Dataset Information

Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection syndrome." Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD.

SUBMITTER: Palesi F

PROVIDER: S-EPMC5013043 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

Palesi Fulvia F Castellazzi Gloria G Casiraghi Letizia L Sinforiani Elena E Vitali Paolo P Gandini Wheeler-Kingshott Claudia A M CA D'Angelo Egidio E

Frontiers in neuroscience 20160907

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functiona ...[more]

PMID: 27656119

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Project description:BackgroundA multimodal connectomic analysis using diffusion and functional MRI can provide complementary information on the structure-function network dynamics involved in complex neurodegenerative network disorders such as Parkinson's disease (PD). Deep learning-based graph neural network models generate higher-level embeddings that could capture intricate structural and functional regional interactions related to PD.ObjectiveThis study aimed at investigating the role of structure-function connections in predicting PD, by employing an end-to-end graph attention network (GAT) on multimodal brain connectomes along with an interpretability framework.MethodsThe proposed GAT model was implemented to generate node embeddings from the structural connectivity matrix and multimodal feature set containing morphological features and structural and functional network features of PD patients and healthy controls. Graph classification was performed by extracting topmost node embeddings, and the interpretability framework was implemented using saliency analysis and attention maps. Moreover, we also compared our model with unimodal models as well as other state-of-the-art models.ResultsOur proposed GAT model with a multimodal feature set demonstrated superior classification performance over a unimodal feature set. Our model demonstrated superior classification performance over other comparative models, with 10-fold CV accuracy and an F1 score of 86% and a moderate test accuracy of 73%. The interpretability framework highlighted the structural and functional topological influence of motor network and cortico-subcortical brain regions, among which structural features were correlated with onset of PD. The attention maps showed dependency between large-scale brain regions based on their structural and functional characteristics.ConclusionMultimodal brain connectomic markers and GAT architecture can facilitate robust prediction of PD pathology and provide an attention mechanism-based interpretability framework that can highlight the pathology-specific relation between brain regions.

Dataset Information

Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

Publications

Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

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