Skip to content
2000
Volume 22, Issue 11
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Introduction

The primary objective of this study was to examine changes in brain network architecture across multiple frequency bands using spectral analysis of both weighted and binarized functional connectivity networks. This cross-sectional observational study, conducted as a secondary analysis of a publicly available EEG dataset, analyzed spectral coherence measurements from 25 patients with Alzheimer’s disease (AD) and 25 age- and sex-matched healthy controls (HC). Nevertheless, the modest sample size and cultural homogeneity of the dataset may limit the statistical power and generalizability of the results. A data-driven thresholding approach was employed to generate binary networks, allowing a robust comparison of connectivity disruptions associated with AD.

Methods

Brain network features derived from the graph Laplacian, including weighted Fiedler value, spectral range, and Middle Eigenvalue, were analyzed across seven frequency layers: delta, theta, alpha1, alpha2, beta1, beta2, and gamma. For binary networks, the Fiedler value was calculated after thresholding. Statistical group comparisons between AD and HC were performed using t-tests ( 0.05), and each feature was assessed based on the number of frequency bands showing significant differences.

Results

Among all features, the weighted Fiedler value was the most discriminative, showing significant reductions in AD patients within the alpha2 and beta1 bands. In binary networks, the Fiedler value remained significantly lower in AD within the alpha2 band, confirming topological degradation even without edge weight information. Other spectral features showed similar trends, but did not reach statistical significance in the binary networks.

Discussion

The consistent decline in Fiedler value across both weighted and binary networks indicates a global reduction in connectivity characteristic of AD. These spectral markers offer a quantitative and interpretable framework for understanding the progressive disconnection syndrome in AD.

Conclusion

This study demonstrates significant alterations in Laplacian spectral features of brain networks between the AD and HC groups across specific frequency bands. These exploratory findings indicate that the spectral features, particularly the Fiedler value, consistently differentiate AD patients from healthy controls across frequency bands, suggesting its potential as a biomarker. However, larger and longitudinal studies are needed to confirm its diagnostic and prognostic utility. The combined use of weighted and binarized connectivity matrices enhances analytical sensitivity and facilitates the application of spectral graph theory for the early detection and monitoring of AD.

Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050434251251008104505
2025-10-24
2026-02-07
Loading full text...

Full text loading...

