Abstract

BackgroundThe brain’s dynamic spontaneous neural activity and dynamic functional connectivity (dFC) are both important in supporting cognition, but how these two types of brain dynamics evolve and co-evolve in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remain unclear. The aim of the present study was to investigate recurrent and concurrent patterns of two types of dynamic brain states correlated with cognitive decline.MethodsThe present study analyzed resting-state functional magnetic resonance imaging data from 62 SCD patients, 75 MCI patients, and 70 healthy controls (HCs). We used the sliding-window and clustering method to identify two types of recurrent brain states from both dFC and dynamic regional spontaneous activity, as measured by dynamic fractional amplitude of low-frequency fluctuations (dfALFF). Then, the occurrence frequency of a dFC or dfALFF state and the co-occurrence frequency of a pair of dFC and dfALFF states among all time points are extracted for each participant to describe their dynamics brain patterns.ResultsWe identified a few recurrent states of dfALFF and dFC and further ascertained the co-occurrent patterns of these two types of dynamic brain states (i.e., dfALFF and dFC states). Importantly, the occurrence frequency of a default-mode network (DMN)-dominated dFC state was significantly different between HCs and SCD patients, and the co-occurrence frequencies of a DMN-dominated dFC state and a DMN-dominated dfALFF state were also significantly different between SCD and MCI patients. These two dynamic features were both significantly positively correlated with Mini-Mental State Examination scores.ConclusionOur findings revealed novel fMRI-based neural signatures of cognitive decline from recurrent and concurrent patterns of dfALFF and dFC, providing strong evidence supporting SCD as the transition phase between normal aging and MCI. This finding holds potential to differentiate SCD patients from HCs via both dFC and dfALFF as objective neuroimaging biomarkers, which may aid in the early diagnosis and intervention of Alzheimer’s disease.

Highlights

  • The brain’s dynamic spontaneous neural activity and dynamic functional connectivity are both important in supporting cognition, but how these two types of brain dynamics evolve and co-evolve in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remain unclear

  • We investigated recurrent dynamic fractional ALFF (fALFF) and dynamic functional connectivity (dFC) patterns, as well as the percentage of the time point of each state and the co-occurrence of each pair of these two types of states at all time points from resting-state functional magnetic resonance imaging (fMRI) recorded in SCD patients, MCI patients, and healthy controls (HCs)

  • The Geriatric Depression Scale (GDepS) scores were significantly different between SCD and MCI groups, as well as between HC and MCI groups

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Summary

Introduction

The brain’s dynamic spontaneous neural activity and dynamic functional connectivity (dFC) are both important in supporting cognition, but how these two types of brain dynamics evolve and co-evolve in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remain unclear. The aim of the present study was to investigate recurrent and concurrent patterns of two types of dynamic brain states correlated with cognitive decline. Subjective cognitive decline (SCD), which is considered as a risk state for AD [1, 2], has received increased attention. Because disruption of functional connectivity (FC) emerges at the earliest stage of AD, FC has been considered as a potential neural biomarker for early identification of functional alterations related to AD pathophysiology [3]. A previous study has demonstrated that dFC biomarkers may represent useful surrogate outcomes for the development of preclinical targeted therapeutic interventions [11]

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