M. Abnormal connections in the supraspinal bladder control network in women with urge urinary incontinence. Neuroimage 39, 1647–1653 (2008).

    Article  Google Scholar 

  30. Nardos, R. et al. Examining mechanisms of brain control of bladder function with resting state functional connectivity MRI. Neurourol. Urodyn. 33, 493–501 (2014).

    Article  Google Scholar 

  31. Griffiths, D. J., Tadic, S. D., Schaefer, W. & Resnick, N. M. Cerebral control of the lower urinary tract: how age-related changes might predispose to urge incontinence. Neuroimage 47, 981–986 (2009).

    Article  Google Scholar 

  32. Kuhtz-Buschbeck, J. P. et al. Control of bladder sensations: an fMRI study of brain activity and effective connectivity. Neuroimage 47, 18–27 (2009).

    Article  CAS  Google Scholar 

  33. Abrams, P. et al. Fourth international consultation on incontinence recommendations of the international scientific committee: evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence. Neurourol. Urodyn. 29, 213–240 (2010).

    Article  CAS  Google Scholar 

  34. Kuhtz-Buschbeck, J. P. et al. Activation of the supplementary motor area (SMA) during voluntary pelvic floor muscle contractions—an fMRI study. Neuroimage 35, 449–457 (2007).

    Article  CAS  Google Scholar 

  35. Seseke, S. et al. Voluntary pelvic floor muscle control—an fMRI study. Neuroimage 31, 1399–1407 (2006).

    Article  CAS  Google Scholar 

  36. Blok, B. F., Sturms, L. M. & Holstege, G. A PET study on cortical and subcortical control of pelvic floor musculature in women. J. Comp. Neurol. 389, 535–544 (1997).

    Article  CAS  Google Scholar 

  37. Schrum, A., Wolff, S., van der Horst, C. & Kuhtz-Buschbeck, J. P. Motor cortical representation of the pelvic floor muscles. J. Urol. 186, 185–190 (2011).

    Article  CAS  Google Scholar 

  38. Tadic, S. D., Tannenbaum, C., Resnick, N. M. & Griffiths, D. Brain responses to bladder filling in older women without urgency incontinence. Neurourol. Urodyn. 32, 435–440 (2013).

    Article  Google Scholar 

  39. Matsuura, S. et al. Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. J. Urol. 168, 2035–2039 (2002).

    Article  Google Scholar 

  40. Kong, J., Tu, P. C., Zyloney, C. & Su, T. P. Intrinsic functional connectivity of the periaqueductal gray, a resting fMRI study. Behav. Brain Res. 211, 215–219 (2010).

    Article  Google Scholar 

  41. Mehnert, U. et al. Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve—an fMRI study in healthy women. Neuroimage 41, 682–689 (2008).

    Article  Google Scholar 

  42. Holstege, G., Griffiths, D., de Wall, H. & Dalm, E. Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat. J. Comp. Neurol. 250, 449–461 (1986).

    Article  CAS  Google Scholar 

  43. Seseke, S. et al. Gender differences in voluntary micturition control: an fMRI study. Neuroimage 43, 183–191 (2008).

    Article  CAS  Google Scholar 

  44. Mayer, E. A., Naliboff, B. D. & Craig, A. D. Neuroimaging of the brain-gut axis: from basic understanding to treatment of functional GI disorders. Gastroenterology 131, 1925–1942 (2006).

    Article  Google Scholar 

  45. Craig, A. D. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666 (2002).

    Article  CAS  Google Scholar 

  46. Blok, B. F., Sturms, L. M. & Holstege, G. Brain activation during micturition in women. Brain 121, 2033–2042 (1998).

    Article  Google Scholar 

  47. Komesu, Y. M., Ketai, L. H., Mayer, A. R., Teshiba, T. M. & Rogers, R. G. Functional MRI of the brain in women with overactive bladder: brain activation during urinary urgency. Female Pelvic Med. Reconstr. Surg. 17, 50–54 (2011).

    Article  Google Scholar 

  48. Tadic, S. D. et al. Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol. Urodyn. 31, 652–658 (2012).

    Article  Google Scholar 

  49. Griffiths, D., Clarkson, B., Tadic, S. D. & Resnick, N. M. Brain mechanisms underlying urge incontinence and its response to pelvic floor muscle training. J. Urol. 194, 708–715 (2015).

    Article  Google Scholar 

  50. Wager, T. D. et al. Brain mediators of cardiovascular responses to social threat, part II: Prefrontal-subcortical pathways and relationship with anxiety. Neuroimage 47, 836–851 (2009).

