Abstract
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.
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Allen PJ, Josephs O, Turner R (2000) A method of removing imaging artifact from continuous EEG recorded during functional MRI. NeuroImage 12(2):230–239
Allen PJ, Polizzi G, Krakow K, Fish DR, Lernieux L (1998) Identification of EEG events in the MR scanner: the problem of pulse artifact and a method for its subtraction. NeuroImage 8(3):229–239
Buchel C, Holmes AP, Rees G, Friston KJ (1998) Characterizing stimulus-response functions using nonlinear regressors in parametric fMRI experiments. NeuroImage 8(2):140–148
Campbell LE, Hughes M, Budd TW, Cooper G, Fulham WR, Karayanidis F, Hanlon M-C, Stojanow W, Johnson P, Case V, Schall U (2007) Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response. Eur J Neurosci 26(8):2327–2333
Davies PL, Chang WP, Gavin WJ (2009) Maturation of sensory gating performance in children with and without sensory processing disorders. Int J Psychophysiol 72(2):187–197
Dillo W, Göke A, Prox-Vagedes V, Szycik GR, Roy M, Donnerstag F, Emrich HM, Ohlmeier MD (2010) Neuronal correlates of ADHD in adults with evidence for compensation strategies—a functional MRI study with a Go/No-Go paradigm. Ger Med Sci 8:Doc09
Eggert P, Fritz A, Stecker B, Müller D (2004) Desmopressin has an effect on the arousability of children with primary nocturnal enuresis. J Urol 171:2586–2588
Esposito F, Aragri A, Piccoli T, Tedeschi G, Goebel R, Di Salle F (2009) Distributed analysis of simultaneous EEG-fMRI time-series: modeling and interpretation issues. Magn Res Imaging 27(8):1120–1130
Evans AC, Collins DL, Mills SR, Brown ED, Kelly RL, Peters TM (1993) 3D statistical neuroanatomical models from 305 MRI volumes. Proc IEEE Nucl Sci Symp Med Imaging Conf 1993:1813–1817
Filion DL, Poje AB (1993) Selective and nonselective attention effects on prepulse inhibition of startle: a comparison of task and no-task protocols. Biol Psychol 64:283–296
Friston KJ, Holmes AP, Worsley KP, Poline JP, Frith CD, Frackowiak RSJ (1995) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Map 2:189–210
Goldman MB, Heidinger L, Kulkarni K, Zhu DC, Chien A, McLaren DG, Shah J, Coffrey CH, Sharif S, Chen E, Uftring SJ, Small SL, Solodkin A, Pilla RS (2006) Changes in the amplitude and timing of the hemodynamic response associated with prepulse inhibition of acoustic startle. NeuroImage 32(3):2375–1384
Hazlett EA, Buchsbaum MS, Tang CY, Fleischman MB, Wei T-C, Byne W, Hazdenar MM (2001) Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study. Biol Psychiatry 50(4):281–291
Hazlett EA, Dawson ME, Schell AM, Nuechterlein KH (2008) Probing attentional dysfunctions in schizophrenia: startle modification during a continuous performance test. Psychophysiology 45(4):632–642
Hyde TM, Deep-Soboslay A, Iglesias B, Callicott JH, Gold JM, Meyer-Lindenberg A, Honea RA, Bigelow LB, Egan MF, Emsellem EM, Weinberger DR (2008) Enuresis as a premorbid developmental marker of schizophrenia. Brain 131(9):2489–2498
Kavia RB, Dasgupta R, Fowler CJ (2005) Functional imaging and the central control of the bladder. J Comp Neurol 493(1):27–32
Kuhtz-Buschbeck JP, Gilster R, van der Horst C, Hamann M, Wolff S, Jansen O (2009) Control of bladder sensations: an fMRI study of brain activity and effective connectivity. NeuroImage 47:18–27
Kumari V, Antonova E, Geyer MA (2008) Prepulse inhibition and “psychosis-proneness” in healthy individuals: an fMRI study. Eur Psychiatry 23(4):274–280
Kumari V, Das M, Zachariah E, Ettinger U, Sharma T (2005) Reduced prepulse inhibition in unaffected siblings of schizophrenia patients. Psychophysiology 42(5):588–594
Kumari V, Gray JA, Geyer MA, Ffytche D, Soni W, Mitterschiffthaler MT, Vythelingum GN, Simmons A, Williams SC, Sharma T (2003) Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects. Psychiatry Res 122(2):99–113
