{"paper_id":"30793cf0-59b6-4a01-a792-6ed79b9deefb","body_text":"Multimodal Neuroimaging Insights into Central Mechanisms of Overactive Bladder with an Empty Bladder: A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Multimodal Neuroimaging Insights into Central Mechanisms of Overactive Bladder with an Empty Bladder: A Cross-Sectional Study Yangkun Feng, Yuwei Zhang, Deshui Yu, Huihui Song, Kaixin Zhang, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7175202/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and objective: Overactive bladder (OAB) is a complex condition involving central nervous system (CNS) processes that are not fully understood. We conducted a detailed neuroimaging study to investigate the CNS role in OAB, focusing on the bladder emptying phase. Methods This cross-sectional study included 168 OAB patients and 133 matched controls. Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) during the bladder emptying phase. Data were analyzed using tract-based spatial statistics (TBSS), graph theory, functional connectivity, and structure-function coupling. The Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire Short Form (OAB-q SF) were also utilized. Key findings and limitations TBSS revealed three white matter tracts with higher fractional anisotropy in OAB patients; the largest of these, including the body of the corpus callosum (bCC) and bilateral anterior corona radiata (ACR), correlated positively with OAB-q scores. Functional connectivity analysis indicated increased connectivity between the left dorsolateral superior frontal gyrus (SFGdor.L) and bilateral supplementary motor areas, and reduced connectivity between the left middle temporal gyrus (MTG.L) and the right inferior temporal gyrus (ITG.R). The left amygdala (AMYG.L) exhibited enhanced structure-function coupling, which was positively associated with OABSS and OAB-q scores. However, the study's cross-sectional design precludes determining causal relationships due to the lack of longitudinal data. Conclusions and clinical implications This study identified distinct functional and structural brain alterations in OAB patients during the bladder emptying phase. These findings offer new perspectives for investigating innovative treatment strategies. Overactive Bladder Central Nervous System Functional Neuroimaging Diffusion Tensor Imaging Diagnosis Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Overactive bladder (OAB) is a complex clinical syndrome characterized by urgency, frequent urination, and waking at night to urinate, known as nocturia. These symptoms may occur with or without urgency incontinence [ 1 ]. The condition often recurs even after treatment, causeing significant physical and emotional distress and placing a substantial burden on society. The central nervous system (CNS) plays a vital role in managing bladder function. It controls urine storage and release through a complex network of nerves [ 2 ]. For instance, the medial prefrontal cortex, hypothalamus, and pontine micturition center regulate urination. Key neurotransmitters, such as dopamine, 5-hydroxytryptamine, and acetylcholine, help maintain this delicate balance [ 3 ]. When the CNS does not work properly, it disrupts the functions of the brain, spinal cord, and peripheral nerves. This leads to urinary problems such as incontinence, retention, frequency, and urgency. Conditions like multiple sclerosis, spinal cord injuries, and cerebral palsy often trigger such problems [ 3 ]. In OAB, symptoms like urgency and detrusor overactivity are also linked to CNS issues, including abnormal brain activity, neurotransmitter imbalances, and impaired neural pathways [ 4 ]. These changes, along with other physical factors, highlight the complexity of OAB and the need for comprehensive treatments and focused research. Advanced brain imaging techniques have deepened our understanding of the neural mechanisms of OAB. Researchers now use tools like resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) to study the condition. Tadic et al. explored prefrontal cortical activities with blood oxygenation level dependent fMRI (BOLD-fMRI) [ 5 ]. Lai et al. analyzed changes in white matter microstructure alterations using DTI [ 6 ]. Mawla et al. identified distinct OAB subtypes by combining urgency ratings during natural bladder filling with functional MRI [ 7 ]. However, most prior studies focused on neuroimaging during bladder filling, capturing CNS changes specific to that state. While these findings are valuable, they may miss other key factors. For instance, urgency in OAB patients is not solely a matter of bladder capacity; it may also involve central sensitization [ 7 ]. Imaging done during bladder filling might partly hide changes related to central sensitization in these patients. Moreover, multimodal neuroimaging studies of OAB patients in empty bladder states have not yet been conducted, creating a significant gap in understanding the condition across different bladder states. This study used a multimodal neuroimaging approach, combining rs-fMRI and DTI, to investigate the neuroimaging characteristics during the bladder emptying phase in OAB patients. Using this data, we evaluated global functional connectivity patterns, white matter structural integrity, and graph theory-based brain network topology in OAB patients. Additionally, we investigated more subtle brain network abnormalities in OAB through structure-function coupling analysis. 2. Patients and methods 2.1. Study design This study was approved by the Institutional Ethics Board of Jiangnan University Medical Center (2024-Y-26) and registered with the Chinese Clinical Trial Registry (ChiCTR2400092006). All participants provided written informed consent. Eligible participants included Han Chinese, right-handed individuals aged > 18 years, with OAB patients diagnosed by two urologists per ICS guidelines and no recent (72 hours) use of anticholinergic drugs. Healthy controls were age-, sex-, and education level-matched volunteers from the hospital’s physical examination center. Exclusion criteria comprised pregnancy/lactation; prior genitourinary/reproductive tract surgery; severe systemic diseases or recent (3 months) anti-anxiety/antidepressant use; neurodegenerative disorders (e.g., Alzheimer’s or Parkinson’s disease); conditions potentially confounding urinary symptoms (e.g., vaginitis); MRI contraindications (e.g., metal implants); or T1-weighted imaging-evident brain abnormalities (e.g., infarction/vascular lesions). All participants fasted from fluids for 4 hours prior to MRI and demonstrated pre-/post-scan residual urine volumes < 20 mL (via bladder scan), ensuring standardized bladder emptiness during acquisition. 2.2. Clinical assessment OAB patients completed the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire Short Form (OAB-q SF). The OAB-q SF contains two validated subscales: the Symptom Bother scale (OAB-q SB; assessing symptom severity) and the Health-Related Quality of Life scale (OAB-q HRQL; evaluating life impact). Higher OAB-q SB scores indicate greater symptom severity, while lower OAB-q HRQL scores reflect poorer quality of life. 2.3. MRI examination MRI data were acquired using a Siemens Magnetom Vida 3.0T scanner with a 32-channel head coil. Before scanning, all subjects emptied their bladder and were instructed to remain awake and still. Head stabilization and noise reduction were achieved using sponge pads and earplugs. The specific MRI Imaging protocols and Data preprocessing are detailed in the Supplementary Data (Supplementary Methods Section). 2.4. Statistical analysis Statistical analyses were performed using SPSS (v25.0.1.0). The Kolmogorov-Smirnov test assessed the distribution of variables. Normally distributed variables were presented as mean ± SD and compared using two-tailed t-tests. Non-normally distributed variables were presented as median with interquartile range and analyzed using Mann-Whitney U tests. Chi-square tests compared categorical variables (e.g., gender) between the OAB and HC groups. Statistical analysis methods for TBSS and Network comparisons can be seen in the Supplementary Data (Supplementary Methods Section). 3. Results 3.1. Basic information of participants The flow chart of this study is shown in Fig. 1 . A total of 243 participants finally completed the study, comprising 119 patients with OAB (39 men, 80 women) and 124 healthy controls (37 men, 87 women). Both groups were well-matched on key demographic variables. Statistical analysis revealed no significant differences between groups in gender ratio, age, height, weight, or years of education ( Supplementary Table 1 ). This demographic comparability strengthens the validity of our between-group comparisons. Clinical assessments demonstrated clear differences between groups. OAB patients scored significantly higher on all symptom measures compared to healthy controls, including OABSS, OAB-q SB, and OAB-q HRQL ( Supplementary Table 1 ). These elevated scores confirm the presence of substantial urinary symptoms in the patient group. 