Diagnostic Value of the Motor Band Sign in Amyotrophic Lateral Sclerosis: A 7T Magnetic Resonance Imaging Study

Diagnostic Value of the Motor Band Sign in Amyotrophic Lateral Sclerosis: A 7T Magnetic Resonance Imaging 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 Diagnostic Value of the Motor Band Sign in Amyotrophic Lateral Sclerosis: A 7T Magnetic Resonance Imaging Study Xunyan Huang, Zhe Zhang, Lin Chen, Shuo Yang, Xinyao Liu, Jingfeng Bi, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5726741/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jun, 2025 Read the published version in Translational Neurodegeneration → Version 1 posted 4 You are reading this latest preprint version Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons, with a median survival of 3–5 years [ 1 ]. The key challenge in diagnosis lies in the early detection of upper motor neuron (UMN) impairment, which mainly depends on clinical examination but can be obscured by severe lower motor neuron (LMN) impairment [ 2 ]. Consequently, searching for alternative UMN impairment markers has become a critical focus of ALS research. Recent magnetic resonance imaging (MRI) studies indicated a band-shaped low signal intensity along the primary motor cortex (M1), termed the motor band sign (MBS) [ 3 ]. MBS has emerged as an imaging marker for identifying UMN impairment in ALS [ 2 , 4 , 5 ]. Researchers believe this hypointensity results from ferritin accumulation within activated microglia in M1 [ 6 ]. SWI has demonstrated increased sensitivity in detecting subtle, uniformly distributed iron deposits, becoming the current mainstream modality for identifying MBS. However, there is currently a lack of reports of MBS in 7T SWI. Figures Figure 1 Main text To evaluate the diagnostic efficacy of the MBS in identifying UMN impairment via 7T SWI, this study prospectively recruited an ALS cohort at Beijing Tiantan Hospital between October 2021 and March 2023 (Fig. S1 ). All participants underwent standardized physical examinations, electromyography, and 7T MRI within a week. Quantitative assessment of MBS was performed using the motor band hypointensity ratio (MBHR, Fig. 1A), with details provided in Additional file 2 (The MBHR measurement protocol). The ALS cohort comprised 20 clinically definite ALS, 15 clinically probable ALS, 11 clinically probable laboratory-supported ALS, and 7 clinically possible ALS. Age- and gender-matched controls (n = 62) included 50 healthy controls (HCs) and 12 ALS mimic cases: 6 hereditary spastic paraplegia (HSP) patients and 6 LMN syndrome patients. Demographic and clinical characteristics are detailed in Table S1 . The results of group differences (Kruskal-Wallis H test, details in Additional file 2: Statistical analysis) revealed significant MBHR variations among ALS patients, ALS mimics, and HCs ( p < 0.0001; Fig. S2 A). Specifically, ALS patients exhibited lower MBHR compared to both ALS mimics ( p < 0.0001) and HCs ( p < 0.0001). Significant MBHR differences were also observed among ALS subgroups, ALS mimics, and HCs ( p < 0.0001; Fig. S2 B). Additionally, no correlation was observed between MBHR and age in the HC group (r = -0.08, p = 0.60; Fig. S3). Notably, we verified a significant MBHR-UMN impairment association in ALS (Fig. S4), confirming the potential of MBS as a promising neuroimaging biomarker for ALS UMN impairment. Moreover, receiver operating characteristic (ROC) analysis demonstrated the diagnostic performance of the MBS in differentiating clinically definite ALS patients from all controls (red line in Fig. 1B), where an MBHR cutoff of 54.6% yielded an area under the curve (AUC) of 0.930 (95% confidence interval [CI]: 0.828–1.000), with 90.0% sensitivity and 100% specificity. Application of this threshold revealed differential MBS prevalence across ALS diagnostic subgroups: 90.0% in clinically definite ALS, 73.3% in clinically probable ALS, 54.5% in clinically probable laboratory-supported ALS, and 42.9% in clinically possible ALS (Fig. 1C). Additionally, demographic and clinical characteristics of ALS subgroups with MBHR ≤ 54.6% and ROC analyses for other ALS subgroups are provided in Table S2 and Additional file 2 (Additional results), respectively. Clinically definite/probable ALS patients exhibited significantly higher MGH upper motor neuron scales (MGH UMNSs, p = 0.028) and lower revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) scores ( p = 0.027) compared to clinically probable laboratory-supported/possible ALS patients (Table S3). These functional differences may underlie the observed reduction in MBS prevalence in the latter groups. Additionally, comparative analysis revealed significantly faster disease progression in ALS patients versus ALS mimics ( p < 0.0001; Fig. 1G). Among ALS patients, those exhibiting the MBS demonstrated