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Updated: Jul 2, 2025

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
REPRESENTATIVE FUNCTIONAL CONNECTIVITY LEARNING FOR MULTIPLE CLINICAL GROUPS IN ALZHEIMER'S DISEASE
Lu Zhang1, Xiaowei Yu1, Yanjun Lyu1
1Computer Science and Engineering, The University of Texas at Arlington, Arlington, TX, USA.
Abstract:
Mild cognitive impairment (MCI) is a high-risk dementia condition which progresses to probable Alzheimer's disease (AD) at approximately 10% to 15% per year. Characterization of group-level differences between two subtypes of MCI - stable MCI (sMCI) and progressive MCI (pMCI) is the key step to understand the mechanisms of MCI progression and enable possible delay of transition from MCI to AD. Functional connectivity (FC) is considered as a promising way to study MCI progression since which may show alterations even in preclinical stages and provide substrates for AD progression. However, the representative FC patterns during AD development for different clinical groups, especially for sMCI and pMCI, have been understudied. In this work, we integrated autoencoder and multi-class classification into a single deep model and successfully learned a set of clinical group related feature vectors. Specifically, we trained two non-linear mappings which realized the mutual transformations between the original FC space and the feature space. By mapping the learned clinical group related feature vectors to the original FC space, representative FCs were constructed for each group. Moreover, based on these feature vectors, our model achieves a high classification accuracy - 68% for multi-class classification (NC vs SMC vs sMCI vs pMCI vs AD). Code has been released.
Insights
This study identifies distinct functional connectivity patterns in stable and progressive mild cognitive impairment (MCI) subtypes. Understanding these differences is crucial for potentially delaying the progression to Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Medical Imaging
- Artificial Intelligence in Medicine
Background:
- Mild cognitive impairment (MCI) is a precursor to Alzheimer's disease (AD), with 10-15% progressing annually.
- Differentiating stable MCI (sMCI) from progressive MCI (pMCI) is vital for understanding disease mechanisms and intervention.
- Functional connectivity (FC) alterations may indicate early-stage neurodegeneration relevant to MCI progression.
Purpose of the Study:
- To characterize group-level differences in functional connectivity (FC) between MCI subtypes (sMCI and pMCI).
- To identify representative FC patterns associated with different clinical groups, including normal cognition (NC), sMCI, pMCI, and AD.
- To develop a deep learning model for classifying these clinical groups based on FC features.
Main Methods:
- Integration of an autoencoder and multi-class classification into a single deep learning model.
- Training non-linear mappings for mutual transformations between the original FC space and a learned feature space.
- Construction of representative FCs for each clinical group by mapping learned feature vectors back to the FC space.
Main Results:
- Successfully learned clinical group-related feature vectors from functional connectivity data.
- Generated representative FC patterns specific to each clinical group (NC, SMC, sMCI, pMCI, AD).
- Achieved a multi-class classification accuracy of 68% for differentiating between NC, SMC, sMCI, pMCI, and AD.
Conclusions:
- The developed deep learning model effectively captures group-level FC differences relevant to MCI progression.
- Representative FC patterns can be constructed to visualize and understand neurobiological changes across clinical stages.
- This approach offers a promising avenue for early detection and differentiation of MCI subtypes, potentially aiding in Alzheimer's disease research.
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