References

  1. DaiZ. LinQ. LiT. Disrupted structural and functional brain networks in Alzheimer’s disease.Neurobiol. Aging201975718210.1016/j.neurobiolaging.2018.11.005 30553155
    [Google Scholar]
  2. BrierM.R. ThomasJ.B. AncesB.M. Network dysfunction in Alzheimer’s disease: Refining the disconnection hypothesis.Brain Connect.20144529931110.1089/brain.2014.0236 24796856
    [Google Scholar]
  3. KarimS.M.S. FahadM.S. RathoreR.S. Identifying discriminative features of brain network for prediction of Alzheimer’s disease using graph theory and machine learning.Front. Neuroinform.202418138472010.3389/fninf.2024.1384720 38957548
    [Google Scholar]
  4. PalmqvistS. SchöllM. StrandbergO. Earliest accumulation of β-amyloid within the default-mode network and its association with brain connectivity.Nat. Commun.201781121210.1038/s41467‑017‑01150‑x
    [Google Scholar]
  5. JacobsenJ.S. Amyloid-β accumulation and connectivity disruptions in preclinical Alzheimer’s disease.Brain201714027392749
    [Google Scholar]
  6. RubinovM. SpornsO. Complex network measures of brain connectivity: Uses and interpretations.Neuroimage20105231059106910.1016/j.neuroimage.2009.10.003 19819337
    [Google Scholar]
  7. FornitoA. ZaleskyA. BullmoreE. Fundamentals of brain network analysis.Academic press2016
    [Google Scholar]
  8. KhazaeeA MohammadiA OreallyR Study of brain network in Alzheimers disease using wavelet-based graph theory method.arXiv2024arXiv-2409
    [Google Scholar]
  9. ZaleskyA. FornitoA. BullmoreE.T. Network-based statistic: Identifying differences in brain networks.Neuroimage20105341197120710.1016/j.neuroimage.2010.06.041 20600983
    [Google Scholar]
  10. RubidoN BatziouV FuadM VuksanovicV. The classification of Alzheimer’s disease and mild cognitive impairment improved by dynamic functional network analysis.arXiv2025arXiv25050345810.48550/arXiv.2505.03458
    [Google Scholar]
  11. HuC. ChengL. SepulcreJ. A spectral graph regression model for learning brain connectivity of Alzheimer’s disease.PLoS One2015105e012813610.1371/journal.pone.0128136 26024224
    [Google Scholar]
  12. de HaanW. van der FlierW.M. WangH. Van MieghemP.F.A. ScheltensP. StamC.J. Disruption of functional brain networks in Alzheimer’s disease: What can we learn from graph spectral analysis of resting-state magnetoencephalography?Brain Connect.201222455510.1089/brain.2011.0043 22480296
    [Google Scholar]
  13. DaianuM. MezherA. JahanshadN. Spectral graph theory and graph energy metrics show evidence for the Alzheimer’s disease disconnection syndrome in APOE-4 risk gene carriers.015 IEEE 12th International Symposium on Biomedical Imaging (ISBI). Brooklyn, NY, USA, 16-19 April 2015sd, pp. 458-46110.1109/ISBI.2015.7163910
    [Google Scholar]
  14. AlharbiH. JuanatasR.A. Al HejailiA. LimS. Spectral graph convolutional neural network for Alzheimer’s disease diagnosis and multi-disease categorization from functional brain changes in magnetic resonance images.Front. Neuroinform.202418149557110.3389/fninf.2024.1495571 39539804
    [Google Scholar]
  15. SharmaR. MeenaH.K. Graph based novel features for detection of Alzheimer’s disease using EEG signals.Biomed. Signal Process. Control202510310738010.1016/j.bspc.2024.107380
    [Google Scholar]
  16. ChungF.R. Spectral graph theory.American Mathematical Soc.199792207
    [Google Scholar]
  17. BanerjeeA. JostJ. van LingenE. Spectra of graph Laplacians: Spectral measures and their applications.Linear Algebra Appl.200942811-1230153026
    [Google Scholar]
  18. de LangeS.C. ScholtensL.H. de ReusM.A. van den HeuvelM.P. Rich club definition and analysis in brain networks: A review.Neurosci. Biobehav. Rev.2014473446
    [Google Scholar]
  19. DolciG SagliaS BrusiniL CalhounV D GalazzoI B MenegazG Algebraic connectivity enhances hyperedge specificity in the Alzheimer’s disease continuum.arXiv2025arXiv25080125210.1016/j.bspc.2024.107380
    [Google Scholar]
  20. ChengB. Incomplete multimodal Alzheimer’s disease classification via bidirectional GAN and spectral graph learning.In: Advanced Intelligent Computing Technology and Applications.SingaporeSpringer202545746810.48550/arXiv.2508.01252
    [Google Scholar]
  21. VermaP. NagarajanS. RajA. Spectral graph theory of brain oscillations—-Revisited and improved.Neuroimage202224911891910.1016/j.neuroimage.2022.118919 35051584
    [Google Scholar]
  22. SpornsO. Structure and function of complex brain networks.Dialogues Clin. Neurosci.201315324726210.31887/DCNS.2013.15.3/osporns 24174898
    [Google Scholar]
  23. SarwarT. RamamohanaraoK. ZaleskyA. ConnellyA. Mapping connectomes with diffusion MRI: Deterministic or probabilistic tractography?Magn. Reson. Med.20198121368138410.1002/mrm.27471 30303550
