The alterations in brain network functional gradients and dynamic functional connectivity in Alzheimer's disease: a resting-state fMRI study.
Background and purpose: Alzheimer's disease (AD), the most common form of dementia worldwide, is characterized by progressive cognitive decline. Extensive evidence from dynamic functional connectivity (dFC) studies has demonstrated unstable functional states, reduced network flexibility, and impaire...
| Publicado en: | Frontiers in Aging Neuroscience pp. 1 - 17 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Frontiers Media S.A.
2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191005808&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191005808 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16634365 BG2U jtl: Frontiers in Aging Neuroscience issn: 16634365 maglogo: N pubinfo: dt: 2026 pid: 40038 pub: Frontiers Media S.A. artinfo: ui: 191005808 191005808 191005808 10.3389/fnagi.2025.1716076 191005808 ppf: 1 ppct: 16 formats: tig: atl: The alterations in brain network functional gradients and dynamic functional connectivity in Alzheimer's disease: a resting-state fMRI study. aug: au: Liu, Benqin Chen, Chunbing Cai, Pan Zhang, Jiaren Yang, Li Chen, Xu Ma, Xuejin Jiang, Xuetao Zhang, Anjie Song, Linfeng Jiang, Lin affil: Department of Radiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, China sug: subj: Alzheimer's Disease Brain Physiology Large-Scale Brain Networks Functional Connectivity Brain Mapping Cognition Disorders Machine Learning Human Magnetic Resonance Imaging Diagnosis, Brain Methods T-Tests Biological Markers Sensitivity and Specificity Funding Source Male Female Aged Middle Age Scales Pearson's Correlation Coefficient Fisher's Exact Test ROC Curve Aged: 65+ years Middle Aged: 45-64 years Male Female ab: Background and purpose: Alzheimer's disease (AD), the most common form of dementia worldwide, is characterized by progressive cognitive decline. Extensive evidence from dynamic functional connectivity (dFC) studies has demonstrated unstable functional states, reduced network flexibility, and impaired transitions between large-scale neurocognitive networks across the AD continuum. However, how these temporal abnormalities are embedded within the hierarchical spatial organization of brain networks, as captured by functional gradients (FG), and whether combined FG-dFC metrics can provide mechanistically interpretable and potentially sensitive imaging biomarkers, remain to be elucidated. Methods: This study enrolled 46 AD patients who were diagnosed according to the Amyloid/Tau/Neurodegeneration (ATN) biological diagnostic framework and 37 age- and sex-matched healthy controls (HC). All participants underwent resting-state fMRI. Functional gradients were derived using connectivity similarity matrices and diffusion embedding (aligned and standardized), while dFC was estimated with a sliding window approach and clustered into four recurrent states. Group differences were assessed with two-sample t -tests with Gaussian Random Field (GRF) correction. Correlation analyses included ATN biomarkers and cognitive scores. A linear support vector machine (SVM) with leave-one-out cross-validation evaluated classification performance based on significant FG features. Results: Compared to the healthy controls, AD patients exhibited widespread FG alterations between regions of the Default Mode Network (DMN) and the Sensorimotor Network (SMN). In the first gradient DMN, the left precuneus showed reduced gradient scores, whereas the right medial superior frontal gyrus and bilateral angular gyri were increased. In the first gradient of the SMN, the right supplementary motor area increased while bilateral superior temporal gyri decreased. Second-gradient reductions were confined to two regions: the left postcentral gyrus (SMN) and left middle occipital gyrus (visual network, VIS). The right medial superior frontal gyrus first-gradient score correlated negatively with T-Tau (r = −0.50, P = 0.006) and age (r = −0.36, P = 0.02); the right angular gyrus correlated negatively with age (r = −0.29, P = 0.04); the left precuneus correlated positively with age (r = 0.38, P = 0.009). dFC revealed four recurrent states (27.59, 17.67, 28.27, 26.47% of total occurrences). Relative to HC, AD showed higher FT and MDT in states 1–2 and lower scores in state 3, with NT unchanged, alongside state-dependent bidirectional connectivity changes (fronto-insular-sensorimotor increases; DMN-temporal and visuo-auditory decreases). The SVM achieved an AUC of 0.776, sensitivity 78.26%, specificity 67.57%, and accuracy 73.49%, with the right superior temporal gyrus within SMN first-gradient contributing most. Conclusion: AD is characterized by macro-scale hierarchical disorganization centered on the principal functional gradient, accompanied by reduced cross-state flexibility and state-dependent connectivity abnormalities. The combined functional gradient-dynamic functional connectivity (FG-dFC) analysis provides complementary spatiotemporal insights and reveals imaging features associated with T-Tau levels and age, offering new perspectives on the neuropathological mechanisms of AD and potential imaging biomarkers. Moreover, these network topology and dynamic connectivity metrics may prove useful for monitoring disease progression, evaluating treatment effects, and stratifying patients in future clinical and interventional studies. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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