OBJECTIVES: To compare brain responses to peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) and transcutaneous tibial nerve stimulation (TTNS), two methods for treating overactive bladder (OAB), using functional magnetic resonance imaging (fMRI). The present study was not designed to compare their clinical efficacy. MATERIALS AND METHODS: This study included 32 healthy adult female volunteers (average age 38.3 years (range 22-73)). Brain MRI using 3 T scanner was performed during three 8-min blocks of alternating sequences. During each 8-min block, the protocol alternated between sham stimulation (30 s) and rest (30 s) for 8 repeats; then peroneal eTNM® stimulation (30 s) and rest (30 s) for 8 repeats; then, TTNS stimulation (30 s) and rest (30 s) for 8 repeats. Statistical analysis was performed at the individual level with a threshold of p = 0.05, family-wise error (FWE)-corrected. The resulting individual statistical maps were analyzed in group statistics using a one-sample t-test, p = 0.05 threshold, false discovery rate (FDR)-corrected. RESULTS: During peroneal eTNM®, TTNS, and sham stimulations, we recorded activation in the brainstem, bilateral posterior insula, bilateral precentral gyrus, bilateral postcentral gyrus, left transverse temporal gyrus, and right supramarginal gyrus. During both peroneal eTNM® and TTNS stimulations, but not sham stimulations, we recorded activation in the left cerebellum, right transverse temporal gyrus, right middle frontal gyrus, and right inferior frontal gyrus. Exclusively during peroneal eTNM® stimulation, we observed activation in the right cerebellum, right thalamus, bilateral basal ganglia, bilateral cingulate gyrus, right anterior insula, right central operculum, bilateral supplementary motor cortex, bilateral superior temporal gyrus, and left inferior frontal gyrus. CONCLUSIONS: Peroneal eTNM®, but not TTNS, induces the activation of brain structures that were previously implicated in neural control of the of bladder filling and play an important role in the ability to cope with urgency. The therapeutic effect of peroneal eTNM® could be exerted, at least in part, at the supraspinal level of neural control.

Department of Clinical Research Biomedical Laboratory and Research Unit of Urology University of Southern Denmark Odense Denmark

Department of Radiodiagnostics and Interventional Radiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Surgical Studies Ostrava University Ostrava Czech Republic

Department of Urology 1st Faculty of Medicine of Charles University and Thomayer Hospital Prague Czech Republic

Department of Urology 2nd Faculty of Medicine of Charles University and Motol University Hospital Prague Czech Republic

Department of Urology Erasmus Medical Center Rotterdam The Netherlands

Department of Urology Odense University Hospital Odense Denmark

Department of Urology University Hospital Ostrava Czech Republic

See more in PubMed

Abrams P, Cardozo L, Wagg A, Wein A, eds. Incontinence. 6th Edition. ICI-ICS. International Continence Society; 2017.

Staskin DR, Peters KM, MacDiarmid S, Shore N, de Groat WC. Percutaneous tibial nerve stimulation: a clinically and cost-effective addition to the overactive bladder algorithm of care. Curr Urol Rep. 2012;13(5):327-334.

Peters KM, MacDiarmid SA, Wooldridge LS, et al. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. 2009;182(3):1055-1061.

Daly CME, Loi L, Booth J, Saidan D, Guerrero K, Tyagi V. Self-management of overactive bladder at home using transcutaneous tibial nerve stimulation: a qualitative study of women's experiences. BMC Womens Health. 2021;21(1):374.

Krhut J, Rejchrt M, Slovak M, et al. Prospective, randomized, multicenter trial of peroneal electrical transcutaneous neuromodulation vs solifenacin in treatment-naïve patients with overactive bladder. J Urol. 2023;209(4):734-741.

Gajewski JB, Kanai AJ, Cardozo L, Ikeda Y, Zabbarova IV. Does our limited knowledge of the mechanisms of neural stimulation limit its benefits for patients with overactive bladder? ICI-RS 2013: mechanisms of neural stimulation. Neurourol Urodyn. 2014;33(5):618-621.

Finazzi-Agrò E, Rocchi C, Pachatz C, et al. Percutaneous tibial nerve stimulation produces effects on brain activity: study on the modifications of the long latency somatosensory evoked potentials. Neurourol Urodyn. 2009;28(4):320-324.

Amarenco G, Ismael SS, Even-Schneider A, et al. Urodynamic effect of acute transcutaneous posterior tibial nerve stimulation in overactive bladder. J Urol. 2003;169(6):2210-2215.

Kitta T, Mitsui T, Kanno Y, Chiba H, Moriya K, Shinohara N. Brain-bladder control network: the unsolved 21st century urological mystery. Int J Urol. 2015;22(4):342-348.

Zare A, Jahanshahi A, Rahnama'i MS, Schipper S, van Koeveringe GA. The role of the periaqueductal gray matter in lower urinary tract function. Mol Neurobiol. 2019;56(2):920-934.

Pang D, Gao Y, Liao L. Functional brain imaging and central control of the bladder in health and disease. Front Physiol. 2022;13:914963.

Clarkson BD, Karim HT, Griffiths DJ, Resnick NM. Functional connectivity of the brain in older women with urgency urinary incontinence. Neurourol Urodyn. 2018;37(8):2763-2775.

Drake MJ, Fowler CJ, Griffiths D, Mayer E, Paton JFR, Birder L. Neural control of the lower urinary and gastrointestinal tracts: supraspinal CNS mechanisms. Neurourol Urodyn. 2010;29(1):119-127.

Blok B. Brain activation during micturition in women. Brain. 1998;121(Pt 11):2033-2042.

Griffiths D. Neural control of micturition in humans: a working model. Nat Rev Urol. 2015;12(12):695-705.

Ketai LH, Komesu YM, Dodd AB, Rogers RG, Ling JM, Mayer AR. Urgency urinary incontinence and the interoceptive network: a functional magnetic resonance imaging study. Am J Obstet Gynecol. 2016;215(4):449.e1-449.e17.

Michels L, Blok BFM, Gregorini F, et al. Supraspinal control of urine storage and micturition in men-an fMRI study. Cerebral Cortex. 2015;25(10):3369-3380.

Mehnert U, Boy S, Svensson J, et al. Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve-an fMRI study in healthy women. Neuroimage. 2008;41(3):682-689.

Roy HA, Green AL. The central autonomic network and regulation of bladder function. Front Neurosci. 2019;13:535.

Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150(3699):971-979.

Sluka KA, Walsh D. Transcutaneous electrical nerve stimulation: basic science mechanisms and clinical effectiveness. J Pain. 2003;4(3):109-121.

Ramírez-García I, Blanco-Ratto L, Kauffmann S, Carralero-Martínez A, Sánchez E. Efficacy of transcutaneous stimulation of the posterior tibial nerve compared to percutaneous stimulation in idiopathic overactive bladder syndrome: randomized control trial. Neurourol Urodyn. 2019;38(1):261-268.

Te Dorsthorst M, van Balken M, Janssen D, Heesakkers J, Martens F. Real-life patient experiences of TTNS in the treatment of overactive bladder syndrome. Ther Adv Urol. 2021;Aug 31 13:175628722110414.

Gill BC, Pizarro-Berdichevsky J, Bhattacharyya PK, et al. Real-time changes in brain activity during sacral neuromodulation for overactive bladder. J Urol. 2017;198(6):1379-1385.

Blok BFM, Groen J, Bosch JLHR, Veltman DJ, Lammertsma AA. Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators. BJU Int. 2006;98(6):1238-1243.

The mechanism of action of neuromodulation in the treatment of overactive bladder