3.2. Altered white matter fractional anisotropy in OAB patients TBSS analysis revealed three distinct white matter clusters in OAB patients characterized by significantly higher FA values compared to controls (Fig. 2 A). Cluster 1, spanning 121 voxels (peak MNI coordinates: -40, -37, -3), involved the left retroinsular cortex (RIC.L), left posterior thalamic radiation (PTR.L), and left suprasylvian area (SS.L). Cluster 2, containing 927 voxels (peak coordinates: -31, -68, 2), was localized to the left posterior thalamic radiation (PTR.L). Cluster 3, the most extensive distribution (33,937 voxels; peak coordinates: 23, -17, 36), encompassed multiple regions including the body of corpus callosum (bCC), bilateral anterior corona radiata (ACR.L/R), splenium of corpus callosum (sCC), right posterior thalamic radiation (PTR.R), and middle cerebellar peduncle (MCP), suggesting widespread structural involvement ( Supplementary Table 2 ). Further analysis of diffusion tensor metrics within these clusters identified additional differences between the groups. While MD values did not significantly differ between groups (Fig. 2 B), OAB patients showed significantly higher AD values in all three clusters (Fig. 2 C). Additionally, RD values were significantly lower in clusters 2 and 3 in the OAB group (Fig. 2 D). These combined findings suggest enhanced white matter fiber integrity or organization within these specific brain regions during the bladder emptying phase in OAB patients. Graph theory analysis of DTI data revealed a significantly increased normalized clustering coefficient (NCp) in the right superior temporal gyrus (STG.R) of OAB patients compared to healthy controls (FDR-corrected, P = 0.049) (Fig. 2 E), suggesting enhanced functional integration in this region. This localized alteration occurred despite no significant between-group differences in global network metrics (Sigma, Cp, Lp, Eg, Eloc, detailed in the Supplementary Data). Furthermore, no other local network measures, aside from the NCp in the STG.R, showed significant differences between the groups. 3.3. Altered whole-brain functional connectivity in OAB patients Whole-brain FC analysis identified three significantly altered functional connections in OAB patients (Fig. 3 A-C). Two connections showed enhanced connectivity in the OAB group: the functional connectivity between the left dorsal superior frontal gyrus (SFGdor.L) and the left supplementary motor area (SMA.L) was significantly strengthened (FDR correction, P = 0.016), as was connectivity between the SFGdor.L and the right supplementary motor area (SMA.R) (FDR correction, P = 0.010). The functional connection between the left middle frontal gyrus (MFG.L) and right inferior temporal gyrus (ITG.R) was markedly reduced in OAB patients (FDR correction, P = 0.012) (Fig. 3 D). 3.4. Altered structural-functional coupling in the amygdala of OAB patients Structure-function coupling analysis revealed no significant differences in global metrics between OAB patients and healthy controls (Fig. 4 A-B). However, an examination of local indices revealed that the left amygdala (AMYG.L) exhibited significantly higher structure-function coupling in OAB patients (FDR correction, P = 0.008) (Fig. 4 C). 3.5. Correlation between brain alterations and clinical symptoms in OAB patients Partial correlation analysis, controlling for age and gender, revealed significant associations between brain alterations and clinical symptoms (Table 1 ). Cluster 3 volume positively correlated with OAB-q scores ( R = 0.253, P = 0.047, FDR-corrected). Furthermore, enhanced structure-function coupling in the AMYG.L positively correlated with both OABSS scores ( R = 0.347, P = 0.003, FDR-corrected) and OAB-q scores ( R = 0.286, P = 0.021, FDR-corrected). Clinical measures did not significantly associate with the NCp in STG.R, SFGdor.L-SMA.L connectivity, SFGdor.L-SMA.R connectivity, or MFG.L-ITG.R connectivity. Table 1 Partial correlation among specific brain alterations and clinical symptoms in OAB patients. FA (cluster1) FA (cluster2) FA (cluster3) STG.R SFGdor.L-SMA.L SFGdor.L MFG.L AMYG.L -SMA.R -ITG.R OABSS score R -0.074 0.079 0.143 -0.035 0.058 0.005 0.158 0.347 P 0.425 0.396 0.125 0.708 0.533 0.955 0.088 0.000** Adjusted p 0.683 0.7311 0.375 0.894 0.8 0.955 0.352 0.003** OAB-q SB score R -0.048 0.143 0.225 -0.104 -0.024 0.024 0.074 0.286 P 0.611 0.123 0.015* 0.263 0.801 0.8 0.427 0.002** Adjusted p 0.815 0.422 0.07 0.631 0.915 0.96 0.683 0.021* OAB-q HRQL score R 0.054 0.141 0.253 -0.09 -0.023 -0.01 0.085 0.241 P 0.563 0.129 0.006** 0.334 0.808 0.916 0.363 0.009** Adjusted p 0.795 0.345 0.047* 0.728 0.882 0.956 0.727 0.051 OABSS: Overactive Bladder Symptom Score; OAB-q SB: the Symptom Bother scale; OAB-q HRQL: the Health-Related Quality of Life scale. * P < 0.05; ** P < 0.01. 4. Discussion This study employed a combined rs-fMRI and DTI approach to investigate neural alterations in OAB patients during bladder-emptying conditions. 4.1. White matter integrity changes Our study unexpectedly revealed significantly elevated FA values in key white matter regions of OAB patients, including the corpus callosum, corona radiata, and prethalamic radiation. This contrasts with previous reports that demonstrated decreased FA and increased MD in OAB populations [ 6 , 8 ]. It is important to note that our neuroimaging study was conducted during the bladder-emptying phase in OAB patients. Existing research has indicated that there were significant changes in the functional connectivity of the brain between full and empty bladders in healthy volunteers. Therefore, the divergence of our findings from other reported literature might stem from the focus of our study on the bladder-emptying state. Future research should further compare the differences across various bladder states, including different stages of filling and emptying, to gain a more comprehensive understanding. Notably, parallel findings appear in other chronic conditions. For instance, knee osteoarthritis patients show similar FA increases in comparable regions [ 9 ]. Additionally, patients with urologic chronic pelvic pain syndrome exhibit elevated FA in the right corticospinal tract and prethalamic radiation, which positively correlates with pain severity [ 10 ]. Of particular clinical significance, we found that FA values in the corpus callosum and corona radiata (Cluster 3) maintained a significant positive correlation with OAB symptom severity (OAB-q HRQL), even under bladder-emptying conditions. This suggests these white matter microstructural changes may represent stable neural characteristics of OAB, rather than transient effects of urinary urgency. These changes could potentially lead to sensitized bladder sensory signal processing and dysfunctional micturition reflex regulation, ultimately manifesting as core clinical symptoms of urinary frequency and urgency. 4.2. Regional structural network alterations Our DTI analysis revealed a significantly higher clustering coefficient in the STG.R of OAB patients compared to controls, while global network measures remained unchanged. This finding points to specific regional alterations rather than overall network disruption in OAB pathophysiology. The increased clustering in STG.R indicates enhanced local efficiency, suggesting either compensatory hyperconnectivity or altered information processing. The STG has not traditionally been considered a core component of the brain-bladder control network, which primarily includes the prefrontal cortex, cingulate gyrus, thalamus, basal ganglia, and insula [ 10 , 11 ]. However, several lines of evidence support its potential involvement in bladder function. Functional MRI studies show STG activation during micturition control [ 11 ], and research has reported reduced gray matter volume in the STG.R of OAB patients [ 10 ]. While primarily known for auditory and language processing [ 12 , 13 ], the role of STG in spatial awareness might extend to the perception of bladder sensation [ 14 ]. The right-hemisphere lateralization observed may reflect specific aspects of bladder signal processing [ 14 ], with heightened local efficiency possibly indicating altered responses to urgency signals. 4.3. Functional connectivity patterns Functional connectivity analysis revealed distinct neural communication patterns in OAB patients. They exhibit increased synchronicity between the SFGdor.L and the SMA. Previous studies have shown that OAB patients often display heightened connectivity between the SMA and brain regions associated with emotional processing [ 11 ]. This enhanced SFGdor.L-SMA connectivity may contribute to the emotional and cognitive amplification of urinary urgency symptoms. Furthermore, abnormal SMA activity or connectivity can disrupt the balance between sympathetic and parasympathetic outputs, potentially leading to autonomic imbalance. In contrast, OAB patients demonstrate reduced connectivity between the MFG.L and the ITG.R. This decreased connectivity might serve to mitigate information redundancy, potentially enhancing central network stability. Recent fMRI studies have identified additional alterations specific to female OAB patients, including decreased dynamic functional connectivity density in the ACC.L and mPFC.L [ 11 ]. These alterations across multiple brain networks showed that OAB involves complex neurological dysregulation beyond the bladder itself. 