accelerated progression compared to MBS-negative cases ( p = 0.015; Fig. 1H). Furthermore, a strong negative correlation between MBHR and ΔFS was observed in ALS patients ( r = -0.51, p = 0.0006; Fig. 1I), whereas no significant association was observed in ALS mimics ( r = -0.33, p = 0.30; Fig. 1J). After excluding two outlier ALS patients with rapid progression, the significant association remained (Fig. S5). Conventional approaches for the MBS evaluation face challenges: subjective variability in visual assessments and technical limitations of quantitative methods (more details in Additional file 2: The MBHR measurement protocol). To overcome these limitations, our study adopted the adjacent subcortical white matter region as the reference standard, with two primary goals: enhancing clinical practicality through simplified protocol implementation and mitigating artifacts caused by 7T magnetic field inhomogeneities. This optimized SWI protocol demonstrated high interobserver consistency (Additional file 2: Intergroup consistency). Such results revealed a progressive decline in diagnostic sensitivity across ALS subgroups, paralleling reductions in diagnostic accuracy. Clinically probable laboratory-supported/possible ALS patients demonstrated significantly higher ALSFRS-R scores compared to clinically definite/probable ALS patients, suggesting earlier disease stages. These subgroups also exhibited milder UMN impairment, further indicating the MBS as a biomarker correlating with advanced disease burden and UMN degeneration severity. Although MBS detection is lower in these patients, a positive MBS can greatly boost diagnostic confidence. Integrating MBS as an additional UMN marker may accelerate diagnosis in ambiguous cases. For early-stage patients testing MBS-negative, follow-up MRI scans during disease progression could improve detection. In a subset of eight ALS patients who have clinical 3T MRI data available, 7T SWI demonstrated superior MBS detection rates (7/8 vs. 4/8 with 3T SWI) and provided enhanced visualization of lesion internal architecture (Figs. S6-S7). The study revealed that some ALS patients demonstrated an explicit stratified pattern on 7T SWI. We observed three layers (white rhomboids) between the hyperintense superficial grey matter layers (yellow arrowheads) and the grey-white matter junction (white arrowheads) in M1 in healthy controls as well as ALS mimics (Fig. 1D-E). In ALS patients, the signal intensity of the superficial and the deep layers in these three layers decreased, resulting in an Oreo-fashioned (dark-bright-dark) layered MBS (Fig. 1F). Detailed MBS images from all ALS patients are provided in Figs. S8-S10. Recent functional MRI (fMRI) studies have confirmed laminar-specific cortical activation patterns in humans [ 7 ], coinciding with histological evidence of ferritin-rich microglia predominantly localized in the middle and deep layers of the M1 [ 6 ]. Our findings suggest that the observed Oreo-fashioned layered MBS may reflect the cytoarchitecture organization of M1. However, Northall et al. reported predominant iron deposition in M1 layer VI (deepest cortical layer) in ALS patients [ 8 ]. The lack of SWI data and heterogeneous grouping of MBS-positive/negative cohorts might explain this discrepancy. Therefore, future research integrating submillimeter ultra-high-field MRI, iron-sensitive imaging, and disease pathology is necessary to further understand the layer-specific pathological features of ALS. The identification of disease progression biomarkers is critical for managing and treating ALS. Our findings supported accelerated progress in ALS patients with MBS and a strong inverse correlation between MBHR and ΔFS. Thus, we deduced that the MBS strongly correlated with the disease progression, warranting more consideration in clinical practice. There are several limitations in this study. The small sample size of ALS patients and disease controls limits the generalization of the above results. A large proportion of patients lost to follow-up may reduce the statistical power, although statistical and demographic data were comparable between follow-up and loss populations (Table S4). This study lacks cognitive data and follow-up imaging data; these limitations should be addressed in future research. Besides, scanners from different vendors, field strengths, parameters (e.g., voxel size, slice thickness), high sensitivity to magnetic field variations may affect results. Thus, cross-validation studies at different centers via different acquisition protocols and larger cohorts are required to confirm and improve the diagnostic potency and robustness of this evaluation methodology. In conclusion, MBS as quantified by MBHR (≤ 54.6%) on 7T SWI shows strong potential for detecting UMN involvement in ALS, correlating significantly