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• Clinical Article •
Consistent brain function abnormalities in multiple sclerosis: A meta-analysis study
LIAO Juan  WANG Lu  LIU Ruishan  LI Hongwei  ZHUO Lihua 

DOI:10.12015/issn.1674-8034.2026.02.003.


[Abstract] Objective In recent years, resting-state functional magnetic resonance imaging (rs-fMRI) has become a key non-invasive tool for exploring brain functional abnormalities in multiple sclerosis (MS). However, findings across studies remain inconsistent. To address this, a systematic integration of existing rs-fMRI evidence is warranted to identify consistent patterns of functional brain alterations in MS patients.Materials and Methods Up to April 2025, a comprehensive literature search was performed in PubMed, Web of Science, Embase, Wanfang, and CNKI Database to screen for relevant studies that employed amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), or regional homogeneity (ReHo) to investigate spontaneous brain functional activity in multiple sclerosis (MS). Data analysis was conducted using anisotropic effect size seed-based d mapping (AES-SDM) software.Results A total of 11 studies (12 datasets) were included, involving 292 MS patients and 278 healthy controls (HCs). Compared with HCs, MS patients showed significantly increased spontaneous brain activity in right insula, Rolandic operculum, Heschl gyrus, supramarginal gyrus, bilateral thalamus, and left inferior frontal gyrus (orbital part), whereas significantly decreased activity was observed in the right lingual gyrus, cuneus cortex, calcarine/surrounding cortex, middle temporal gyrus, and striatum (caudate nucleus).Conclusions This study reveals consistent brain function changes in MS patients, involving related brain regions such as emotion regulation, cognition, sensation, vision and motor control. These findings not only deepen the understanding of the neuropathological mechanism of MS, but also provide potential biomarkers for disease diagnosis, progression monitoring and treatment effect evaluation.
[Keywords] multiple sclerosis；resting-state functional magnetic resonance imaging；magnetic resonance imaging；amplitude of low-frequency fluctuation；fractional amplitude of low-frequency fluctuation；regional homogeneity；meta-analysis

LIAO Juan1, 2   WANG Lu1, 2   LIU Ruishan1   LI Hongwei1   ZHUO Lihua1*  

1 Department of Radiology, the Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang 621000, China

2 Medical Imaging College, North Sichuan Medical College, Nanchong 637000, China

Corresponding author: ZHUO L H, E-mail: 1029511104@qq.com

Conflicts of interest   None.

Received  2025-09-18
Accepted  2026-01-06
DOI: 10.12015/issn.1674-8034.2026.02.003
DOI:10.12015/issn.1674-8034.2026.02.003.