4.4. Structure-function coupling Structural connectivity (SC) is thought to shape and constrain functional connectivity (FC) across brain networks at various scales, while FC can influence SC through plasticity mechanisms [ 15 , 16 ]. Consequently, SC-FC coupling analysis has been proposed to study the association between SC and FC, demonstrating potential to detect more subtle brain abnormalities than single-modality approaches [ 17 – 20 ]. Our study found that the SC-FC coupling strength in the AMYG.L of OAB patients was enhanced and positively correlated with clinical symptoms (OABSS/OAB-q SB). This finding, consistent with the results of enhanced FA values in white matter tracts, suggests a specific neural remodeling pattern in OAB patients. The amygdala plays a crucial role in emotional processing and mediates between unconscious and conscious reactions to emotional events [ 21 ]. In bladder control, the amygdala may evaluate sensations associated with bladder filling and suppress urgency [ 22 ]. This finding aligns with research suggesting the amygdala could be part of a \"paralimbic circuit,\" potentially serving as a third mechanism in continence control beyond traditional brainstem switch and cortical inhibition pathways. The increased structure-function coupling in AMYG.L may imply enhanced functional connectivity with the prefrontal cortex, forming a \"hypersensitized\" emotional evaluation network [ 23 ]; and enhanced connectivity with the hypothalamus-brainstem pathway, potentially leading to autonomic dysregulation, ultimately affecting the autonomic nervous system's regulation of bladder function and causing urinary frequency and urgency. Several limitations should be considered when interpreting this study's findings. First, the cross-sectional design prevents definitive conclusions regarding causality between neural features and overactive bladder. Furthermore, while gender and education were accounted for, potential confounders like hypertension and diabetes were not addressed. The lack of longitudinal data also restricts our understanding of how white matter alterations progress over time. Future research employing longitudinal designs is essential to fully elucidate the dynamic neuroimaging changes and central regulatory pathways implicated in OAB. 5. Conclusions Our study employed multimodal neuroimaging techniques to further characterize central nervous system alterations in patients with OAB during the bladder emptying phase. Through comprehensive analysis of multiple neuroimaging parameters, we have supplemented existing evidence regarding the neural mechanisms underlying OAB, providing new insights into the central pathophysiological processes of this disorder. The identified neuroimaging signatures offer important clues for understanding the pathogenesis of OAB and may inform future clinical management strategies. Declarations Conflicts of interest The authors declare that they have no competing interests. Funding statement This study was supported by grants from Postgraduate Research & Practice Innovation Program of Jiangsu Province (no: SJCX25_1351 to YK.F.), the Wuxi City Science and Technology Innovation and Entrepreneurship Fund \"Taihu Light\" Science and Technology Research Program (no. Y20242111 to Y.H.), and the Top Talent Support Program for young and middleaged people of Wuxi Health Committee (no. HB2023035 to Y.H.). Statements and Declarations Data Availability statement The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Conflicts of interest The authors declare that they have no competing interests. Ethics approval statement This study was approved by the Institutional Ethics Board of Jiangnan University Medical Center (2024-Y-26). Patient consent statement All participants provided written informed consent. Permission to reproduce material from other sources Not applicable. Clinical trial registration This study was registered on the UK's Clinical Study Registry (ISRCTN11583354). References Nambiar AK, Arlandis S, Bo K, Cobussen-Boekhorst H, Costantini E, de Heide M et al (2022) European Association of Urology Guidelines on the Diagnosis and Management of Female Non-neurogenic Lower Urinary Tract Symptoms. Part 1: Diagnostics, Overactive Bladder, Stress Urinary Incontinence, and Mixed Urinary Incontinence. Eur Urol 82:49–59 Pang S, Yan J (2024) Research and progress on the mechanism of lower urinary tract neuromodulation: a literature review. PeerJ 12:e17870 Cho YS (2018) Importance of Central Regulation for Lower Urinary Tract Functions. Int Neurourol J 22:1 Smith AL, Berry A, Brubaker L, Cunningham SD, Gahagan S, Kane Low L et al (2024) The brain, gut, and bladder health nexus: A conceptual model linking stress and mental health disorders to overactive bladder in women. Neurourol Urodyn 43:424–436 Tadic SD, Griffiths D, Schaefer W, Murrin A, Clarkson B, Resnick NM (2012) Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol Urodyn 31:652–658 Lai HH, Rutlin J, Smith AR, Helmuth ME, Hokanson JA, Yang CC et al (2024) Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study. J Urol 212:351–361 Mawla I, Schrepf A, Kutch JJ, Helmuth ME, Smith AR, Ichesco E et al (2024) Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). J Urol 211:111–123 Zuo L, Tian T, Wang B, Gu H, Wang S (2024) Microstructural white matter abnormalities in overactive bladder syndrome evaluation with diffusion kurtosis imaging tract-based spatial statistics analysis. World J Urol 42:36 Cheng S, Dong X, Zhou J, Tang C, He W, Chen Y et al (2022) Alterations of the White Matter in Patients With Knee Osteoarthritis: A Diffusion Tensor Imaging Study With Tract-Based Spatial Statistics. Front Neurol 13:835050 Zuo L, Zhou Y, Wang S, Wang B, Gu H, Chen J (2021) Regional brain atrophy in overactive bladder syndrome: a voxel based morphometry study. Int Urol Nephrol 53:27–33 Biao W, Long Z, Yang Z, Hua G, Shuangkun W (2022) Abnormal resting-state brain activity and connectivity of brain-bladder control network in overactive bladder syndrome. Acta Radiol 63:1695–1702 Ramos Nunez AI, Yue Q, Pasalar S, Martin RC (2020) The role of left vs. right superior temporal gyrus in speech perception: An fMRI-guided TMS study. Brain Lang 209:104838 Liu L, Liu D, Guo T, Schwieter JW, Liu H (2023) The right superior temporal gyrus plays a role in semantic-rule learning: Evidence supporting a reinforcement learning model. NeuroImage 282:120393 Shah-Basak PP, Chen P, Caulfield K, Medina J, Hamilton RH (2018) The role of the right superior temporal gyrus in stimulus-centered spatial processing. Neuropsychologia 113:6–13 Hagmann P, Cammoun L, Gigandet X, Meuli R, Honey CJ, Wedeen VJ et al (2008) Mapping the structural core of human cerebral cortex. PLoS Biol 6:e159 Honey CJ, Sporns O, Cammoun L, Gigandet X, Thiran JP, Meuli R et al (2009) Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci U S A 106:2035–2040 Zhang R, Shao R, Xu G, Lu W, Zheng W, Miao Q et al (2019) Aberrant brain structural-functional connectivity coupling in euthymic bipolar disorder. Hum Brain Mapp 40:3452–3463 Zhang Z, Liao W, Chen H, Mantini D, Ding JR, Xu Q et al (2011) Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. Brain 134:2912–2928 Dai Z, Lin Q, Li T, Wang X, Yuan H, Yu X et al (2019) Disrupted structural and functional brain networks in Alzheimer's disease. Neurobiol Aging 75:71–82 Zhang J, Zhang Y, Wang L, Sang L, Yang J, Yan R et al (2017) Disrupted structural and functional connectivity networks in ischemic stroke patients. Neuroscience 364:212–225 Rus OG, Reess TJ, Wagner G, Zimmer C, Zaudig M, Koch K (2017) Functional and structural connectivity of the amygdala in obsessive-compulsive disorder. Neuroimage Clin 13:246–255 Kitta T, Mitsui T, Kanno Y, Chiba H, Moriya K, Shinohara N (2015) Brain-bladder control network: the unsolved 21st century urological mystery. Int J Urol 22:342–348 Gao J, Yang X, Chen X, Liu R, Wang P, Meng F et al (2021) Resting-state functional connectivity of the amygdala subregions in unmedicated patients with obsessive-compulsive disorder before and after cognitive behavioural therapy. J Psychiatry Neurosci 46:E628–E38 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7175202\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":505204072,\"identity\":\"bab9763a-e383-478a-8b9a-12b349f1fb31\",\"order_by\":0,\"name\":\"Yangkun