with disease severity and progression. Future multi-center, longitudinal investigations are necessary to validate these findings, refine optimal MBHR thresholds, and elucidate the longitudinal trajectory of MBS throughout disease evolution. Abbreviations ALS Amyotrophic lateral sclerosis ALSFRS-R Revised amyotrophic Lateral sclerosis functional rating scale AUC Area under the curve CSF Cerebrospinal fluid fMRI Functional magnetic resonance imaging HCs Healthy controls HSP Hereditary spastic paraplegia LMN Lower motor neuron M1 Primary motor cortex MBHR Motor band hypointensity ratio MBS Motor band sign MGH UMNSs MGH upper motor neuron scales MRI Magnetic resonance imaging Oreo Dark-bright-dark ROC Receiver operating characteristic ROI Region of interest SWI Susceptibility-weighted imaging UMN Upper motor neuron ΔFS Disease progression rate Declarations Acknowledgements We extend our gratitude to all the patients who participated in this study; we also commemorate the nurses from the Department of Neurology and the electromyography and magnetic resonance imaging technicians at Beijing Tiantan Hospital. Author contributions H. P., J.J., Y.W., Z.Z., Y.W., X.H., Z.Z. contributed to conception and design of the study. X.H., Z.Z., L.C., S.Y., X.L., J.B., W.Z., N.W., N.C., L.Y., L.H. contributed to acquisition and analysis of the data. H.P., J.J., X.H. contributed to drafting the text or preparing the figures. Funding Not applicable. Availability of Data and materials These data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University(approval no. KY2023-013-02). All participants provided the informed consent under the principles of the Declaration of Helsinki before undergoing the scans and assessments. Consent for publication All patients in this paper consent for publication. Competing interests The authors declare that they have no competing interests. Author details 1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. 2 China National Clinical Research Center for Neurological Diseases, Beijing 100070, China. 3 Tiantan Neuroimaging Center of Excellence, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. 4 School of Biomedical Engineering, Capital Medical University, Beijing 100069, China. 5 Siemens Healthineers, MR Research Collaboration Team, Beijing 100102, China. References Kiernan MC, Vucic S, Cheah BC, et al. Amyotroph lateral Scler Lancet. 2011;377(9769):942–55. Cosottini M, Donatelli G, Costagli M, et al. High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis. AJNR Am J Neuroradiol. 2016;37(3):455–61. Budhu J, Rosenthal J, Williams E, Milligan Teaching T. NeuroImages: The Motor Band Sign in Amyotrophic Lateral Sclerosis. Neurology. 2021;96(7):e1092–3. Chung HS, Melkus G, Bourque P, Chakraborty Motor S. Band Sign in Motor Neuron Disease: A Marker for Upper Motor Neuron Involvement. Can J Neurol Sci. 2023;50(3):373–9. Endo H, Sekiguchi K, Shimada H, et al. Low signal intensity in motor cortex on susceptibility-weighted MR imaging is correlated with clinical signs of amyotrophic lateral sclerosis: a pilot study. J Neurol. 2018;265(3):552–61. Kwan JY, Jeong SY, Van Gelderen P, et al. Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology. PLoS ONE. 2012;7(4):e35241. Huber L, Handwerker DA, Jangraw DC et al. High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of Cortical Input and Output in Human M1. Neuron. 2017;96(6):1253–1263.e7. Northall A, Doehler J, Weber M et al. Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis. Brain Oct 10:awad351. 2023;10. Supplementary Files Additionalfile1R1annotated.docx Additional file 1: Table S1 Demographic data and clinical data of ALS, ALS mimics and HCs. Table S2 Demographic and clinical data between ALS subgroups whose MBHR ≤ 54.6%. Table S3 The comparison of MGH UMNSs and ALSFRS-R1 between ALS subgroups. Table S4 The comparison of demographic and clinical data between patients who completed follow-up and those excluded. Fig. S1 Flow chart of this study. Fig. S2 Comparison of MBHR among ALS, ALS mimics, and HCs. Fig. S3 Correlation analysis between MBHR and age in healthy controls. Fig. S4 Correlation analyses between MBHR and MGH UMNSs in ALS patients. Fig. S5 Correlation analysis between MBHR and ΔFS in ALS patients, 2 outlier patients with rapid progression were excluded.[6] Fig. S6 7T and 3T SWI images of 4 ALS patients. Fig. S7 7T and 3T SWI images of 4 other ALS patients. Fig. S8 Motor band sign in 7T SWI (1). Fig. S9 Motor band sign in 7T SWI (2). Fig. S10 Motor band sign in 7T SWI (3). Additionalfile2R1annotated.docx Additional file 2: Details about clinical assessment, MRI parameters, the MBHR measurement protocol, statistical analysis, intergroup consistency, and additional results. Cite Share Download PDF Status: Published Journal Publication published 18 Jun, 2025 Read the published version in Translational Neurodegeneration → Version 1 posted Reviewers agreed at journal 22 Apr, 2025 Reviewers invited by journal 22 Apr, 2025 Editor assigned by journal 22 Apr, 2025 First submitted to journal 21 Apr, 2025 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. 