[1]
HAKI M, AL-BIATI H A, AL-TAMEEMI Z S, et al. Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment[J/OL]. Medicine, 2024, 103(8): 37297 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/38394496/. DOI: 10.1097/MD.0000000000037297.
[2]
GIANNOPAPAS V, KITSOS D, TSOGKA A, et al. Sexual dysfunction therapeutic approaches in patients with multiple sclerosis: a systematic review[J]. Neurol Sci, 2023, 44(3): 873-880. DOI: 10.1007/s10072-022-06572-0.
[3]
WANG J, YANG L L. Blurred vision and limb weakness: be alert to multiple sclerosis[J]. Family Medicine, 2024, 12(24): 48-49.
[4]
CONTI L, PREZIOSA P, MEANI A, et al. Unraveling the substrates of cognitive impairment in multiple sclerosis: A multiparametric structural and functional magnetic resonance imaging study[J]. Eur J Neurol, 2021, 28(11): 3749-3759. DOI: 10.1111/ene.15023.
[5]
FILIPPI M, PREZIOSA P, ARNOLD D L, et al. Present and future of the diagnostic work-up of multiple sclerosis: the imaging perspective[J]. J Neurol, 2023, 270(3): 1286-1299. DOI: 10.1007/s00415-022-11488-y.
[6]
MAHMOUDI F, MCCARTHY M, NELSON F. Functional MRI and cognition in multiple sclerosis-Where are we now?[J/OL]. J Neuroimaging, 2025, 35(1): 13252 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/39636088/. DOI: 10.1111/jon.13252.
[7]
BOERWINKLE V L, NOWLEN M A, VAZQUEZ J E, et al. Resting-state fMRI seizure onset localization meta-analysis: comparing rs-fMRI to other modalities including surgical outcomes[J/OL]. Front Neuroimaging, 2024, 3: 1481858 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/39742390/. DOI: 10.3389/fnimg.2024.1481858.
[8]
ZHENG H, ZHAI T, LIN X, et al. The resting-state brain activity signatures for addictive disorders[J/OL]. Med (New York, NY), 2024, 5(3): 201-23.e6 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/38359839/. DOI: 10.1016/j.medj.2024.01.008.
[9]
WEN J J, GAO Y Y, LI M T, et al. Regional abnormalities of spontaneous brain activity in migraine: A coordinate-based meta-analysis[J]. J Neurosci Res, 2023, 101(8): 1205-1223. DOI: 10.1002/jnr.25191.
[10]
CHEN Z H, XU Q, YANG G, et al. Changes of fALFF in migraine patients caused by anxiety and depression: a cross-sectional fMRI study[J]. J Air Force Med Univ, 2023, 44(2): 105-110. DOI: 10.13276/j.issn.2097-1656.2023.02.002.
[11]
SHEN W, WANG X, LI Q, et al. Research on adults with subthreshold depression after aerobic exercise: a resting-state fMRI study based on regional homogeneity (ReHo)[J/OL]. Front Neurosci, 2024, 18: 1231883 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/38533447/. DOI: 10.3389/fnins.2024.1231883.
[12]
ZHOU E, WANG W, MA S, et al. Prediction of anxious depression using multimodal neuroimaging and machine learning[J/OL]. NeuroImage, 2024, 285: 120499 [2025-09-18]. https://doi.org/10.1016/j.neuroimage.2023.120499. DOI: 10.1016/j.neuroimage.2023.120499.
[13]
LIU H, CHEN H, WU B, et al. Functional cortical changes in relapsing-remitting multiple sclerosis at amplitude configuration: a resting-state fMRI study[J]. Neuropsychiatr Dis Treat, 2016, 12: 3031-3039. DOI: 10.2147/ndt.S120909.
[14]
LIU Y, MENG B, ZENG C, et al. Abnormal Baseline Brain Activity in Patients With Multiple Sclerosis With Simple Spinal Cord Involvement Detected by Resting-State Functional Magnetic Resonance Imaging[J]. J Comput Assist Tomogr, 2015, 39(6): 866-875. DOI: 10.1097/rct.0000000000000299.
[15]
PLATA-BELLO J, PÉREZ-MARTÍN Y, CASTAÑÓN-PÉREZ A, et al. The relationship between amplitude of low frequency fluctuations and gray matter volume of the mirror neuron system: Differences between low disability multiple sclerosis patients and healthy controls[J]. IBRO Rep, 2018, 5: 60-66. DOI: 10.1016/j.ibror.2018.09.002.