Feng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yangkun\",\"middleName\":\"\",\"lastName\":\"Feng\",\"suffix\":\"\"},{\"id\":505204073,\"identity\":\"79501816-3c46-4b34-9889-76771b86cb4d\",\"order_by\":1,\"name\":\"Yuwei Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Medical School of Nantong University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yuwei\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":505204074,\"identity\":\"1740bdd2-63cc-4d65-8385-31ccb285143e\",\"order_by\":2,\"name\":\"Deshui Yu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Deshui\",\"middleName\":\"\",\"lastName\":\"Yu\",\"suffix\":\"\"},{\"id\":505204075,\"identity\":\"c572409b-4fcb-4b65-83ff-1a87614e1715\",\"order_by\":3,\"name\":\"Huihui Song\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Huihui\",\"middleName\":\"\",\"lastName\":\"Song\",\"suffix\":\"\"},{\"id\":505204076,\"identity\":\"dfb9e5de-0965-492f-86e3-baef32fc6187\",\"order_by\":4,\"name\":\"Kaixin Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kaixin\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":505204077,\"identity\":\"4e8531ec-00fb-498b-8357-d19116d2c94b\",\"order_by\":5,\"name\":\"Feng Lu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Feng\",\"middleName\":\"\",\"lastName\":\"Lu\",\"suffix\":\"\"},{\"id\":505204078,\"identity\":\"af597bd2-fa5e-4293-b5b9-1fc46415149b\",\"order_by\":6,\"name\":\"Xi Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xi\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":505204079,\"identity\":\"5176452e-c0b2-4c5e-88cc-aa89f699e4e6\",\"order_by\":7,\"name\":\"Xiuhong Hua\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiuhong\",\"middleName\":\"\",\"lastName\":\"Hua\",\"suffix\":\"\"},{\"id\":505204080,\"identity\":\"dbe8bf9c-f949-4566-8d05-806ef8e20637\",\"order_by\":8,\"name\":\"Siyi Fu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Siyi\",\"middleName\":\"\",\"lastName\":\"Fu\",\"suffix\":\"\"},{\"id\":505204081,\"identity\":\"632bc250-2f9d-413c-a492-ab454cfbcdff\",\"order_by\":9,\"name\":\"Jia Xu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jia\",\"middleName\":\"\",\"lastName\":\"Xu\",\"suffix\":\"\"},{\"id\":505204082,\"identity\":\"cd0c4ad4-e824-4d37-926d-e068432e030a\",\"order_by\":10,\"name\":\"Jianfeng Shao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jianfeng\",\"middleName\":\"\",\"lastName\":\"Shao\",\"suffix\":\"\"},{\"id\":505204083,\"identity\":\"1b2de3f3-0bfe-45b6-a15d-2b4b73ecc08e\",\"order_by\":11,\"name\":\"Yi Fan\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nanjing Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yi\",\"middleName\":\"\",\"lastName\":\"Fan\",\"suffix\":\"\"},{\"id\":505204084,\"identity\":\"cfb95438-5f16-42ef-9336-a3741dbe52d1\",\"order_by\":12,\"name\":\"Ye Hua\",\"email\":\"data:image/png;base64,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\",\"orcid\":\"\",\"institution\":\"Jiangnan University Medical Center\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Ye\",\"middleName\":\"\",\"lastName\":\"Hua\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-07-21 08:53:20\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-7175202/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-7175202/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":89984056,\"identity\":\"91b44806-07f3-48fb-83b0-f951954fef69\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:35:46\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":928093,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eThe flowchart of the present study.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7175202/v1/5239d89130b498d8d31dad79.png\"},{\"id\":89982089,\"identity\":\"b726fa04-724c-4586-bc76-fea23b96a13d\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:27:46\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":381822,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eSignificant differences in white matter structure between OAB patients and controls.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA. Distribution diagram of 3 cluster brain regions with significant changes in FA value in OAB patients through TBSS analysis. B-D. T-tests of the MD, AD, and RD values of the two groups. E. Distribution diagram of the STG.R brain region.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7175202/v1/e3847b736ef2ae778177669f.png\"},{\"id\":89982092,\"identity\":\"fd2b3ba5-c40f-44fa-8f12-06c0ae7af74f\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:27:46\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":606597,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eSignificant differences in functional brain connectivity between OAB patients and controls.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA-B. Whole brain functional connectivity analysis matrix. C. Schematic diagram of the 3 functional connections altered in OAB patients. D. Schematic diagram of OAB patient-specific brain functional connections.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7175202/v1/079615e959e3f9432fbec486.png\"},{\"id\":89984059,\"identity\":\"e5d73071-a798-490b-a243-0add7cd68cb0\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:35:46\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":495030,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eSignificant enhancement of structural-functional coupling in AMYG.L between OAB patients and controls.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA-B. Structure-function coupling matrix. C. Distribution diagram of the AMYG.L brain region.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7175202/v1/30091cd21a472155e3686113.png\"},{\"id\":91798666,\"identity\":\"4a54d484-9c73-49df-a8ab-10e6a07c3e83\",\"added_by\":\"auto\",\"created_at\":\"2025-09-21 17:46:30\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":3299292,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7175202/v1/0cf1afc0-c2de-4446-87df-27fde6dc8010.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Multimodal Neuroimaging Insights into Central Mechanisms of Overactive Bladder with an Empty Bladder: A Cross-Sectional Study\",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003eOveractive bladder (OAB) is a complex clinical syndrome characterized by urgency, frequent urination, and waking at night to urinate, known as nocturia. These symptoms may occur with or without urgency incontinence [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. The condition often recurs even after treatment, causeing significant physical and emotional distress and placing a substantial burden on society.\\u003c/p\\u003e\\u003cp\\u003eThe central nervous system (CNS) plays a vital role in managing bladder function. It controls urine storage and release through a complex network of nerves [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. For instance, the medial prefrontal cortex, hypothalamus, and pontine micturition center regulate urination. Key neurotransmitters, such as dopamine, 5-hydroxytryptamine, and acetylcholine, help maintain this delicate balance [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eWhen the CNS does not work properly, it disrupts the functions of the brain, spinal cord, and peripheral nerves. This leads to urinary problems such as incontinence, retention, frequency, and urgency. Conditions like multiple sclerosis, spinal cord injuries, and cerebral palsy often trigger such problems [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. In OAB, symptoms like urgency and detrusor overactivity are also linked to CNS issues, including abnormal brain activity, neurotransmitter imbalances, and impaired neural pathways [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. These changes, along with other physical factors, highlight the complexity of OAB and the need for comprehensive treatments and focused research.\\u003c/p\\u003e\\u003cp\\u003eAdvanced brain imaging techniques have deepened our understanding of the neural mechanisms of OAB. Researchers now use tools like resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) to study the condition. Tadic et al. explored prefrontal cortical activities with blood oxygenation level dependent fMRI (BOLD-fMRI) [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Lai et al. analyzed changes in white matter microstructure alterations using DTI [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Mawla et al. identified distinct OAB subtypes by combining urgency ratings during natural bladder filling with functional MRI [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. However, most prior studies focused on neuroimaging during bladder filling, capturing CNS changes specific to that state. While these findings are valuable, they may miss other key factors. For instance, urgency in OAB patients is not solely a matter of bladder capacity; it may also involve central sensitization [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Imaging done during bladder filling might partly hide changes related to central sensitization in these patients. Moreover, multimodal neuroimaging studies of OAB patients in empty bladder states have not yet been conducted, creating a significant gap in understanding the condition across different bladder states.