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Whole-Brain Static Functional Connectivity Disruptions Based on the Default Mode Network in Patients with Mild Cognitive Impairment

Yan Zeng, Yongjia Shao, Di Zhou, Mingjuan Qiu, Zijian Wang, Qian Xi

Brain Topography March 27, 2026 DOI: 10.1007/s10548-026-01187-6 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 62
Population Patients with mild cognitive impairment (MCI) and matched healthy controls
Measures MoCA
Topics Default mode network
Key findings Compared with healthy controls, MCI patients showed both increased and decreased static functional connectivity between DMN subregions and multiple brain regions, with decreased connectivity more widely distributed. The SFC value between the right angular gyrus and right insula was significantly negatively correlated with MoCA scores (r = -0.385), suggesting altered DMN interactions are associated with episodic memory disturbance.

Abstract

Mild cognitive impairment (MCI) is regarded a potential early stage of Alzheimer’s disease (AD) and associated with a significantly increased risk of progression to AD. This study aims to evaluate whole-brain static functional connectivity (SFC) disruptions with the default mode network (DMN) seed points in patients with MCI by resting-state functional magnetic resonance imaging (rs-fMRI), and to explore whether these disruptions could serve as potential markers for MCI progression to AD. Retrospective rs-fMRI data with MCI (n = 36) and corresponding matched healthy controls (HCs) (n = 26) were collected for comparison. Independent component analysis (ICA) was used to extract DMN regions, and SFC was calculated for four seed points within the DMN. Two-sample t-tests were performed to compare group differences in SFC strength between the MCI and HC groups, and Pearson correlation analyses were conducted. Compared to HCs, the MCI group showed both increased and decreased SFC between four subregions and multiple brain regions, decreased SFC was more widely distributed than increased SFC. Abnormal connectivity was more prominent in the first two key nodes compared to the latter two. Affected regions primarily located in the precuneus, frontal gyri, temporal gyri, postcentral gyrus, caudate nucleus, lingual gyrus, and fusiform gyrus. The SFC value between the right angular gyrus and the right insula was significantly negatively correlated with MoCA scores (r = − 0.385, p < 0.05, FDR-corrected). It reveals a decline in the functional integration capacity within the DMN, as well as complex reorganization and abnormal connectivity patterns between the DMN and other brain networks. The altered interactions between DMN subregions and abnormal brain areas are significantly associated with episodic memory disturbance in MCI. Supplementary Information The online version contains supplementary material available at 10.1007/s10548-026-01187-6.

Comparable studies

Other observational and cohort studies on default mode network, most cited first.

Study Year Design Participants
A default mode of brain function Normal adult human brain 2001 Observational study
Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Healthy subjects 2008 Observational cohort
Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls 2005 Observational cohort n = 20
Meditation experience is associated with differences in default mode network activity and connectivity Experienced meditators and matched meditation-naive controls 2011 Observational cohort
The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis Healthy subjects 2008 Observational study

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