    [Google Scholar]
  24. CroftsJ.J. ForresterM. O’DeaR.D. TassP.A. BreakspearM. Network spectral dynamics of brain oscillations and cognitive decline in Alzheimer’s disease.Neuroimage2016133256270
    [Google Scholar]
  25. GuillonJ. AttalY. ColliotO. Loss of brain inter-frequency hubs in Alzheimer’s disease.Sci. Rep.2017711087910.1038/s41598‑017‑07846‑w 28883408
    [Google Scholar]
  26. WangJ. ZuoX. HeY. Graph-based network analysis of resting-state functional MRI.Front. Syst. Neurosci.201041610.3389/fnsys.2010.00016 20589099
    [Google Scholar]
  27. HodgsonK. PoldrackR.A. CurranJ.E. Shared genetic factors influence head motion during MRI and body mass index.Cereb. Cortex201727125539554610.1093/cercor/bhw321 27744290
    [Google Scholar]
  28. ZhaoQ. LuH. MetmerH. GuoQ. WangP. Altered functional brain networks and the APOE ε4 allele in Alzheimer’s disease: A systematic review.J. Alzheimers Dis.202179310131028
    [Google Scholar]
  29. ChenX.X. ZengM.X. CaiD. ZhouH.H. WangY.J. LiuZ. Correlation between APOE4 gene and gut microbiota in Alzheimer’s disease.Benef. Microbes202314434936010.1163/18762891‑20220116 38661357
    [Google Scholar]
  30. LiY. YaoZ. YuY. FuY. ZouY. HuB. The influence of cerebrospinal fluid abnormalities and ApoE 4 on PHF-tau protein: Evidence from voxel analysis and graph theory.Front. Aging Neurosci.20191120810.3389/fnagi.2019.00208 31440157
    [Google Scholar]
  31. CanuetL. Resting-state EEG source localization and functional connectivity in Alzheimer’s disease: An eLORETA study.Neuroimage2012613598611
    [Google Scholar]
  32. BabiloniC. Brain connectivity changes in Alzheimer’s disease: A review of EEG and MEG studies.Neurosci. Biobehav. Rev.202011893110
    [Google Scholar]
  33. RossiniP.M. EEG and MEG in the diagnosis and prognosis of Alzheimer’s disease.Clin. Neurophysiol.202013114871500
    [Google Scholar]
  34. AhmadAL Sanchez-BornotJ SoteroR C CoyleD IdrisZ FayeI. Towards improving Alzheimer’s intervention: A machine learning approach for biomarker detection through combining MEG and MRI pipelines.arXiv2024arXiv24080481510.48550/arXiv.2408.04815
    [Google Scholar]
  35. StamC.J. Modern network science of neurological disorders.Nat. Rev. Neurosci.2014151068369510.1038/nrn3801 25186238
    [Google Scholar]
  36. HoganM.J. Functional connectivity changes in Alzheimer’s disease revealed by MEG.Neurobiol. Aging202110595103
    [Google Scholar]
  37. CohenM.X. MEG biomarkers of Alzheimer’s disease progression.Alzheimers Res. Ther.202113113
    [Google Scholar]
  38. YangS. BornotJ.M.S. Wong-LinK. PrasadG. M/EEG-based bio-markers to predict the MCI and Alzheimer’s disease: A review from the ML perspective.IEEE Trans. Biomed. Eng.201966102924293510.1109/TBME.2019.2898871 30762522
    [Google Scholar]
  39. TeipelS.J. Resting-state EEG network alterations in prodromal Alzheimer’s disease.Neurobiol. Aging20175494103
    [Google Scholar]
  40. JedynakM. Graph spectral analysis of MEG data in Alzheimer’s disease.Front. Neurosci.202014110
    [Google Scholar]
  41. RajA. Graph-based network classification in Alzheimer’s disease using Laplacian spectra.Neuroimage2020219117026
    [Google Scholar]
  42. PiniL. Can misfolded proteins spread via brain connectivity?J. Alzheimers Dis.2025[Epub ahead of Print]
    [Google Scholar]
  43. BucknerR.L. SepulcreJ. TalukdarT. Cortical hubs revealed by intrinsic functional connectivity: Mapping, assessment of stability, and relation to Alzheimer’s disease.J. Neurosci.20092961860187310.1523/JNEUROSCI.5062‑08.2009 19211893
    [Google Scholar]
  44. FilippiniN. MacIntoshB.J. HoughM.G. Distinct patterns of brain activity in young carriers of the APOE -ε4 allele.Proc. Natl. Acad. Sci. USA2009106177209721410.1073/pnas.0811879106 19357304
    [Google Scholar]
  45. SepulcreJ. SabuncuM.R. BeckerA. SperlingR. JohnsonK.A. In vivo characterization of the early states of the amyloid-beta network.Brain201313672239225210.1093/brain/awt146 23801740
    [Google Scholar]
  46. JonesD.T. KnopmanD.S. GunterJ.L. Cascading network failure across the Alzheimer’s disease spectrum.Brain2016139254756210.1093/brain/awv338 26586695
    [Google Scholar]
  47. VogelJ.W. Vachon-PresseauE. PichetB.A. TamA. Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic familial Alzheimer’s disease.Alzheimers Dement.2018145671682
    [Google Scholar]
  48. FranzmeierN. HaakK.V. DüzelE. van EimerenT. Functional connectivity alterations as markers for early and late stages of Alzheimer’s disease spectrum.Nat. Rev. Neurol.2020169520533
    [Google Scholar]