\\u003c/p\\u003e\\u003cp\\u003eThis study used a multimodal neuroimaging approach, combining rs-fMRI and DTI, to investigate the neuroimaging characteristics during the bladder emptying phase in OAB patients. Using this data, we evaluated global functional connectivity patterns, white matter structural integrity, and graph theory-based brain network topology in OAB patients. Additionally, we investigated more subtle brain network abnormalities in OAB through structure-function coupling analysis.\\u003c/p\\u003e\"},{\"header\":\"2. Patients and methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.1. Study design\\u003c/h2\\u003e\\u003cp\\u003e This study was approved by the Institutional Ethics Board of Jiangnan University Medical Center (2024-Y-26) and registered with the Chinese Clinical Trial Registry (ChiCTR2400092006). All participants provided written informed consent. Eligible participants included Han Chinese, right-handed individuals aged\\u0026thinsp;\\u0026gt;\\u0026thinsp;18 years, with OAB patients diagnosed by two urologists per ICS guidelines and no recent (72 hours) use of anticholinergic drugs. Healthy controls were age-, sex-, and education level-matched volunteers from the hospital\\u0026rsquo;s physical examination center. Exclusion criteria comprised pregnancy/lactation; prior genitourinary/reproductive tract surgery; severe systemic diseases or recent (3 months) anti-anxiety/antidepressant use; neurodegenerative disorders (e.g., Alzheimer\\u0026rsquo;s or Parkinson\\u0026rsquo;s disease); conditions potentially confounding urinary symptoms (e.g., vaginitis); MRI contraindications (e.g., metal implants); or T1-weighted imaging-evident brain abnormalities (e.g., infarction/vascular lesions). All participants fasted from fluids for 4 hours prior to MRI and demonstrated pre-/post-scan residual urine volumes\\u0026thinsp;\\u0026lt;\\u0026thinsp;20 mL (via bladder scan), ensuring standardized bladder emptiness during acquisition.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.2. Clinical assessment\\u003c/h2\\u003e\\u003cp\\u003eOAB patients completed the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire Short Form (OAB-q SF). The OAB-q SF contains two validated subscales: the Symptom Bother scale (OAB-q SB; assessing symptom severity) and the Health-Related Quality of Life scale (OAB-q HRQL; evaluating life impact). Higher OAB-q SB scores indicate greater symptom severity, while lower OAB-q HRQL scores reflect poorer quality of life.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.3. MRI examination\\u003c/h2\\u003e\\u003cp\\u003eMRI data were acquired using a Siemens Magnetom Vida 3.0T scanner with a 32-channel head coil. Before scanning, all subjects emptied their bladder and were instructed to remain awake and still. Head stabilization and noise reduction were achieved using sponge pads and earplugs. The specific MRI Imaging protocols and Data preprocessing are detailed in the Supplementary Data (Supplementary Methods Section).\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.4. Statistical analysis\\u003c/h2\\u003e\\u003cp\\u003eStatistical analyses were performed using SPSS (v25.0.1.0). The Kolmogorov-Smirnov test assessed the distribution of variables. Normally distributed variables were presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD and compared using two-tailed t-tests. Non-normally distributed variables were presented as median with interquartile range and analyzed using Mann-Whitney U tests. Chi-square tests compared categorical variables (e.g., gender) between the OAB and HC groups. Statistical analysis methods for TBSS and Network comparisons can be seen in the Supplementary Data (Supplementary Methods Section).\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e3.1. Basic information of participants\\u003c/h2\\u003e\\u003cp\\u003eThe flow chart of this study is shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. A total of 243 participants finally completed the study, comprising 119 patients with OAB (39 men, 80 women) and 124 healthy controls (37 men, 87 women). Both groups were well-matched on key demographic variables. Statistical analysis revealed no significant differences between groups in gender ratio, age, height, weight, or years of education (\\u003cb\\u003eSupplementary Table\\u0026nbsp;1\\u003c/b\\u003e). This demographic comparability strengthens the validity of our between-group comparisons.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003eClinical assessments demonstrated clear differences between groups. OAB patients scored significantly higher on all symptom measures compared to healthy controls, including OABSS, OAB-q SB, and OAB-q HRQL (\\u003cb\\u003eSupplementary Table\\u0026nbsp;1\\u003c/b\\u003e). These elevated scores confirm the presence of substantial urinary symptoms in the patient group.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e3.2. Altered white matter fractional anisotropy in OAB patients\\u003c/h2\\u003e\\u003cp\\u003eTBSS analysis revealed three distinct white matter clusters in OAB patients characterized by significantly higher FA values compared to controls (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eA). Cluster 1, spanning 121 voxels (peak MNI coordinates: -40, -37, -3), involved the left retroinsular cortex (RIC.L), left posterior thalamic radiation (PTR.L), and left suprasylvian area (SS.L). Cluster 2, containing 927 voxels (peak coordinates: -31, -68, 2), was localized to the left posterior thalamic radiation (PTR.L). Cluster 3, the most extensive distribution (33,937 voxels; peak coordinates: 23, -17, 36), encompassed multiple regions including the body of corpus callosum (bCC), bilateral anterior corona radiata (ACR.L/R), splenium of corpus callosum (sCC), right posterior thalamic radiation (PTR.R), and middle cerebellar peduncle (MCP), suggesting widespread structural involvement (\\u003cb\\u003eSupplementary Table\\u0026nbsp;2\\u003c/b\\u003e).\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003eFurther analysis of diffusion tensor metrics within these clusters identified additional differences between the groups. While MD values did not significantly differ between groups (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eB), OAB patients showed significantly higher AD values in all three clusters (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eC). Additionally, RD values were significantly lower in clusters 2 and 3 in the OAB group (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eD). These combined findings suggest enhanced white matter fiber integrity or organization within these specific brain regions during the bladder emptying phase in OAB patients.\\u003c/p\\u003e\\u003cp\\u003eGraph theory analysis of DTI data revealed a significantly increased normalized clustering coefficient (NCp) in the right superior temporal gyrus (STG.R) of OAB patients compared to healthy controls (FDR-corrected, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.049) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eE), suggesting enhanced functional integration in this region. This localized alteration occurred despite no significant between-group differences in global network metrics (Sigma, Cp, Lp, Eg, Eloc, detailed in the Supplementary Data). Furthermore, no other local network measures, aside from the NCp in the STG.R, showed significant differences between the groups.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e3.3. Altered whole-brain functional connectivity in OAB patients\\u003c/h2\\u003e\\u003cp\\u003eWhole-brain FC analysis identified three significantly altered functional connections in OAB patients (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eA-C). Two connections showed enhanced connectivity in the OAB group: the functional connectivity between the left dorsal superior frontal gyrus (SFGdor.L) and the left supplementary motor area (SMA.L) was significantly strengthened (FDR correction, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.016), as was connectivity between the SFGdor.L and the right supplementary motor area (SMA.R) (FDR correction, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.010). The functional connection between the left middle frontal gyrus (MFG.L) and right inferior temporal gyrus (ITG.R) was markedly reduced in OAB patients (FDR correction, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.012) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eD).\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e3.4. Altered structural-functional coupling in the amygdala of OAB patients\\u003c/h2\\u003e\\u003cp\\u003eStructure-function coupling analysis revealed no significant differences in global metrics between OAB patients and healthy controls (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eA-B). However, an examination of local indices revealed that the left amygdala (AMYG.L) exhibited significantly higher structure-function coupling in OAB patients (FDR correction, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.008) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eC).