%0 Journal Article
%T Siamese Graph Convolutional Network quantifies increasing structure-function discrepancy over the cognitive decline continuum.
%A Gamgam G
%A Yıldırım Z
%A Kabakçıoğlu A
%A Gurvit H
%A Demiralp T
%A Acar B
%J Comput Methods Programs Biomed
%V 254
%N 0
%D 2024 Jun 22
%M 38954916
%F 7.027
%R 10.1016/j.cmpb.2024.108290
%X <B>OBJECTIVE: </B>Alzheimer's disease dementia (ADD) is well known to induce alterations in both structural and functional brain connectivity. However, reported changes in connectivity are mostly limited to global/local network features, which have poor specificity for diagnostic purposes. Following recent advances in machine learning, deep neural networks, particularly Graph Neural Network (GNN) based approaches, have found applications in brain research as well. The majority of existing applications of GNNs employ a single network (uni-modal or structure/function unified), despite the widely accepted view that there is a nontrivial interdependence between the brain's structural connectivity and the neural activity patterns, which is hypothesized to be disrupted in ADD. This disruption is quantified as a discrepancy score by the proposed "structure-function discrepancy learning network" (sfDLN) and its distribution is studied over the spectrum of clinical cognitive decline. The measured discrepancy score is utilized as a diagnostic biomarker and is compared with state-of-the-art diagnostic classifiers.<BR><B>METHODS: </B>sfDLN is a GNN with a siamese architecture built on the hypothesis that the mismatch between structural and functional connectivity patterns increases over the cognitive decline spectrum, starting from subjective cognitive impairment (SCI), passing through a mid-stage mild cognitive impairment (MCI), and ending up with ADD. The structural brain connectome (sNET) built using diffusion MRI-based tractography and the novel, sparse (lean) functional brain connectome (ℓNET) built using fMRI are input to sfDLN. The siamese sfDLN is trained to extract connectome representations and a discrepancy (dissimilarity) score that complies with the proposed hypothesis and is blindly tested on an MCI group.<BR><B>RESULTS: </B>The sfDLN generated structure-function discrepancy scores show high disparity between ADD and SCI subjects. Leave-one-out experiments of SCI-ADD classification over a cohort of 42 subjects reach 88% accuracy, surpassing state-of-the-art GNN-based classifiers in the literature. Furthermore, a blind assessment over a cohort of 46 MCI subjects confirmed that it captures the intermediary character of the MCI group. GNNExplainer module employed to investigate the anatomical determinants of the observed discrepancy confirms that sfDLN attends to cortical regions neurologically relevant to ADD.<BR><B>CONCLUSIONS: </B>In support of our hypothesis, the harmony between the structural and functional organization of the brain degrades with increasing cognitive decline. This discrepancy, shown to be rooted in brain regions neurologically relevant to ADD, can be quantified by sfDLN and outperforms state-of-the-art GNN-based ADD classification methods when used as a biomarker.