Cortical substrate of bladder control in SCI and the effect of peripheral pudendal stimulation

We investigated (i) the central representation of lower urinary tract (LUT) control and (ii-iii) the acute and short-term central neuromodulatory effect of peripheral pudendal nerve stimulation in incomplete spinal cord injured (SCI) patients using functional magnetic resonance imaging (fMRI). The urinary bladder of eight SCI patients has been passively filled and emptied using a catheter, to identify the neural substrate of bladder control (i), and with simultaneous peripheral pudendal nerve stimulation to investigate its acute central neuromodulatory effect (ii). To identify the potential effects of pudendal nerve stimulation treatment (iii), six patients underwent a 2-week training using pudendal nerve stimulation followed by another fMRI session of bladder filling. The pre- and post-training fMRI results have been compared and correlated with the patient's pre- and post-training urological status. Our results suggest that the central representation of bladder filling sensation is preserved in the subacute stage of incomplete SCI. However, compared to earlier data from healthy subjects, it shows decreased neural response in right prefrontal areas and increased in left prefrontal regions, indicating diminished inhibitory micturition control as well as, compensatory or decompensatory reorganization of bladder control. We also provide evidence for a neuromodulatory effect of acute pudendal nerve stimulation, which was most prominent in the right posterior insula, a brain region implicated in homeostatic interoception in human. Pudendal stimulation training also induced significant neuromodulation, predominantly signal increases, in the normal cortical network of bladder control. Correlations with the patient's urological status indicate that this neuromodulatory effect may reflect the clinical improvement following training.