\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e3.5. Correlation between brain alterations and clinical symptoms in OAB patients\\u003c/h2\\u003e\\u003cp\\u003ePartial correlation analysis, controlling for age and gender, revealed significant associations between brain alterations and clinical symptoms (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Cluster 3 volume positively correlated with OAB-q scores (\\u003cem\\u003eR\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.253, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.047, FDR-corrected). Furthermore, enhanced structure-function coupling in the AMYG.L positively correlated with both OABSS scores (\\u003cem\\u003eR\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.347, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.003, FDR-corrected) and OAB-q scores (\\u003cem\\u003eR\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.286, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.021, FDR-corrected). Clinical measures did not significantly associate with the NCp in STG.R, SFGdor.L-SMA.L connectivity, SFGdor.L-SMA.R connectivity, or MFG.L-ITG.R connectivity.\\u003c/p\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003ePartial correlation among specific brain alterations and clinical symptoms in OAB patients.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"10\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c9\\\" colnum=\\\"9\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c10\\\" colnum=\\\"10\\\"\\u003e\\u003c/div\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eFA (cluster1)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eFA (cluster2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eFA (cluster3)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eSTG.R\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eSFGdor.L-SMA.L\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003eSFGdor.L\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003eMFG.L\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eAMYG.L\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e-SMA.R\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e-ITG.R\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u003cp\\u003eOABSS score\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eR\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e-0.074\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.079\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.143\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e-0.035\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.058\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.005\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.158\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.347\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.425\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.396\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.125\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.708\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.533\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.955\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.088\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.000**\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eAdjusted p\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.683\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.7311\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.375\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.894\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.955\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.352\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.003**\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u003cp\\u003eOAB-q SB score\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eR\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e-0.048\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.143\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.225\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e-0.104\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e-0.024\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.024\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.074\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.286\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.611\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.123\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.015*\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.263\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.801\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.427\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.002**\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eAdjusted p\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.815\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.422\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.07\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.631\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.915\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.96\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.683\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.021*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u003cp\\u003eOAB-q HRQL score\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eR\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.054\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.141\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.253\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e-0.09\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e-0.023\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e-0.01\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.085\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.241\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.563\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.129\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.006**\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.334\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.808\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.916\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.363\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.009**\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cem\\u003eAdjusted p\\u003c/em\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.795\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.345\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.047*\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.728\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e0.882\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0.956\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.727\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e0.051\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003ctfoot\\u003e\\u003ctr\\u003e\\u003ctd colspan=\\\"10\\\"\\u003eOABSS: Overactive Bladder Symptom Score; OAB-q SB: the Symptom Bother scale; OAB-q HRQL: the Health-Related Quality of Life scale. \\u003csup\\u003e*\\u003c/sup\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05;\\u003csup\\u003e**\\u003c/sup\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01.\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tfoot\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eThis study employed a combined rs-fMRI and DTI approach to investigate neural alterations in OAB patients during bladder-emptying conditions.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e4.1. White matter integrity changes\\u003c/h2\\u003e\\u003cp\\u003eOur study unexpectedly revealed significantly elevated FA values in key white matter regions of OAB patients, including the corpus callosum, corona radiata, and prethalamic radiation. This contrasts with previous reports that demonstrated decreased FA and increased MD in OAB populations [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. It is important to note that our neuroimaging study was conducted during the bladder-emptying phase in OAB patients. Existing research has indicated that there were significant changes in the functional connectivity of the brain between full and empty bladders in healthy volunteers. Therefore, the divergence of our findings from other reported literature might stem from the focus of our study on the bladder-emptying state. Future research should further compare the differences across various bladder states, including different stages of filling and emptying, to gain a more comprehensive understanding.