Dataset Information

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

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.

SUBMITTER: Maleki Balajoo S

PROVIDER: S-EPMC9250470 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer's disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS (p = 0.047) and glucose hypometabolism (p = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients (p = 0.011) and in V_pcu for both MCI (p = 0.006) and AD (p = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects (p = 0.038) and in V_pcu of AD patients compared to both MCI patients (p = 0.045) and CN subjects (p < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS (r = 0.498, p = 0.042) and hypometabolism (r = 0.566, p = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.