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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-5726741","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":446208831,"identity":"09aa7462-7639-4078-bc30-f91481e1d4d8","order_by":0,"name":"Xunyan Huang","email":"","orcid":"","institution":"Beijing Tiantan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xunyan","middleName":"","lastName":"Huang","suffix":""},{"id":446208832,"identity":"f4cb2b65-7272-40b1-9340-0e07137d4ef8","order_by":1,"name":"Zhe Zhang","email":"","orcid":"","institution":"Beijing Tiantan 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14:56:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5726741/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5726741/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40035-025-00491-8","type":"published","date":"2025-06-18T15:57:14+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81523112,"identity":"0379ddd7-083b-4e94-9320-393966ff5bba","added_by":"auto","created_at":"2025-04-28 08:18:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5145430,"visible":true,"origin":"","legend":"\u003cp\u003ePanel (A) ROI selection, MBHR calculation formula, and enlarged MBS schematic in 7T SWI from an ALS patient (White Box a). \u0026nbsp;Panel (\u003cstrong\u003eB\u003c/strong\u003e) ROC analysis for differentiating ALS subgroups versus all controls. Panel (\u003cstrong\u003eC\u003c/strong\u003e) Positive rates of the MBS across ALS subgroups. Panel (\u003cstrong\u003eD-F\u003c/strong\u003e) Magnified M1 regions in 7T SWI of a healthy control, a HSP patient, and an ALS patient, respectively (white boxes indicate regions of interest). [3] Panel (\u003cstrong\u003eG-H\u003c/strong\u003e) ΔFS comparisons between study cohorts (ALS vs. ALS mimics: \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.0001; ALS with MBS vs. without MBS: \u003cem\u003ep \u003c/em\u003e= 0.015), 2 outlier ALS patients with rapid progression wereexcluded. Panel (\u003cstrong\u003eI-J\u003c/strong\u003e) Correlation analyses between MBHR and ΔFS in ALS patients (\u003cem\u003er\u003c/em\u003e = -0.51, \u003cem\u003ep\u003c/em\u003e = 0.0006) and ALS mimics (\u003cem\u003er\u003c/em\u003e = -0.33, \u003cem\u003ep\u003c/em\u003e = 0.30). Abbreviations: ROIs, regions of interest; SWI, susceptibility-weighted imaging; ALS, amyotrophic lateral sclerosis; ROC, receiver operating characteristic; MBS, motor band sign; M1, primary motor cortex; HSP, hereditary spastic paraplegia; ΔFS, disease progression rate; MBHR, motor band hypointensity ratio.\u003c/p\u003e","description":"","filename":"LETTERFig1.png","url":"https://assets-eu.researchsquare.com/files/rs-5726741/v1/088eb523c77d0401789f5ad6.png"},{"id":85231302,"identity":"9d48577b-285d-4f74-af82-01346a855c7a","added_by":"auto","created_at":"2025-06-23 16:05:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5446331,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5726741/v1/66fa1f59-82d1-4451-b131-0c297f8093a2.pdf"},{"id":81522364,"identity":"2581cd62-7dab-4515-bbde-194ca57a3743","added_by":"auto","created_at":"2025-04-28 08:10:28","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":4749923,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file 1\u003c/strong\u003e: \u003cstrong\u003eTable S1 \u003c/strong\u003eDemographic data and clinical data of ALS, ALS mimics and HCs.\u0026nbsp;\u003cstrong\u003eTable S2 \u003c/strong\u003eDemographic and clinical data between ALS subgroups whose MBHR ≤ 54.6%. \u0026nbsp;\u003cstrong\u003eTable S3 \u003c/strong\u003eThe comparison of MGH UMNSs and ALSFRS-R1 between ALS subgroups. \u003cstrong\u003eTable S4\u003c/strong\u003e The comparison of demographic and clinical data between patients who completed follow-up and those excluded. \u0026nbsp;\u003cstrong\u003eFig. S1\u003c/strong\u003e Flow chart of this study. \u003cstrong\u003eFig. S2\u003c/strong\u003e Comparison of MBHR among ALS, ALS mimics, and HCs.\u003cstrong\u003e Fig. S3 \u003c/strong\u003eCorrelation analysis between MBHR and age in healthy controls. \u0026nbsp;\u003cstrong\u003eFig. S4 \u003c/strong\u003eCorrelation analyses between MBHR and MGH UMNSs in ALS patients. \u0026nbsp;\u003cstrong\u003eFig. S5 \u003c/strong\u003eCorrelation analysis between MBHR and ΔFS in ALS patients, 2 outlier patients with rapid progression were excluded.[6] \u003cstrong\u003e\u0026nbsp;Fig. S6\u003c/strong\u003e 7T and 3T SWI images of 4 ALS patients.