Functional Brain Network Disruptions in Parkinson’s Disease: Insights from Information Theory and Machine Learning

<b>Objectives:</b> This study investigates disruptions in functional brain networks in Parkinson's Disease (PD), using advanced modeling and machine learning. Functional networks were constructed using the Nonlinear Autoregressive Distributed Lag (NARDL) model, which captures nonlinear and asymmetric dependencies between regions of interest (ROIs). Key network metrics and information-theoretic measures were extracted to classify PD patients and healthy controls (HC), using deep learning models, with explainability methods employed to identify influential features. <b>Methods:</b> Resting-state fMRI data from the Parkinson's Progression Markers Initiative (PPMI) dataset were used to construct NARDL-based networks. Metrics, such as Degree, Closeness, Betweenness, and Eigenvector Centrality, along with Network Entropy and Complexity, were analyzed. Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), and Long Short-Term Memory (LSTM) models, classified PD and HC groups. Explainability techniques, including SHAP and LIME, identified significant features driving the classifications. <b>Results:</b> PD patients showed reduced Closeness (22%) and Betweenness Centrality (18%). CNN achieved 91% accuracy, with Network Entropy and Eigenvector Centrality identified as key features. Increased Network Entropy indicated heightened randomness in PD brain networks. <b>Conclusions:</b> NARDL-based analysis with interpretable deep learning effectively distinguishes PD from HC, offering insights into neural disruptions and potential personalized treatments for PD.