Effective Brain Connectivity Extraction by Frequency-Domain Convergent Cross-Mapping (FDCCM) and Its Application in Parkinson's Disease Classification.

Abstract

Inferring causal or effective connectivity between measured timeseries is crucial to understanding directed interactions in complex systems. This task is especially challenging in the brain as the underlying dynamics are not well-understood. This paper aims to introduce a novel causality measure called frequency-domain convergent cross-mapping (FDCCM) that utilizes frequency-domain dynamics through nonlinear state-space reconstruction. Using synthesized chaotic timeseries, we investigate general applicability of FDCCM at different causal strengths and noise levels. We also apply our method on two resting-state Parkinson's datasets with 31 and 54 subjects, respectively. To this end, we construct causal networks, extract network features, and perform machine learning analysis to distinguish Parkinson's disease patients (PD) from age and gender-matched healthy controls (HC). Specifically, we use the FDCCM networks to compute the betweenness centrality of the network nodes, which act as features for the classification models. The analysis on simulated data showed that FDCCM is resilient to additive Gaussian noise, making it suitable for real-world applications. Our proposed method also decodes scalp-EEG signals to classify the PD and HC groups with approximately 97% leave-one-subject-out cross-validation accuracy. We compared decoders from six cortical regions to find that features derived from the left temporal lobe lead to a higher classification accuracy of 84.5% compared to other regions. Moreover, when the classifier trained using FDCCM networks from one dataset was tested on an independent out-of-sample dataset, it attained an accuracy of 84%. This accuracy is significantly higher than correlational networks (45.2%) and CCM networks (54.84%). These findings suggest that our spectral-based causality measure can improve classification performance and reveal useful network biomarkers of Parkinson's disease.