Cerebral control of the lower urinary tract: How age-related changes might predispose to urge incontinence

Loss of bladder control (urge incontinence) is common in elderly; the cause is usually unknown. Functional imaging has revealed the brain network controlling responses to bladder filling. Age-related changes in this network might predispose to urge incontinence. We sought such changes in 10 continent, healthy women aged 30-79 years who underwent fMRI while fluid (approximately 20 ml) was repeatedly infused into and withdrawn from the bladder. Data were collected in 4 measurement blocks with progressively increasing bladder volumes and were analyzed by SPM2, using the contrast infuse-withdraw to quantify response to bladder infusion. Effective connectivity was examined by physiophysiological interaction (PhPI; see interpretation in Supplementary Material), with right insula (RI) and dorsal anterior cingulate cortex (dACC) as seed regions. Dependence on age and bladder volume (= block number) was assessed. Bladder infusion evoked expected activations. Activation decreased with age in bilateral insula and dACC. PhPI revealed connectivity with RI and dACC in regions that included bilateral putamen and R pontine micturition center. Interaction (connectivity) tended to increase with age in regions including L insula, L paracentral lobule and PAG. Consistent with a special role in maintaining continence, medial prefrontal cortex (mPFC) showed a trend to deactivation on bladder infusion that became more prominent in old age, and a trend to negative interaction (connectivity) that weakened significantly with age. Thus, with increasing age, weaker signals in the bladder control network as a whole and/or changes in mPFC function or connecting pathways may be responsible for the development of urge incontinence.

[1]  A. Craig,et al.  REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY Neuroimaging of the Brain-Gut Axis: From Basic Understanding to Treatment of Functional GI Disorders , 2006 .

[2]  A. Holmes Generalisability, random effects and population inference (abstract) , 1998 .

[3]  N. Resnick,et al.  The Effect of Age on Lower Urinary Tract Function: A Study in Women , 2006, Journal of the American Geriatrics Society.

[4]  M. Fall,et al.  The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. , 2002, American journal of obstetrics and gynecology.

[5]  Karl J. Friston,et al.  Statistical parametric mapping (SPM) , 2008, Scholarpedia.

[6]  Wolfgang Grodd,et al.  Functional imaging of stress urinary incontinence , 2006, NeuroImage.

[7]  R. Adolphs Social cognition and the human brain , 1999, Trends in Cognitive Sciences.

[8]  Armin Curt,et al.  An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction , 2005, NeuroImage.

[9]  Derek J. Griffiths,et al.  Abnormal connections in the supraspinal bladder control network in women with urge urinary incontinence , 2008, NeuroImage.

[10]  P. Nathan,et al.  LESIONS ON THE ANTERIOR FRONTAL LOBES AND DISTURBANCES OF MICTURITION AND DEFAECATION. , 1964, Brain : a journal of neurology.

[11]  T. Shallice,et al.  Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. , 2003, Brain : a journal of neurology.

[12]  N. Resnick,et al.  Brain control of normal and overactive bladder. , 2005, The Journal of urology.

[13]  Jürgen Baudewig,et al.  Voluntary pelvic floor muscle control—an fMRI study , 2006, NeuroImage.

[14]  D. Griffiths,et al.  Bladder control, urgency, and urge incontinence: Evidence from functional brain imaging , 2008, Neurourology and urodynamics.

[15]  Abraham Z. Snyder,et al.  A default mode of brain function: A brief history of an evolving idea , 2007, NeuroImage.

[16]  G. Holstege,et al.  A PET study on brain control of micturition in humans. , 1997, Brain : a journal of neurology.

[17]  W. C. Groat,et al.  The neural control of micturition , 2008, Nature Reviews Neuroscience.

[18]  D. Griffiths,et al.  Urinary incontinence in the elderly: the brain factor. , 1994, Scandinavian journal of urology and nephrology. Supplementum.

[19]  Derek J. Griffiths,et al.  Cerebral control of the bladder in normal and urge-incontinent women , 2007, NeuroImage.

[20]  Gert Holstege,et al.  The central nervous system control of micturition in cats and humans , 1998, Behavioural Brain Research.

[21]  S. Matsuura,et al.  Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. , 2002, The Journal of urology.

[22]  A. Nabavi,et al.  Cortical representation of the urge to void: a functional magnetic resonance imaging study. , 2005, The Journal of urology.

[23]  Karl J. Friston,et al.  Generalisability, Random Effects & Population Inference , 1998, NeuroImage.

[24]  C. Reynolds,et al.  A fully automated method for quantifying and localizing white matter hyperintensities on MR images , 2006, Psychiatry Research: Neuroimaging.