1 2 Brain Switch for Reflex Micturition Control 3 Detected by fMRI in Rats

45 The functions of the lower urinary tract are controlled by complex pathways in 46 the brain that act like switching circuits to voluntarily or reflexly shift the activity of 47 various pelvic organs (bladder, urethra, urethral sphincter and pelvic floor muscles) from 48 urine storage to micturition. In this study, functional MRI (fMRI) was employed to 49 visualize the brain switching circuits controlling reflex micturition in anesthetized rats. 50 The fMRI images confirmed the hypothesis based on previous neuroanatomical and 51 neurophysiological studies that the brainstem switch for reflex micturition control 52 involves both the periaqueductal gray (PAG) and the pontine micturition center (PMC). 53 During storage, the PAG was activated by afferent input from the urinary bladder while 54 the PMC was inactive. When bladder volume increased to the micturition threshold, the 55 switch from storage to micturition was associated with PMC activation and enhanced 56 PAG activity. A complex brain network that may regulate the brainstem micturition 57 switch and control storage and voiding was also identified. Storage was accompanied by 58 activation of the motor cortex, somatosensory cortex, cingulate cortex, retrosplenial 59 cortex, thalamus, putamen, insula, and septal nucleus. On the other hand micturition was 60 associated with: (1) increased activity of the motor cortex, thalamus, putamen, (2) a shift 61 in the locus of activity in the cingulate and insula and (3) the emergence of activity in the 62 hypothalamus, substantia nigra, globus pallidus, hippocampus and inferior colliculus. 63 Understanding brain control of reflex micturition is important for elucidating the 64 mechanisms underlying neurogenic bladder dysfunctions including frequency, urgency, 65 and incontinence. 66