[16]
XU G, CHENG S, QU Y, et al. The functional alterations in primary migraine: A systematic review and meta-analysis protocol[J/OL]. Medicine, 2020, 99(10): e19019 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/32150049/. DOI: 10.1097/MD.0000000000019.
[17]
GRAY J P, MÜLLER V I, EICKHOFF S B, et al. Multimodal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies[J]. Am J Psychiatry, 2020, 177(5): 422-434. DOI: 10.1176/appi.ajp.2019.19050560.
[18]
PAGE M J, MCKENZIE J E, BOSSUYT P M, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews[J/OL]. BMJ, 2021, 372: n71 [2025-09-18]. https://doi.org/10.1136/bmj.n71. DOI: 10.1136/bmj.n71.
[19]
LAN H, SUO X, LI W, et al. Abnormalities of intrinsic brain activity in essential tremor: A meta-analysis of resting-state functional imaging[J]. Hum Brain Mapp, 2021, 42(10): 3156-3167. DOI: 10.1002/hbm.25425.
[20]
NIU X, GAO X, ZHANG M, et al. Meta-analysis of structural and functional brain alterations in internet gaming disorder[J/OL]. Front Psychiatry, 2022, 13: 1029344 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/37033880/. DOI: 10.3389/fpsyt.2022.1029344.
[21]
DU J, LIU Y, ZHU W. The altered functional status in vestibular migraine: A meta-analysis[J/OL]. Brain Behav, 2024, 14(6): e3591 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/38849984/. DOI: 10.1002/BRB3.3591.
[22]
WU G, LUO Y, GUO D, et al. A meta-analysis of resting-state fMRI in postherpetic neuralgia using AES-SDM[J/OL]. Front Neurosci, 2025, 19: 1556639 [2025-05-21]. https://pubmed.ncbi.nlm.nih.gov/40236945/. DOI: 10.3389/fnins.2025.1556639.
[23]
HU S, HAO Z, LI M, et al. Resting-state abnormalities in functional connectivity of the default mode network in migraine: A meta-analysis[J/OL]. Front Neurosci, 2023, 17: 1136790 [2025-05-21]. https://pubmed.ncbi.nlm.nih.gov/36937687/. DOI: 10.3389/fnins.2023.1136790.
[24]
DAI P, YU Y, SUN Q, et al. Abnormal changes of brain function and structure in patients with T2DM-related cognitive impairment: a neuroimaging meta-analysis and an independent validation[J/OL]. Nutr Diabetes, 2024, 14(1): 91 [2025-09-18]. https://doi.org/10.1038/S41387-024-00348-5. DOI: 10.1038/S41387-024-00348-5.
[25]
WANG L, LIU R S, LIAO J, et al. Changes of cerebral gray matter structure in patients with early-onset schizophrenia: a voxel-based morphometry meta-analysis[J]. Chin J Magn Reson Imaging, 2024, 15(11): 17-23. DOI: 10.12015/issn.1674-8034.2024.11.004.
[26]
LAI P, CHEN X, LIU J, et al. Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies[J/OL]. Brain Res Bull, 2025, 224: 111294 [2025-05-21]. https://pubmed.ncbi.nlm.nih.gov/40081505/. DOI: 10.1016/J.Brainresbull.2025.111294.
[27]
ZOU W, OU J, WU F, et al. Association of mild chronic obstructive pulmonary disease with all-cause mortality: A systematic review and meta-analysis[J/OL]. Pulmonology, 2025, 31(1): 2416813 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/38093693/. DOI: 10.1016/J.Pulmoe.2023.09.002.
[28]
ZHANG S, LIN J, CHENG Y, et al. Aberrant resting-state brain activity in Huntington's disease: A voxel-based meta-analysis[J/OL]. Front Neurol, 2023, 14: 1124158 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/37064205/. DOI: 10.3389/fneur.2023.1124158.
[29]
MA X H, YANG M Y, WU X, et al. Meta-analysis of handedness distribution in patients with schizophrenia and autism[J]. Chinese Journal of Anatomy, 2025, 48(1): 53-59. DOI: 10.3969/j.issn.1001-1633.2025.01.010.
[30]
RADUA J, FORTEA L, GOIKOLEA J M, et al. Meta-analysis of the effects of adjuvant drugs in co-occurring bipolar and substance use disorder[J]. Span J Psychiatry Ment Health, 2024, 17(4): 239-250. DOI: 10.1016/j.rpsm.2023.01.005.