\u003cstrong\u003e Fig. S7 \u003c/strong\u003e7T and 3T SWI images of 4 other ALS patients. \u003cstrong\u003e\u0026nbsp;Fig. S8\u003c/strong\u003e Motor band sign in 7T SWI (1). \u003cstrong\u003eFig. S9 \u003c/strong\u003eMotor band sign in 7T SWI (2). \u003cstrong\u003eFig. S10 \u003c/strong\u003eMotor band sign in 7T SWI (3).\u003c/p\u003e","description":"","filename":"Additionalfile1R1annotated.docx","url":"https://assets-eu.researchsquare.com/files/rs-5726741/v1/08b70ca321b2b28fbb601ca4.docx"},{"id":81522361,"identity":"c0bccb2e-625d-4bbb-8dbb-ef07b1441f57","added_by":"auto","created_at":"2025-04-28 08:10:28","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":52492,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file 2:\u003c/strong\u003e Details about clinical assessment, MRI parameters, the MBHR measurement protocol, statistical analysis, intergroup consistency, and additional results.\u003c/p\u003e","description":"","filename":"Additionalfile2R1annotated.docx","url":"https://assets-eu.researchsquare.com/files/rs-5726741/v1/b38b9bcb003aad33bce8d863.docx"}],"financialInterests":"","formattedTitle":"Diagnostic Value of the Motor Band Sign in Amyotrophic Lateral Sclerosis: A 7T Magnetic Resonance Imaging Study","fulltext":[{"header":"Main text","content":"\u003cp\u003eTo evaluate the diagnostic efficacy of the MBS in identifying UMN impairment via 7T SWI, this study prospectively recruited an ALS cohort at Beijing Tiantan Hospital between October 2021 and March 2023 (Fig. \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). All participants underwent standardized physical examinations, electromyography, and 7T MRI within a week. Quantitative assessment of MBS was performed using the motor band hypointensity ratio (MBHR, Fig.\u0026nbsp;1A), with details provided in Additional file 2 (The MBHR measurement protocol).\u003c/p\u003e\n\u003cp\u003eThe ALS cohort comprised 20 clinically definite ALS, 15 clinically probable ALS, 11 clinically probable laboratory-supported ALS, and 7 clinically possible ALS. Age- and gender-matched controls (n\u0026thinsp;=\u0026thinsp;62) included 50 healthy controls (HCs) and 12 ALS mimic cases: 6 hereditary spastic paraplegia (HSP) patients and 6 LMN syndrome patients. Demographic and clinical characteristics are detailed in Table \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eThe results of group differences (Kruskal-Wallis H test, details in Additional file 2: Statistical analysis) revealed significant MBHR variations among ALS patients, ALS mimics, and HCs (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; Fig. \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003eA). Specifically, ALS patients exhibited lower MBHR compared to both ALS mimics (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and HCs (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Significant MBHR differences were also observed among ALS subgroups, ALS mimics, and HCs (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; Fig. \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003eB). Additionally, no correlation was observed between MBHR and age in the HC group (r = -0.08, p\u0026thinsp;=\u0026thinsp;0.60; Fig. S3). Notably, we verified a significant MBHR-UMN impairment association in ALS (Fig. S4), confirming the potential of MBS as a promising neuroimaging biomarker for ALS UMN impairment.\u003c/p\u003e\n\u003cp\u003eMoreover, receiver operating characteristic (ROC) analysis demonstrated the diagnostic performance of the MBS in differentiating clinically definite ALS patients from all controls (red line in Fig.\u0026nbsp;1B), where an MBHR cutoff of 54.6% yielded an area under the curve (AUC) of 0.930 (95% confidence interval [CI]: 0.828\u0026ndash;1.000), with 90.0% sensitivity and 100% specificity. Application of this threshold revealed differential MBS prevalence across ALS diagnostic subgroups: 90.0% in clinically definite ALS, 73.3% in clinically probable ALS, 54.5% in clinically probable laboratory-supported ALS, and 42.9% in clinically possible ALS (Fig.\u0026nbsp;1C). Additionally, demographic and clinical characteristics of ALS subgroups with MBHR\u0026thinsp;\u0026le;\u0026thinsp;54.6% and ROC analyses for other ALS subgroups are provided in Table \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e and Additional file 2 (Additional results), respectively.\u003c/p\u003e\n\u003cp\u003eClinically definite/probable ALS patients exhibited significantly higher MGH upper motor neuron scales (MGH UMNSs, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028) and lower revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) scores (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027) compared to clinically probable laboratory-supported/possible ALS patients (Table S3). These functional differences may underlie the observed reduction in MBS prevalence in the latter groups.