Li L, Du Y, Li N, Wu X, Wu Y (2009) Top-down modulation of prepulse inhibition of the startle reflex in humans and rats. Neurosci Biobehav Rev 33(8):1157–1167
McDowell JE, Brown GG, Lazar N, Camchong J, Sharp R, Krebs-Thomson K, Eyler LT, Braff DL, Geyer MA (2006) The neural correlates of habituation of response to startling tactile stimuli presented in a functional magnetic resonance imaging environment. Neuroimaging 148(1):1–10
Neuner I, Stöcker T, Kellermann T, Ermer V, Wegener HP, Eickhoff SB, Schneider F, Shah NJ (2010) Electrophysiology meets fMRI: neural correlates of the startle reflex assessed by simultaneous EMG-fMRI data acquisition. Hum Brain Mapp 31(11):1675–1685
Neveus T, von Gontard A, Hoebeke P, Hjälmås K, Bauer S, Bower W, Jørgensen TM, Rittig S, Walle JV, Yeung CK, Djurhuus JC (2006) The standardization of terminology of lower urinary tract function in children and adolescents: report from the standardisation committee of the International Children’s Continence Society (ICCS). J Urol 176(1):314–324
Ornitz EM, Guthrie D, Dadeghpour M, Sugiyama T (1991) Maturation of prestimulation-induced startle modulation in girls. Psychophysiology 28(1):11–20
Ornitz EM, Guthrie D, Kaplan AR, Lane SJ, Norman RJ (1986) Maturation of startle modulation. Psychophysiology 23(6):624–634
Ornitz EM, Hanna G, Detraversay LJ (1992) Prestimulation-induced startle modulation in attention-deficit hyperactivity disorder and nocturnal enuresis. Psychophysiology 29(4):437–451
Ornitz EM, Russell AT, Hanna GL, Gabikian P, Gehricke JG, Song D, Guthrie D (1999) Prepulse inhibition of startle and the neurobiology of primary nocturnal enuresis. Biol Psychiatr 45(11):1455–1466
Picton TW, Stuss DT, Alexander MP, Shallice T, Binns MA, Gillingham S (2007) Effects of focal frontal lesions on response inhibition. Cereb Cortex 17(4):826–838
Pissiota A, Frans Ö, Frederikson M, Langstrom B, Flaten MA (2002) The human startle reflex and pons activation: a regional cerebral blood flow study. Eur J Neurosci 15(2):395–398
Posner MI, Rothbart MK, Sheese NE, Tang Y (2007) The anterior cingulate gyrus and the mechanism of self-regulation. Cogn Affect Behav Neurosci 7(4):391–395
Schulz-Juergensen S, Rieger M, Schaefer J, Neusuess A, Eggert P (2007) Effect of 1-desamino-8-D-arginine vasopressin on prepulse inhibition of startle supports a central etiology of primary monosymptomatic enuresis. J Pediatr 151(6):571–574
Swerdlow NR, Karban B, Ploum Y, Sharp R, Geyer MA, Eastvold A (2001) Tactile prepuff inhibition of startle in children with Tourette’s syndrome: in search of an “fMRI-friendly” startle paradigm. Biol Psychiatry 50(8):578–585
Acknowledgments
The authors declare to have received no funding from an external organization in the context of this study. They want to thank Dr. J. Aaron Baudhuin (Department for Psychosomatic Medicine, General Hospital Bad Segeberg, Bad Segeberg, Germany) for editorial revision of the manuscript. They also want to thank Dr. Friederike Moeller, PhD (Department of Neuropediatrics, University Hospital Schleswig-Holstein, Campus Kiel) for assistance and advice in the revision of the manuscript.
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Suppl. Fig. S1
Brain areas with correlations between startle amplitude and BOLD signal changes in healthy (a) and patient (b) group (p < 0.01 noncorrected) (JPEG 94 kb)
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Schulz-Juergensen, S., Wunberg, D., Wolff, S. et al. Simultaneous EMG–fMRI during startle inhibition in monosymptomatic enuresis—an exploratory study. Eur J Pediatr 172, 23–30 (2013). https://doi.org/10.1007/s00431-012-1829-y
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DOI: https://doi.org/10.1007/s00431-012-1829-y