[31]
DOBRYAKOVA E, HAFIZ R, IOSIPCHUK O, et al. ALFF response interaction with learning during feedback in individuals with multiple sclerosis[J/OL]. Mult Scler Relat Disord, 2023, 70: 104510 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/36706463/. DOI: 10.1016/J.MSARD.2023.104510.
[32]
DU X F, LIU J, HUA Q F, et al. Relapsing-Remitting Multiple Sclerosis Is Associated With Regional Brain Activity Deficits in Motor- and Cognitive-Related Brain Areas[J/OL]. Front Neurol, 2019, 10: 1136 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/31849801/. DOI: 10.3389/fneur.2019.01136.
[33]
LIU Y, DUAN Y, LIANG P, et al. Baseline brain activity changes in patients with clinically isolated syndrome revealed by resting-state functional MRI[J]. Acta Radiol, 2012, 53(9): 1073-1078. DOI: 10.1258/AR.2012.120269.
[34]
LIU Y, LIANG P, DUAN Y, et al. Brain plasticity in relapsing-remitting multiple sclerosis: evidence from resting-state fMRI[J]. J Neurol Sci, 2011, 304(1-2): 127-131. DOI: 10.1016/J.Jns.2011.01.023.
[35]
RIAZI A H, RABBANI H, KAFIEH R. Dynamic Brain Connectivity in Resting-State FMRI Using Spectral ICA and Graph Approach: Application to Healthy Controls and Multiple Sclerosis[J/OL]. Diagnostics (Basel), 2022, 12(9): 2263 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/36140663/. DOI: 10.3390/diagnostics12092263.
[36]
WU L, ZHANG Y, ZHOU F, et al. Altered intra-and interregional synchronization in relapsing-remitting multiple sclerosis: A resting-state fMRI study[J]. Neuropsychiatr Dis Treat, 2016, 12: 853-862. DOI: 10.2147/NDT.S98962.
[37]
YIN P, LIU Y, XIONG H, et al. Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement[J/OL]. Br J Radiol, 2018, 91(1083): 20150777 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/29227148/. DOI: 10.1259/BJR.20150777.
[38]
ZHOU F, ZHUANG Y, WU L, et al. Increased thalamic intrinsic oscillation amplitude in relapsing-remitting multiple sclerosis associated with the slowed cognitive processing[J]. Clin Imaging, 2014, 38(5): 605-610. DOI: 10.1016/J.Clinimag.2014.05.006.
[39]
LIU X L, XU L, WU A X, et al. Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica[J]. Acta Anat Sin, 2024, 55(1): 17-24. DOI: 10.16098/j.issn.0529-1356.2024.01.003.
[40]
YOUNG C A, ROG D J, TANASESCU R, et al. Multiple Sclerosis vision questionnaire (MSVQ-7): Reliability, validity, precision and discrimination[J/OL]. Mult Scler Relat Disord, 2023, 80: 105115 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/37931488/. DOI: 10.1016/J.MSARD.2023.105115.
[41]
GALLO A, BISECCO A, BONAVITA S, et al. Functional plasticity of the visual system in multiple sclerosis[J/OL]. Front Neurol, 2015, 6: 79 [2025-05-25]. https://pubmed.ncbi.nlm.nih.gov/25904894/. DOI: 10.3389/fneur.2015.00079.
[42]
JENKINS T M, TOOSY A T, CICCARELLI O, et al. Neuroplasticity predicts outcome of optic neuritis independent of tissue damage[J]. Ann Neurol, 2010, 67(1): 99-113. DOI: 10.1002/ana.21823.
[43]
ZHU Y Y, WANG Y, HE T, et al. Study on coherent regional homogeneity of the whole brain in acute and remissive multiple sclerosis[J]. Chin J Magn Reson Imaging, 2022, 13(3): 31-36. DOI: 10.12015/issn.1674-8034.2022.03.007.
[44]
STRIK M, EIJLERS A J, DEKKER I, et al. Sensorimotor network dynamics predict decline in upper and lower limb function in people with multiple sclerosis[J]. Mult Scler, 2023, 29(1): 81-91. DOI: 10.1177/13524585221125372.
[45]
CAO Y, DIAO W, TIAN F, et al. Gray Matter Atrophy in the Cortico-Striatal-Thalamic Network and Sensorimotor Network in Relapsing-Remitting and Primary Progressive Multiple Sclerosis[J]. Neuropsychol Rev, 2021, 31(4): 703-720. DOI: 10.1007/S11065-021-09479-3.