\u003c/p\u003e\n\u003cp\u003eAdditionally, comparative analysis revealed significantly faster disease progression in ALS patients versus ALS mimics (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; Fig.\u0026nbsp;1G). Among ALS patients, those exhibiting the MBS demonstrated accelerated progression compared to MBS-negative cases (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015; Fig.\u0026nbsp;1H). Furthermore, a strong negative correlation between MBHR and \u0026Delta;FS was observed in ALS patients (\u003cem\u003er\u003c/em\u003e = -0.51, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0006; Fig.\u0026nbsp;1I), whereas no significant association was observed in ALS mimics (\u003cem\u003er\u003c/em\u003e = -0.33, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.30; Fig.\u0026nbsp;1J). After excluding two outlier ALS patients with rapid progression, the significant association remained (Fig. S5).\u003c/p\u003e\n\u003cp\u003eConventional approaches for the MBS evaluation face challenges: subjective variability in visual assessments and technical limitations of quantitative methods (more details in Additional file 2: The MBHR measurement protocol). To overcome these limitations, our study adopted the adjacent subcortical white matter region as the reference standard, with two primary goals: enhancing clinical practicality through simplified protocol implementation and mitigating artifacts caused by 7T magnetic field inhomogeneities. This optimized SWI protocol demonstrated high interobserver consistency (Additional file 2: Intergroup consistency).\u003c/p\u003e\n\u003cp\u003eSuch results revealed a progressive decline in diagnostic sensitivity across ALS subgroups, paralleling reductions in diagnostic accuracy. Clinically probable laboratory-supported/possible ALS patients demonstrated significantly higher ALSFRS-R scores compared to clinically definite/probable ALS patients, suggesting earlier disease stages. These subgroups also exhibited milder UMN impairment, further indicating the MBS as a biomarker correlating with advanced disease burden and UMN degeneration severity. Although MBS detection is lower in these patients, a positive MBS can greatly boost diagnostic confidence. Integrating MBS as an additional UMN marker may accelerate diagnosis in ambiguous cases. For early-stage patients testing MBS-negative, follow-up MRI scans during disease progression could improve detection.\u003c/p\u003e\n\u003cp\u003eIn a subset of eight ALS patients who have clinical 3T MRI data available, 7T SWI demonstrated superior MBS detection rates (7/8 vs. 4/8 with 3T SWI) and provided enhanced visualization of lesion internal architecture (Figs. S6-S7). The study revealed that some ALS patients demonstrated an explicit stratified pattern on 7T SWI. We observed three layers (white rhomboids) between the hyperintense superficial grey matter layers (yellow arrowheads) and the grey-white matter junction (white arrowheads) in M1 in healthy controls as well as ALS mimics (Fig.\u0026nbsp;1D-E). In ALS patients, the signal intensity of the superficial and the deep layers in these three layers decreased, resulting in an Oreo-fashioned (dark-bright-dark) layered MBS (Fig.\u0026nbsp;1F). Detailed MBS images from all ALS patients are provided in Figs. S8-S10.\u003c/p\u003e\n\u003cp\u003eRecent functional MRI (fMRI) studies have confirmed laminar-specific cortical activation patterns in humans [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e], coinciding with histological evidence of ferritin-rich microglia predominantly localized in the middle and deep layers of the M1 [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. Our findings suggest that the observed Oreo-fashioned layered MBS may reflect the cytoarchitecture organization of M1. However, Northall et al. reported predominant iron deposition in M1 layer VI (deepest cortical layer) in ALS patients [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. The lack of SWI data and heterogeneous grouping of MBS-positive/negative cohorts might explain this discrepancy. Therefore, future research integrating submillimeter ultra-high-field MRI, iron-sensitive imaging, and disease pathology is necessary to further understand the layer-specific pathological features of ALS.\u003c/p\u003e\n\u003cp\u003eThe identification of disease progression biomarkers is critical for managing and treating ALS. Our findings supported accelerated progress in ALS patients with MBS and a strong inverse correlation between MBHR and \u0026Delta;FS. Thus, we deduced that the MBS strongly correlated with the disease progression, warranting more consideration in clinical practice.