    Article  Google Scholar 

  51. Herzog, J. et al. Improved sensory gating of urinary bladder afferents in Parkinson's disease following subthalamic stimulation. Brain 131, 132–145 (2008).

    Article  Google Scholar 

  52. Green, A. L. et al. Switching off micturition using deep brain stimulation at midbrain sites. Ann. Neurol. 72, 144–147 (2012).

    Article  Google Scholar 

  53. Wager, T. D. et al. Brain mediators of cardiovascular responses to social threat: part I: Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity. Neuroimage 47, 821–835 (2009).

    Article  Google Scholar 

  54. Voss, M. W. et al. Aging brain from a network science perspective: something to be positive about? PLoS ONE 8, e78345 (2013).

    Article  CAS  Google Scholar 

  55. Craig, A. D. How do you feel—now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 (2009).

    Article  CAS  Google Scholar 

  56. Di Gangi Herms, A. M. et al. Functional imaging of stress urinary incontinence. Neuroimage 29, 267–275 (2006).

    Article  CAS  Google Scholar 

  57. Peters, K. M., Carrico, D. J., Wooldridge, L. S., Miller, C. J. & MacDiarmid, S. A. Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study. J. Urol. 189, 2194–2201 (2013).

    Article  Google Scholar 

  58. Chapple, C. R., Cardozo, L., Nitti, V. W., Siddiqui, E. & Michel, M. C. Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol. Urodyn. 33, 17–30 (2014).

    Article  CAS  Google Scholar 

  59. Mangera, A. et al. An updated systematic review and statistical comparison of standardised mean outcomes for the use of botulinum toxin in the management of lower urinary tract disorders. Eur. Urol. 65, 981–990 (2013).

    Article  Google Scholar 

  60. Andersson, K. E. & Yoshida, M. Antimuscarinics and the overactive detrusor—which is the main mechanism of action? Eur. Urol. 43, 1–5 (2003).

    Article  CAS  Google Scholar 

  61. Pontari, M. A. et al. Central nervous system findings on functional magnetic resonance imaging in patients before and after treatment with anticholinergic medication. J. Urol. 183, 1899–1905 (2010).

    Article  Google Scholar 

  62. Hafkemeijer, A., van der Grond, J. & Rombouts, S. A. Imaging the default mode network in aging and dementia. Biochim. Biophys. Acta 1822, 431–441 (2012).

    Article  CAS  Google Scholar 

  63. Krhut, J., Tintera, J., Holy, P., Zachoval, R. & Zvara, P. A preliminary report on the use of functional magnetic resonance imaging with simultaneous urodynamics to record brain activity during micturition. J. Urol. 188, 474–479 (2012).

    Article  Google Scholar 

  64. Michels, L. et al. Supraspinal control of urine storage and micturition in men-an fMRI study. Cereb. Cortex http://dx.doi.org/10.1093/cercor/bhu140 (2014).

  65. Barrington, F. J. The component reflexes of micturition in the cat. Part III. Brain 64, 239–243 (1941).

    Article  Google Scholar 

  66. Takasaki, A., Hui, M. & Sasaki, M. Is the periaqueductal gray an essential relay center for the micturition reflex pathway in the cat? Brain Res. 1317, 108–115 (2010).

    Article  CAS  Google Scholar 

  67. Matsuura, S., Allen, G. V. & Downie, J. W. Volume-evoked micturition reflex is mediated by the ventrolateral periaqueductal gray in anesthetized rats. Am. J. Physiol. 275, R2049–R2055 (1998).

    CAS  PubMed  Google Scholar 

  68. Tai, C. et al. Brain switch for reflex micturition control detected by FMRI in rats. J. Neurophysiol. 102, 2719–2730 (2009).

    Article  Google Scholar 

  69. Ongur, D. & Price, J. L. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex 10, 206–219 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author acknowledges the indispensable help of his colleagues, especially Dr Stasa Tadic, Dr Neil Resnick and Professor Clare Fowler, in developing—over many years—the ideas put forward in this Review.

Author information

Authors and Affiliations

  1. Division of Geriatric Medicine and Institute on Aging, University of Pittsburgh, Kaufmann Medical Building, Suite 500, 3471 Fifth Avenue, Pittsburgh, 15213, PA, USA

    Derek Griffiths

Authors
  1. Derek Griffiths
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Derek Griffiths.

Ethics declarations

Competing interests

D.G. declares that he has acted as a consultant for J & J and Laborie Medical.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Griffiths, D. Neural control of micturition in humans: a working model. Nat Rev Urol 12, 695–705 (2015). https://doi.org/10.1038/nrurol.2015.266

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2015.266

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing