Simultaneous EMG-fMRI during startle inhibition in monosymptomatic enuresis--an exploratory study

Evidence is growing that monosymptomatic enuresis (ME) is a maturational disorder of the central nervous system with a lack of arousal and lacking inhibition of the micturition reflex. Previous studies have shown a significant reduction of prepulse inhibition (PPI) of startle in children with enuresis. However, it is still unclear whether the abnormal PPI in enuresis is based on an inhibitory deficit at brainstem or cortical level. Nine children with ME and ten healthy children were investigated using simultaneous recording of EMG from the M. orbicularis oculi and functional MRI. The experimental paradigm consisted of acoustic startle stimulation, with startle-alone stimuli and prepulse-startle combinations. Functional MRI data were processed using multiple regression and parametric modulation with startle amplitudes as a parameter. Neither patients with enuresis nor healthy children revealed measurable PPI in the MRI scanner. Startle stimuli caused equal hemodynamic changes in the acoustic cortex, medial prefrontal and orbitofrontal cortex in both groups. The amplitude of startle correlated with more prominent BOLD signal changes in the anterior cingulate cortex in healthy subjects than in patients with ME. This pronounced frontal activation in healthy controls was related to the PPI condition, indicating that the prefrontal cortex of healthy children was activated more strongly to inhibit startle than in patients with ME. In conclusion, apart from the possibility that recordings of PPI inside the MRI scanner may be compromised by methodological problems, the results of this study suggest that high cortical control mechanisms at the prefrontal level are relevant for the pathogenesis of ME.