\\u003c/p\\u003e\\u003cp\\u003eNotably, parallel findings appear in other chronic conditions. For instance, knee osteoarthritis patients show similar FA increases in comparable regions [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Additionally, patients with urologic chronic pelvic pain syndrome exhibit elevated FA in the right corticospinal tract and prethalamic radiation, which positively correlates with pain severity [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. Of particular clinical significance, we found that FA values in the corpus callosum and corona radiata (Cluster 3) maintained a significant positive correlation with OAB symptom severity (OAB-q HRQL), even under bladder-emptying conditions. This suggests these white matter microstructural changes may represent stable neural characteristics of OAB, rather than transient effects of urinary urgency. These changes could potentially lead to sensitized bladder sensory signal processing and dysfunctional micturition reflex regulation, ultimately manifesting as core clinical symptoms of urinary frequency and urgency.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec15\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e4.2. Regional structural network alterations\\u003c/h2\\u003e\\u003cp\\u003eOur DTI analysis revealed a significantly higher clustering coefficient in the STG.R of OAB patients compared to controls, while global network measures remained unchanged. This finding points to specific regional alterations rather than overall network disruption in OAB pathophysiology. The increased clustering in STG.R indicates enhanced local efficiency, suggesting either compensatory hyperconnectivity or altered information processing.\\u003c/p\\u003e\\u003cp\\u003eThe STG has not traditionally been considered a core component of the brain-bladder control network, which primarily includes the prefrontal cortex, cingulate gyrus, thalamus, basal ganglia, and insula [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. However, several lines of evidence support its potential involvement in bladder function. Functional MRI studies show STG activation during micturition control [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e], and research has reported reduced gray matter volume in the STG.R of OAB patients [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. While primarily known for auditory and language processing [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e], the role of STG in spatial awareness might extend to the perception of bladder sensation [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. The right-hemisphere lateralization observed may reflect specific aspects of bladder signal processing [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e], with heightened local efficiency possibly indicating altered responses to urgency signals.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec16\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e4.3. Functional connectivity patterns\\u003c/h2\\u003e\\u003cp\\u003eFunctional connectivity analysis revealed distinct neural communication patterns in OAB patients. They exhibit increased synchronicity between the SFGdor.L and the SMA. Previous studies have shown that OAB patients often display heightened connectivity between the SMA and brain regions associated with emotional processing [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. This enhanced SFGdor.L-SMA connectivity may contribute to the emotional and cognitive amplification of urinary urgency symptoms. Furthermore, abnormal SMA activity or connectivity can disrupt the balance between sympathetic and parasympathetic outputs, potentially leading to autonomic imbalance.\\u003c/p\\u003e\\u003cp\\u003eIn contrast, OAB patients demonstrate reduced connectivity between the MFG.L and the ITG.R. This decreased connectivity might serve to mitigate information redundancy, potentially enhancing central network stability. Recent fMRI studies have identified additional alterations specific to female OAB patients, including decreased dynamic functional connectivity density in the ACC.L and mPFC.L [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. These alterations across multiple brain networks showed that OAB involves complex neurological dysregulation beyond the bladder itself.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec17\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e4.4. Structure-function coupling\\u003c/h2\\u003e\\u003cp\\u003eStructural connectivity (SC) is thought to shape and constrain functional connectivity (FC) across brain networks at various scales, while FC can influence SC through plasticity mechanisms [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. Consequently, SC-FC coupling analysis has been proposed to study the association between SC and FC, demonstrating potential to detect more subtle brain abnormalities than single-modality approaches [\\u003cspan additionalcitationids=\\\"CR18 CR19\\\" citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. Our study found that the SC-FC coupling strength in the AMYG.L of OAB patients was enhanced and positively correlated with clinical symptoms (OABSS/OAB-q SB). This finding, consistent with the results of enhanced FA values in white matter tracts, suggests a specific neural remodeling pattern in OAB patients. The amygdala plays a crucial role in emotional processing and mediates between unconscious and conscious reactions to emotional events [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. In bladder control, the amygdala may evaluate sensations associated with bladder filling and suppress urgency [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. This finding aligns with research suggesting the amygdala could be part of a \\\"paralimbic circuit,\\\" potentially serving as a third mechanism in continence control beyond traditional brainstem switch and cortical inhibition pathways. The increased structure-function coupling in AMYG.L may imply enhanced functional connectivity with the prefrontal cortex, forming a \\\"hypersensitized\\\" emotional evaluation network [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]; and enhanced connectivity with the hypothalamus-brainstem pathway, potentially leading to autonomic dysregulation, ultimately affecting the autonomic nervous system's regulation of bladder function and causing urinary frequency and urgency.\\u003c/p\\u003e\\u003cp\\u003eSeveral limitations should be considered when interpreting this study's findings. First, the cross-sectional design prevents definitive conclusions regarding causality between neural features and overactive bladder. Furthermore, while gender and education were accounted for, potential confounders like hypertension and diabetes were not addressed. The lack of longitudinal data also restricts our understanding of how white matter alterations progress over time. Future research employing longitudinal designs is essential to fully elucidate the dynamic neuroimaging changes and central regulatory pathways implicated in OAB.\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"5. Conclusions\",\"content\":\"\\u003cp\\u003eOur study employed multimodal neuroimaging techniques to further characterize central nervous system alterations in patients with OAB during the bladder emptying phase. Through comprehensive analysis of multiple neuroimaging parameters, we have supplemented existing evidence regarding the neural mechanisms underlying OAB, providing new insights into the central pathophysiological processes of this disorder. The identified neuroimaging signatures offer important clues for understanding the pathogenesis of OAB and may inform future clinical management strategies.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConflicts of interest\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eFunding statement\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study was supported by grants from Postgraduate Research \\u0026amp; Practice Innovation Program of Jiangsu Province (no: SJCX25_1351 to YK.F.), the Wuxi City Science and Technology Innovation and Entrepreneurship Fund \\\"Taihu Light\\\" Science and Technology Research Program (no. Y20242111 to Y.H.), and the Top Talent Support Program for young and middleaged people of Wuxi Health Committee (no. HB2023035 to Y.H.).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStatements and Declarations\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eData Availability statement\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConflicts of interest\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eEthics approval statement\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study was approved by the Institutional Ethics Board of Jiangnan University Medical Center (2024-Y-26).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003ePatient consent statement\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll participants provided written informed consent.