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

OBJECTIVE: 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. METHOD: 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. RESULT: 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%). SIGNIFICANCE: These findings suggest that our spectral-based causality measure can improve classification performance and reveal useful network biomarkers of Parkinson's disease.

Betweenness Centrality in Resting-State Functional Networks Distinguishes Parkinson's Disease.

The goal of this paper is to use graph theory network measures derived from non-invasive electroencephalography (EEG) to develop neural decoders that can differentiate Parkinson's disease (PD) patients from healthy controls (HC). EEG signals from 27 patients and 27 demographically matched controls from New Mexico were analyzed by estimating their functional networks. Data recorded from the patients during ON and OFF levodopa sessions were included in the analysis for comparison. We used betweenness centrality of estimated functional networks to classify the HC and PD groups. The classifiers were evaluated using leave-one-out cross-validation. We observed that the PD patients (on and off medication) could be distinguished from healthy controls with 89% accuracy - approximately 4% higher than the state-of-the-art on the same dataset. This work shows that brain network analysis using extracranial resting-state EEG can discover patterns of interactions indicative of PD. This approach can also be extended to other neurological disorders.

Decoding Human Cognitive Control Using Functional Connectivity of Local Field Potentials.

Many patients with mental illnesses characterized by impaired cognitive control have no relief from gold-standard clinical treatments resulting in a pressing need for new alternatives. This paper develops a neural decoder to detect task engagement in ten human subjects during a conflict-based behavioral task known as the multi-source interference task (MSIT). Task engagement is of particular interest here because closed-loop brain stimulation during those states can augment decision-making. The functional connectivity patterns of the electrodes are extracted. A principal component analysis of these patterns is carried out and the ranked principal components are used as inputs to train subject-specific linear support vector machine classifiers. In this paper, we show that task engagement can be differentiated from background brain activity with a median accuracy of 89.7%. This was accomplished by constructing distributed functional networks from local field potentials recording during the task performance. A further challenge is that goal-directed efforts take place over higher temporal resolution. Task engagement must thus be detected at a similar rate for proactive intervention. We show that our algorithms can detect task engagement from neural recordings in less than 2 seconds; this can be further improved using an application-specific device.

Spectral Features Based Decoding of Task Engagement: The Role of Theta and High Gamma Bands in Cognitive Control.

This paper analyzes local field potentials (LFP) from 10 human subjects to discover frequency-dependent biomarkers of cognitive conflict. We utilize cortical and sub-cortical LFP recordings from the subjects during a cognitive task known as the Multi-Source Interference Task (MSIT). We decode the task engagement and discover biomarkers that may facilitate closed-loop neuromodulation to enhance cognitive control. First, we show that spectral power features in predefined frequency bands can be used to classify task and non-task segments with a median accuracy of 88.1%. Here the features are first ranked using the Bayes Factor and then used as inputs to subject-specific linear support vector machine classifiers. Second, we show that theta (4-8 Hz) band, and high gamma (65-200 Hz) band oscillations are modulated during the task performance. Third, by isolating time-series from specific brain regions of interest, we observe that a subset of the dorsolateral prefrontal cortex features is sufficient to decode the task states. The paper shows that cognitive control evokes robust neurological signatures, especially in the prefrontal cortex (PFC).

Region-Level Functional and Effective Network Analysis of Human Brain During Cognitive Task Engagement.

Mental disorders are a major source of disability, with few effective treatments. It has recently been argued that these diseases might be effectively treated by focusing on decision-making, and specifically remediating decision-making deficits that act as "ingredients" in these disorders. Prior work showed that direct electrical brain stimulation can enhance human cognitive control, and consequently decision-making. This raises a challenge of detecting cognitive control lapses directly from electrical brain activity. Here, we demonstrate approaches to overcome that challenge. We propose a novel method, referred to as maximal variance node merging (MVNM), that merges nodes within a brain region to construct informative inter-region brain networks. We employ this method to estimate functional (correlational) and effective (causal) networks using local field potentials (LFP) during a cognitive behavioral task. The effective networks computed using convergent cross mapping differentiate task engagement from background neural activity with 85% median classification accuracy. We also derive task engagement networks (TENs): networks that constitute the most discriminative inter-region connections. Subsequent graph analysis illustrates the crucial role of the dorsolateral prefrontal cortex (dlPFC) in task engagement, consistent with a widely accepted model for cognition. We also show that task engagement is linked to prefrontal cortex theta (4-8 Hz) oscillations. We, therefore, identify objective biomarkers associated with task engagement. These approaches may generalize to other cognitive functions, forming the basis of a network-based approach to detecting and rectifying decision deficits.