\u003c/p\u003e\n\u003cp\u003eThere are several limitations in this study. The small sample size of ALS patients and disease controls limits the generalization of the above results. A large proportion of patients lost to follow-up may reduce the statistical power, although statistical and demographic data were comparable between follow-up and loss populations (Table S4). This study lacks cognitive data and follow-up imaging data; these limitations should be addressed in future research. Besides, scanners from different vendors, field strengths, parameters (e.g., voxel size, slice thickness), high sensitivity to magnetic field variations may affect results. Thus, cross-validation studies at different centers via different acquisition protocols and larger cohorts are required to confirm and improve the diagnostic potency and robustness of this evaluation methodology.\u003c/p\u003e\n\u003cp\u003eIn conclusion, MBS as quantified by MBHR (\u0026le;\u0026thinsp;54.6%) on 7T SWI shows strong potential for detecting UMN involvement in ALS, correlating significantly with disease severity and progression. Future multi-center, longitudinal investigations are necessary to validate these findings, refine optimal MBHR thresholds, and elucidate the longitudinal trajectory of MBS throughout disease evolution.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Amyotrophic lateral sclerosis\u003c/p\u003e\n\u003cp\u003eALSFRS-R \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Revised amyotrophic Lateral sclerosis functional rating scale\u003c/p\u003e\n\u003cp\u003eAUC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Area under the curve\u003c/p\u003e\n\u003cp\u003eCSF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cerebrospinal fluid\u003c/p\u003e\n\u003cp\u003efMRI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Functional magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eHCs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Healthy controls\u003c/p\u003e\n\u003cp\u003eHSP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hereditary spastic paraplegia\u003c/p\u003e\n\u003cp\u003eLMN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Lower motor neuron\u003c/p\u003e\n\u003cp\u003eM1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Primary motor cortex\u003c/p\u003e\n\u003cp\u003eMBHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Motor band hypointensity ratio\u003c/p\u003e\n\u003cp\u003eMBS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Motor band sign\u003c/p\u003e\n\u003cp\u003eMGH UMNSs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;MGH upper motor neuron scales\u003c/p\u003e\n\u003cp\u003eMRI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eOreo \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Dark-bright-dark\u003c/p\u003e\n\u003cp\u003eROC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Receiver operating characteristic\u003c/p\u003e\n\u003cp\u003eROI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Region of interest\u003c/p\u003e\n\u003cp\u003eSWI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Susceptibility-weighted imaging\u003c/p\u003e\n\u003cp\u003eUMN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Upper motor neuron\u003c/p\u003e\n\u003cp\u003eΔFS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Disease progression rate\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extend our gratitude to all the patients who participated in this study; we also commemorate the nurses from the Department of Neurology and the electromyography and magnetic resonance imaging technicians at Beijing Tiantan Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH. P., J.J., Y.W., Z.Z., Y.W., X.H., Z.Z. contributed to conception and design of the study. X.H., Z.Z., L.C., S.Y., X.L., J.B., W.Z., N.W., N.C., L.Y., L.H. contributed to acquisition and analysis of the data. H.P., J.J., X.H. contributed to drafting the text or preparing the figures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University(approval no. KY2023-013-02). All participants provided the informed consent under the principles of the Declaration of Helsinki before undergoing the scans and assessments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients in this paper consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. \u003csup\u003e2\u003c/sup\u003eChina National Clinical Research Center for Neurological Diseases, Beijing 100070, China. \u003csup\u003e3\u003c/sup\u003eTiantan Neuroimaging Center of Excellence, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. \u003csup\u003e4\u003c/sup\u003eSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, China. \u003csup\u003e5\u003c/sup\u003eSiemens Healthineers, MR Research Collaboration Team, Beijing 100102, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKiernan MC, Vucic S, Cheah BC, et al. Amyotroph lateral Scler Lancet. 2011;377(9769):942\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosottini M, Donatelli G, Costagli M, et al. High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis. AJNR Am J Neuroradiol. 