Decoupling of regional neural activity and inter-regional functional connectivity in Alzheimer’s disease: a simultaneous PET/MR study

Somayeh Maleki Balajoo, Farzaneh Rahmani, Reza Khosrowabadi, Chun Meng, Simon B. Eickhoff, Timo Grimmer, Mojtaba Zarei, Alexander Drzezga, Christian Sorg, Masoud Tahmasian*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Purpose: Alzheimer’s disease (AD) and mild cognitive impairment (MCI) are characterized by both aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). However, the effect of AD/MCI on the coupling between regional neural activity (measured by regional fluorodeoxyglucose imaging (rFDG)) and inter-regional FC (measured by resting-state functional magnetic resonance imaging (rs-fMRI)) is poorly understood. Methods: We scanned 19 patients with MCI, 33 patients with AD, and 26 healthy individuals by simultaneous FDG-PET/rs-fMRI and assessed rFDG and inter-regional FC metrics (i.e., clustering coefficient and degree centrality). Next, we examined the potential moderating effect of disease status (MCI or AD) on the link between rFDG and inter-regional FC metrics using hierarchical moderated multiple regression analysis. We also tested this effect by considering interaction between disease status and inter-regional FC metrics, as well as interaction between disease status and rFDG. Results: Our findings revealed that both rFDG and inter-regional FC metrics were disrupted in MCI and AD. Moreover, AD altered the relationship between rFDG and inter-regional FC metrics. In particular, we found that AD moderated the effect of inter-regional FC metrics of the caudate, parahippocampal gyrus, angular gyrus, supramarginal gyrus, frontal pole, inferior temporal gyrus, middle frontal, lateral occipital, supramarginal gyrus, precuneus, and thalamus on predicting their rFDG. On the other hand, AD moderated the effect of rFDG of the parietal operculum on predicting its inter-regional FC metric. Conclusion: Our findings demonstrated that AD decoupled the link between regional neural activity and functional segregation and global connectivity across particular brain regions.

Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume49
Issue number9
Pages (from-to)3173-3185
ISSN1619-7070
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Alzheimer’s disease
  • Functional connectivity
  • Graph analysis
  • Mild cognitive impairment
  • Neural activity
  • PET/MR
  • Brain/diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging/methods
  • Positron-Emission Tomography
  • Alzheimer Disease/diagnostic imaging
  • Cognitive Dysfunction/diagnostic imaging

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