[46]
PETRIDES M. On the evolution of polysensory superior temporal sulcus and middle temporal gyrus: A key component of the semantic system in the human brain[J]. J Comp Neurol, 2023, 531(18): 1987-1995. DOI: 10.1002/cne.25521.
[47]
CHEN S, XUE B, ZHOU R, et al. Abnormal stability of dynamic functional architecture in drug-naïve children with attention-deficit/hyperactivity disorder[J/OL]. BMC psychiatry, 2024, 24(1): 851 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/39592983/. DOI: 10.1186/S12888-024-06310-0.
[48]
ISHIDA H, GRANDI L C, FORNIA L. Secondary somatosensory and posterior insular cortices: a somatomotor hub for object prehension and manipulation movements[J/OL]. Front Integr Neurosci, 2024, 18: 1346968 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/38725800/. DOI: 10.3389/fnint.2024.1346968.
[49]
AMIN M, ONTANEDA D. Thalamic Injury and Cognition in Multiple Sclerosis[J/OL]. Front Neurol, 2020, 11: 623914 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/33613423/. DOI: 10.3389/fneur.2020.623914.
[50]
ZHANG Y N, HUANG Y R, LIU J L, et al. Aberrant resting-state cerebral blood flow and its connectivity in primary dysmenorrhea on arterial spin labeling MRI[J]. Magn Reson Imaging, 2020, 73: 84-90. DOI: 10.1016/J.MRI.2020.07.012.
[51]
TRIARHOU L C. Cytoarchitectonics of the Rolandic operculum: morphofunctional ponderings[J]. Brain Struct Funct, 2021, 226(4): 941-950. DOI: 10.1007/S00429-021-02258-Z.
[52]
XIE J, ZHANG W, BAI Y, et al. Neural mechanisms of tinnitus: An exploration from the perspective of varying severity levels[J/OL]. Brain Res Bull, 2025, 222: 111250 [2025-09-18]. https://doi.org/10.1016/J.Brainresbull.2025.111250. DOI: 10.1016/J.Brainresbull.2025.111250.
[53]
ZAMOSCIK V, SCHMIDT S N L, BRAVO R, et al. Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level[J/OL]. Sci Rep, 2021, 11(1): 21637 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/34737364/. DOI: 10.1038/S41598-021-01164-Y.
[54]
KHALIGHINEJAD B, PATEL P, HERRERO J L, et al. Functional characterization of human Heschl's gyrus in response to natural speech[J/OL]. NeuroImage, 2021, 235: 118003 [2025-09-18]. https://doi.org/10.1016/J.Neuroimage.2021.118003. DOI: 10.1016/J.Neuroimage.2021.118003.
[55]
LIANG X. Machine learning study on distinguishing multiple sclerosis and neuromyelitis optica spectrum disorders based on multi-level functional MRI features[D]. Nanchang Univ Med Coll, 2024.
[56]
CHEN Q, PENG Y, GAN Q X, et al. Research Progress on Imaging of Multiple Sclerosis[J]. International Journal of Neurology and Neurosurgery, 2023, 50(3): 91-96. DOI: 10.16636/j.cnki.jinn.1673-2642.2023.03.017.
[57]
ENGEL-YEGER B, DELUCA J, HAKE P, et al. The role of sensory processing difficulties, cognitive impairment, and disease severity in predicting functional behavior among patients with multiple sclerosis[J]. Disabil Rehabil, 2021, 43(8): 1129-1136. DOI: 10.1080/09638288.2019.1653998.
[58]
ZHOU Y, SONG Y, CHEN C, et al. Abnormal amplitude of low-frequency fluctuation values as a neuroimaging biomarker for major depressive disorder with suicidal attempts in adolescents: A resting-state fMRI and support vector machine analysis[J/OL]. Front Psychol, 2023, 14: 1146944 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/36910742/. DOI: 10.3389/fpsyg.2023.1146944.
[59]
ZHOU M, LI H, QU X, et al. Machine Learning-Based Identification of Children With Intermittent Exotropia Using Multiple Resting-State Functional Magnetic Resonance Imaging Features[J/OL]. Brain Behav, 2025, 15(5): e70556 [2025-09-18]. https://pubmed.ncbi.nlm.nih.gov/40356536/. DOI: 10.1002/BRB3.70556.

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