Local functional connectivity abnormalities in mild cognitive impairment and Alzheimer's disease: A meta-analytic
Tommaso Costa1, Enrico Premi2, Barbara Borroni3
1GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, Turin, Italy; Functional Neuroimaging and Complex Neural Systems (FOCUS) Laboratory, Department of Psychology, University of Turin, Turin, Italy; Neuroscience Institute of Turin (NIT), Turin, Italy.
Abstract:
Functional magnetic resonance imaging research employing regional homogeneity (ReHo) analysis has uncovered aberrant local brain connectivity in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in comparison with healthy controls. However, the precise localization, extent, and possible overlap of these aberrations are still not fully understood. To bridge this gap, we applied a novel meta-analytic and Bayesian method (minimum Bayes Factor Activation Likelihood Estimation, mBF-ALE) for a systematic exploration of local functional connectivity alterations in MCI and AD brains. We extracted ReHo data via a standardized MEDLINE database search, which included 35 peer-reviewed experiments, 1,256 individuals with AD or MCI, 1,118 healthy controls, and 205 x-y-z coordinates of ReHo variation. We then separated the data into two distinct datasets: one for MCI and the other for AD. Two mBF-ALE analyses were conducted, thresholded at "very strong evidence" (mBF ≥ 150), with a minimum cluster size of 200 mm³. We also assessed the spatial consistency and sensitivity of our Bayesian results using the canonical version of the ALE algorithm. For MCI, we observed two clusters of ReHo decrease and one of ReHo increase. Decreased local connectivity was notable in the left precuneus (Brodmann area - BA 7) and left inferior temporal gyrus (BA 20), while increased connectivity was evident in the right parahippocampal gyrus (BA 36). The canonical ALE confirmed these locations, except for the inferior temporal gyrus. In AD, one cluster each of ReHo decrease and increase were found, with decreased connectivity in the right posterior cingulate cortex (BA 30 extending to BA 23) and increased connectivity in the left posterior cingulate cortex (BA 31). These locations were confirmed by the canonical ALE. The identification of these distinct functional connectivity patterns sheds new light on the complex pathophysiology of MCI and AD, offering promising directions for future neuroimaging-based interventions. Additionally, the use of a Bayesian framework for statistical thresholding enhances the robustness of neuroimaging meta-analyses, broadening its applicability to small datasets.
Insights
This study used a novel Bayesian meta-analysis to map brain connectivity changes in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Findings reveal distinct patterns of altered regional homogeneity (ReHo) in MCI and AD, offering insights into neuroimaging interventions.
Area of Science:
- Neuroscience
- Neuroimaging
- Cognitive Neurology
Background:
- Functional magnetic resonance imaging (fMRI) using regional homogeneity (ReHo) analysis has identified abnormal local brain connectivity in mild cognitive impairment (MCI) and Alzheimer's disease (AD).
- The precise locations, extent, and overlap of these connectivity aberrations in MCI and AD remain incompletely understood.
Purpose of the Study:
- To systematically explore local functional connectivity alterations in MCI and AD brains using a novel meta-analytic and Bayesian method (minimum Bayes Factor Activation Likelihood Estimation, mBF-ALE).
- To precisely map the localization and extent of ReHo variations in individuals with MCI and AD compared to healthy controls.
Main Methods:
- A meta-analysis of 35 peer-reviewed experiments (1,256 MCI/AD patients, 1,118 controls) was conducted using ReHo data extracted from the MEDLINE database.
- Two mBF-ALE analyses were performed on separate datasets for MCI and AD, thresholded at 'very strong evidence' (mBF ≥ 150) with a minimum cluster size of 200 mm³.
- Spatial consistency was assessed using the canonical ALE algorithm.
Main Results:
- For MCI, decreased ReHo was observed in the left precuneus (BA 7) and left inferior temporal gyrus (BA 20), while increased ReHo was found in the right parahippocampal gyrus (BA 36).
- For AD, decreased ReHo was identified in the right posterior cingulate cortex (BA 30/23), and increased ReHo in the left posterior cingulate cortex (BA 31).
- Canonical ALE confirmed most locations, highlighting the robustness of the Bayesian approach.
Conclusions:
- Distinct functional connectivity patterns in MCI and AD, identified through Bayesian meta-analysis of ReHo, provide new insights into their complex pathophysiology.
- These findings offer promising directions for future neuroimaging-based interventions targeting MCI and AD.
- The Bayesian framework enhances the reliability of neuroimaging meta-analyses, particularly for smaller datasets.
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