2016;37(3):455\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBudhu J, Rosenthal J, Williams E, Milligan Teaching T. NeuroImages: The Motor Band Sign in Amyotrophic Lateral Sclerosis. Neurology. 2021;96(7):e1092\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChung HS, Melkus G, Bourque P, Chakraborty Motor S. Band Sign in Motor Neuron Disease: A Marker for Upper Motor Neuron Involvement. Can J Neurol Sci. 2023;50(3):373\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEndo H, Sekiguchi K, Shimada H, et al. Low signal intensity in motor cortex on susceptibility-weighted MR imaging is correlated with clinical signs of amyotrophic lateral sclerosis: a pilot study. J Neurol. 2018;265(3):552\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwan JY, Jeong SY, Van Gelderen P, et al. Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology. PLoS ONE. 2012;7(4):e35241.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuber L, Handwerker DA, Jangraw DC et al. High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of Cortical Input and Output in Human M1. Neuron. 2017;96(6):1253\u0026ndash;1263.e7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNorthall A, Doehler J, Weber M et al. Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis. Brain Oct 10:awad351. 2023;10.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"translational-neurodegeneration","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tneu","sideBox":"Learn more about [Translational Neurodegeneration](http://translationalneurodegeneration.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/tneu/default.aspx","title":"Translational Neurodegeneration","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5726741/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5726741/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons, with a median survival of 3\u0026ndash;5 years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The key challenge in diagnosis lies in the early detection of upper motor neuron (UMN) impairment, which mainly depends on clinical examination but can be obscured by severe lower motor neuron (LMN) impairment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Consequently, searching for alternative UMN impairment markers has become a critical focus of ALS research.\u003c/p\u003e \u003cp\u003eRecent magnetic resonance imaging (MRI) studies indicated a band-shaped low signal intensity along the primary motor cortex (M1), termed the motor band sign (MBS) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. MBS has emerged as an imaging marker for identifying UMN impairment in ALS [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Researchers believe this hypointensity results from ferritin accumulation within activated microglia in M1 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. SWI has demonstrated increased sensitivity in detecting subtle, uniformly distributed iron deposits, becoming the current mainstream modality for identifying MBS. However, there is currently a lack of reports of MBS in 7T SWI.\u003c/p\u003e","manuscriptTitle":"Diagnostic Value of the Motor Band Sign in Amyotrophic Lateral Sclerosis: A 7T Magnetic Resonance Imaging Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 08:10:23","doi":"10.21203/rs.3.rs-5726741/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-04-22T10:31:06+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-22T08:52:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-22T06:32:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Translational Neurodegeneration","date":"2025-04-21T05:15:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"translational-neurodegeneration","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tneu","sideBox":"Learn more about [Translational Neurodegeneration](http://translationalneurodegeneration.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/tneu/default.aspx","title":"Translational Neurodegeneration","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b24a19cc-46d0-42ef-bd4e-99c5745f06ad","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-23T15:59:31+00:00","versionOfRecord":{"articleIdentity":"rs-5726741","link":"https://doi.org/10.1186/s40035-025-00491-8","journal":{"identity":"translational-neurodegeneration","isVorOnly":false,"title":"Translational Neurodegeneration"},"publishedOn":"2025-06-18 15:57:14","publishedOnDateReadable":"June 18th, 2025"},"versionCreatedAt":"2025-04-28 08:10:23","video":"","vorDoi":"10.1186/s40035-025-00491-8","vorDoiUrl":"https://doi.org/10.1186/s40035-025-00491-8","workflowStages":[]},"version":"v1","identity":"rs-5726741","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5726741","identity":"rs-5726741","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}