Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder

Purpose Sacral neuromodulation is widely used for refractory overactive bladder; however, its mechanism of action remains unclear. This study aims to investigate real-time changes in brain activity and functional connectivity (FC) during neuromodulation in an overactive bladder (OAB) rat model using...

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Main Authors: Haoyu Sun, Yongheng Zhou, Qinggang Liu, Xing Li, Limin Liao
Format: Article
Language:English
Published: Korean Continence Society 2025-06-01
Series:International Neurourology Journal
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Online Access:http://einj.org/upload/pdf/inj-2448420-210.pdf
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author Haoyu Sun
Yongheng Zhou
Qinggang Liu
Xing Li
Limin Liao
author_facet Haoyu Sun
Yongheng Zhou
Qinggang Liu
Xing Li
Limin Liao
author_sort Haoyu Sun
collection DOAJ
description Purpose Sacral neuromodulation is widely used for refractory overactive bladder; however, its mechanism of action remains unclear. This study aims to investigate real-time changes in brain activity and functional connectivity (FC) during neuromodulation in an overactive bladder (OAB) rat model using functional magnetic resonance imaging. Methods Twelve female Sprague Dawley rats were implanted with fine bipolar electrodes adjacent to the L6 nerve root. Cystometry was performed on normal rats, acetic acid-induced OAB rats, and during spinal nerve stimulation (SNS) to confirm efficacy. Task-based functional magnetic resonance imaging (fMRI) was acquired using a 20-second rest-stimulus cycle, followed by T2-weighted anatomical imaging on a 9.4T MRI scanner. Comparative analyses examined changes in the amplitude of low-frequency fluctuations (ALFF) and FC between normal and OAB rats. Brain activity during SNS was further assessed using the general linear model (GLM) and FC analysis. Statistical significance was defined as P<0.05 (family-wise error–corrected). Results Compared with normal rats, OAB rats exhibited increased ALFF in the left prefrontal cortex, periaqueductal gray (PAG), and left primary somatosensory cortex. In addition, FC between the PAG and pons was enhanced (P=0.002). GLM analysis revealed that the left primary somatosensory cortex, left prefrontal cortex, corpus callosum, left secondary motor area, and right brainstem exhibited decreased activity during SNS (P<0.05). Significant FC changes were observed between several regions: the left cerebellum and left caudal zona incerta (P=0.024), right fasciculus retroflexus and left ventral orbital area (P=0.025), and between the pons and PAG (P=0.004). Seed-to-voxel analysis indicated altered FC between clusters identified in the GLM analysis and regions including the PAG, left cingulate area, left prefrontal cortex, left caudate putamen, and right granular insular cortex. Conclusions Our fMRI study identified several alterations in brain activity during SNS in rats. Specifically, activity in the left prefrontal cortex decreased during SNS, and FC between the PAG and pons was reduced. These changes may represent central mechanisms underlying sacral neuromodulation in OAB patients.
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spelling doaj-art-e7e5f6f22b0b43dc88ecbc1c103f0d642025-08-20T03:58:45ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312025-06-01292819110.5213/inj.2448420.2101163Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive BladderHaoyu Sun0Yongheng Zhou1Qinggang Liu2Xing Li3Limin Liao4 Department of Urology, China Rehabilitation Research Center, School of Rehabilitation of Capital Medical University, Beijing, China Department of Urology, China Rehabilitation Research Center, Beijing, China Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China Department of Urology, China Rehabilitation Research Center, School of Rehabilitation of Capital Medical University, Beijing, China Department of Urology, China Rehabilitation Research Center, School of Rehabilitation of Capital Medical University, Beijing, ChinaPurpose Sacral neuromodulation is widely used for refractory overactive bladder; however, its mechanism of action remains unclear. This study aims to investigate real-time changes in brain activity and functional connectivity (FC) during neuromodulation in an overactive bladder (OAB) rat model using functional magnetic resonance imaging. Methods Twelve female Sprague Dawley rats were implanted with fine bipolar electrodes adjacent to the L6 nerve root. Cystometry was performed on normal rats, acetic acid-induced OAB rats, and during spinal nerve stimulation (SNS) to confirm efficacy. Task-based functional magnetic resonance imaging (fMRI) was acquired using a 20-second rest-stimulus cycle, followed by T2-weighted anatomical imaging on a 9.4T MRI scanner. Comparative analyses examined changes in the amplitude of low-frequency fluctuations (ALFF) and FC between normal and OAB rats. Brain activity during SNS was further assessed using the general linear model (GLM) and FC analysis. Statistical significance was defined as P<0.05 (family-wise error–corrected). Results Compared with normal rats, OAB rats exhibited increased ALFF in the left prefrontal cortex, periaqueductal gray (PAG), and left primary somatosensory cortex. In addition, FC between the PAG and pons was enhanced (P=0.002). GLM analysis revealed that the left primary somatosensory cortex, left prefrontal cortex, corpus callosum, left secondary motor area, and right brainstem exhibited decreased activity during SNS (P<0.05). Significant FC changes were observed between several regions: the left cerebellum and left caudal zona incerta (P=0.024), right fasciculus retroflexus and left ventral orbital area (P=0.025), and between the pons and PAG (P=0.004). Seed-to-voxel analysis indicated altered FC between clusters identified in the GLM analysis and regions including the PAG, left cingulate area, left prefrontal cortex, left caudate putamen, and right granular insular cortex. Conclusions Our fMRI study identified several alterations in brain activity during SNS in rats. Specifically, activity in the left prefrontal cortex decreased during SNS, and FC between the PAG and pons was reduced. These changes may represent central mechanisms underlying sacral neuromodulation in OAB patients.http://einj.org/upload/pdf/inj-2448420-210.pdfspinal nerve stimulationsacral neuromodulationfunctional magnetic resonance imagingoveractive bladder
spellingShingle Haoyu Sun
Yongheng Zhou
Qinggang Liu
Xing Li
Limin Liao
Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder
International Neurourology Journal
spinal nerve stimulation
sacral neuromodulation
functional magnetic resonance imaging
overactive bladder
title Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder
title_full Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder
title_fullStr Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder
title_full_unstemmed Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder
title_short Changes in Brain Activity and Functional Connectivity During Spinal Nerve Stimulation in a Rat Model of Overactive Bladder
title_sort changes in brain activity and functional connectivity during spinal nerve stimulation in a rat model of overactive bladder
topic spinal nerve stimulation
sacral neuromodulation
functional magnetic resonance imaging
overactive bladder
url http://einj.org/upload/pdf/inj-2448420-210.pdf
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