  49. SperlingR.A. RentzD.M. JohnsonK.A. The A4 study: Stopping AD before symptoms begin?Sci. Transl. Med.20146228228fs1310.1126/scitranslmed.3007941 24648338
    [Google Scholar]
  50. FinnE.S. ShenX. ScheinostD. Functional connectome fingerprinting: Identifying individuals using patterns of brain connectivity.Nat. Neurosci.201518111664167110.1038/nn.4135 26457551
    [Google Scholar]
  51. ByrgeL. KennedyD.P. Identifying individual functional connectomes using the minimum distance method.Neuroimage2019186518527
    [Google Scholar]
  52. KashyapR. KongR. BhattacharjeeS. LiJ. Individual-specific functional connectivity fingerprints predict cognition and behavior.Hum. Brain Mapp.2019403805816
    [Google Scholar]
  53. De DomenicoM. SasaiS. ArenasA. Mapping multiplex hubs in human functional brain networks.Front. Neurosci.20161032610.3389/fnins.2016.00326 27471443
    [Google Scholar]
  54. BianconiG. Multilayer networks: Structure and function.Oxford university press201810.1093/oso/9780198753919.001.0001
    [Google Scholar]
  55. CaiL. WeiX. LiuJ. Functional integration and segregation in multiplex brain networks for Alzheimer’s disease.Front. Neurosci.2020145110.3389/fnins.2020.00051 32132892
    [Google Scholar]
  56. Canal-GarciaA. Gómez-RuizE. MijalkovM. ChangY.W. VolpeG. PereiraJ.B. Multiplex connectome changes across the alzheimer’s disease spectrum using gray matter and amyloid data.Cereb. Cortex202232163501351510.1093/cercor/bhab429 35059722
    [Google Scholar]
  57. EchegoyenI. López-SanzD. MaestúF. BuldúJ.M. From single layer to multilayer networks in mild cognitive impairment and Alzheimer’s disease.J Phys Complex20212404502010.1088/2632‑072X/ac3ddd
    [Google Scholar]
  58. PresignyC. Characterization of multilayer networks: Theory and applications to the brain.Doctoral Thesis2023
    [Google Scholar]
  59. ShouG. YuanH. DingL. Mapping brain networks using multimodal data. Handbook of Neuroengineering.Springer20232975302510.1007/978‑981‑16‑5540‑1_83
    [Google Scholar]
  60. YuM. EngelsM.M.A. HillebrandA. Selective impairment of hippocampus and posterior hub areas in Alzheimer’s disease: An MEG-based multiplex network study.Brain201714051466148510.1093/brain/awx050 28334883
    [Google Scholar]
  61. EngelsM.M.A. StamC.J. van der FlierW.M. ScheltensP. de WaalH. van StraatenE.C.W. Declining functional connectivity and changing hub locations in Alzheimer’s disease: An EEG study.BMC Neurol.201515114510.1186/s12883‑015‑0400‑7 26289045
    [Google Scholar]
  62. SorrentinoP. Complex networks and early diagnosis: Graph theoretical metrics and multiplex networks in Alzheimer’s disease.Entropy20212314
    [Google Scholar]
  63. VecchioF. MiragliaF. MarraC. Human brain networks in cognitive decline: A graph theoretical analysis of cortical connectivity from EEG data.J. Alzheimers Dis.201441111312710.3233/JAD‑132087 24577480
    [Google Scholar]
  64. BehrouziniaS. KhanteymooriA. Topological biomarkers of Alzheimer’s disease from functional brain network analysis.Curr. Alzheimer Res.20252210.2174/0115672050399190250815070642 40873287
    [Google Scholar]
  65. ChungF.R.K. Spectral graph theory.Providence, RIAmerican Mathematical Society1997Vol. 92
    [Google Scholar]
  66. BanerjeeA. JostJ. On the spectrum of the normalized graph Laplacian.Linear Algebra Appl.200842811-123015302210.1016/j.laa.2008.01.029
    [Google Scholar]
  67. DimitriadisS.I. ZacharopoulosG. Graph laplacian spectrum of structural brain networks is subject-specific, repeatable but highly dependent on graph construction scheme.bioRxiv202310.1101/2023.05.31.543029
    [Google Scholar]
  68. DaianuM. Algebraic connectivity of brain networks shows patterns of segregation leading to reduced network robustness in Alzheimer’s disease.MICCAI Workshop Boston, MA, USA, September 2014, pp. 55-6410.1007/978‑3‑319‑11182‑7_6
    [Google Scholar]
  69. LiH. YaoR. XiaX. YinG. DengH. YangP. Adjustment of synchronization stability of dynamic brain-networks based on feature fusion.Front. Hum. Neurosci.2019139810.3389/fnhum.2019.00098 31001095
    [Google Scholar]
  70. BenigniB. GhavasiehA. CorsoA. d’AndreaV. De DomenicoM. Persistence of information flow: A multiscale characterization of human brain.Netw. Neurosci.20215312010.1162/netn_a_00203 34746629
    [Google Scholar]
  71. ThantT. YagerJ. Updating apathy: Using research domain criteria to inform clinical assessment and diagnosis of disorders of motivation.J. Nerv. Ment. Dis.2019207970771410.1097/NMD.0000000000000860 30256334
    [Google Scholar]
/content/journals/car/10.2174/0115672050434251251008104505
Loading
/content/journals/car/10.2174/0115672050434251251008104505
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test