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003ePermission to reproduce material from other sources\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eClinical trial registration\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study was registered on the UK's Clinical Study Registry (ISRCTN11583354).\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eNambiar AK, Arlandis S, Bo K, Cobussen-Boekhorst H, Costantini E, de Heide M et al (2022) European Association of Urology Guidelines on the Diagnosis and Management of Female Non-neurogenic Lower Urinary Tract Symptoms. Part 1: Diagnostics, Overactive Bladder, Stress Urinary Incontinence, and Mixed Urinary Incontinence. Eur Urol 82:49\\u0026ndash;59\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003ePang S, Yan J (2024) Research and progress on the mechanism of lower urinary tract neuromodulation: a literature review. PeerJ 12:e17870\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eCho YS (2018) Importance of Central Regulation for Lower Urinary Tract Functions. Int Neurourol J 22:1\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eSmith AL, Berry A, Brubaker L, Cunningham SD, Gahagan S, Kane Low L et al (2024) The brain, gut, and bladder health nexus: A conceptual model linking stress and mental health disorders to overactive bladder in women. Neurourol Urodyn 43:424\\u0026ndash;436\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eTadic SD, Griffiths D, Schaefer W, Murrin A, Clarkson B, Resnick NM (2012) Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol Urodyn 31:652\\u0026ndash;658\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eLai HH, Rutlin J, Smith AR, Helmuth ME, Hokanson JA, Yang CC et al (2024) Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study. J Urol 212:351\\u0026ndash;361\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMawla I, Schrepf A, Kutch JJ, Helmuth ME, Smith AR, Ichesco E et al (2024) Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). J Urol 211:111\\u0026ndash;123\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZuo L, Tian T, Wang B, Gu H, Wang S (2024) Microstructural white matter abnormalities in overactive bladder syndrome evaluation with diffusion kurtosis imaging tract-based spatial statistics analysis. World J Urol 42:36\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eCheng S, Dong X, Zhou J, Tang C, He W, Chen Y et al (2022) Alterations of the White Matter in Patients With Knee Osteoarthritis: A Diffusion Tensor Imaging Study With Tract-Based Spatial Statistics. Front Neurol 13:835050\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZuo L, Zhou Y, Wang S, Wang B, Gu H, Chen J (2021) Regional brain atrophy in overactive bladder syndrome: a voxel based morphometry study. Int Urol Nephrol 53:27\\u0026ndash;33\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eBiao W, Long Z, Yang Z, Hua G, Shuangkun W (2022) Abnormal resting-state brain activity and connectivity of brain-bladder control network in overactive bladder syndrome. Acta Radiol 63:1695\\u0026ndash;1702\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eRamos Nunez AI, Yue Q, Pasalar S, Martin RC (2020) The role of left vs. right superior temporal gyrus in speech perception: An fMRI-guided TMS study. Brain Lang 209:104838\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eLiu L, Liu D, Guo T, Schwieter JW, Liu H (2023) The right superior temporal gyrus plays a role in semantic-rule learning: Evidence supporting a reinforcement learning model. NeuroImage 282:120393\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eShah-Basak PP, Chen P, Caulfield K, Medina J, Hamilton RH (2018) The role of the right superior temporal gyrus in stimulus-centered spatial processing. Neuropsychologia 113:6\\u0026ndash;13\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHagmann P, Cammoun L, Gigandet X, Meuli R, Honey CJ, Wedeen VJ et al (2008) Mapping the structural core of human cerebral cortex. PLoS Biol 6:e159\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHoney CJ, Sporns O, Cammoun L, Gigandet X, Thiran JP, Meuli R et al (2009) Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci U S A 106:2035\\u0026ndash;2040\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZhang R, Shao R, Xu G, Lu W, Zheng W, Miao Q et al (2019) Aberrant brain structural-functional connectivity coupling in euthymic bipolar disorder. Hum Brain Mapp 40:3452\\u0026ndash;3463\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZhang Z, Liao W, Chen H, Mantini D, Ding JR, Xu Q et al (2011) Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. Brain 134:2912\\u0026ndash;2928\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eDai Z, Lin Q, Li T, Wang X, Yuan H, Yu X et al (2019) Disrupted structural and functional brain networks in Alzheimer's disease. Neurobiol Aging 75:71\\u0026ndash;82\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eZhang J, Zhang Y, Wang L, Sang L, Yang J, Yan R et al (2017) Disrupted structural and functional connectivity networks in ischemic stroke patients. Neuroscience 364:212\\u0026ndash;225\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eRus OG, Reess TJ, Wagner G, Zimmer C, Zaudig M, Koch K (2017) Functional and structural connectivity of the amygdala in obsessive-compulsive disorder. Neuroimage Clin 13:246\\u0026ndash;255\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eKitta T, Mitsui T, Kanno Y, Chiba H, Moriya K, Shinohara N (2015) Brain-bladder control network: the unsolved 21st century urological mystery. Int J Urol 22:342\\u0026ndash;348\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eGao J, Yang X, Chen X, Liu R, Wang P, Meng F et al (2021) Resting-state functional connectivity of the amygdala subregions in unmedicated patients with obsessive-compulsive disorder before and after cognitive behavioural therapy. J Psychiatry Neurosci 46:E628\\u0026ndash;E38\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Overactive Bladder, Central Nervous System, Functional Neuroimaging, Diffusion Tensor Imaging, Diagnosis\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7175202/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7175202/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground and objective:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eOveractive bladder (OAB) is a complex condition involving central nervous system (CNS) processes that are not fully understood. We conducted a detailed neuroimaging study to investigate the CNS role in OAB, focusing on the bladder emptying phase.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis cross-sectional study included 168 OAB patients and 133 matched controls. Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) during the bladder emptying phase. Data were analyzed using tract-based spatial statistics (TBSS), graph theory, functional connectivity, and structure-function coupling. The Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire Short Form (OAB-q SF) were also utilized.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eKey findings and limitations\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTBSS revealed three white matter tracts with higher fractional anisotropy in OAB patients; the largest of these, including the body of the corpus callosum (bCC) and bilateral anterior corona radiata (ACR), correlated positively with OAB-q scores. Functional connectivity analysis indicated increased connectivity between the left dorsolateral superior frontal gyrus (SFGdor.L) and bilateral supplementary motor areas, and reduced connectivity between the left middle temporal gyrus (MTG.L) and the right inferior temporal gyrus (ITG.R). The left amygdala (AMYG.L) exhibited enhanced structure-function coupling, which was positively associated with OABSS and OAB-q scores. However, the study's cross-sectional design precludes determining causal relationships due to the lack of longitudinal data.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions and clinical implications\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study identified distinct functional and structural brain alterations in OAB patients during the bladder emptying phase. These findings offer new perspectives for investigating innovative treatment strategies.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Multimodal Neuroimaging Insights into Central Mechanisms of Overactive Bladder with an Empty Bladder: A Cross-Sectional Study\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-08-27 06:27:41\",\"doi\":\"10.21203/rs.3.rs-7175202/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"d4de08ad-f47e-4136-b332-8b780d52fe27\",\"owner\":[],\"postedDate\":\"August 27th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-09-21T17:38:23+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-08-27 06:27:41\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7175202\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7175202\",\"identity\":\"rs-7175202\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}