Nonlinear Functional Connectivity Network Recovery in the Human Brain with Mutual Connectivity Analysis (MCA): Convergent Cross-Mapping and Non-Metric Clustering.

We explore a computational framework for functional connectivity analysis in resting-state functional MRI (fMRI) data acquired from the human brain for recovering the underlying network structure and understanding causality between network components. Termed mutual connectivity analysis (MCA), this framework involves two steps, the first of which is to evaluate the pair-wise cross-prediction performance between fMRI pixel time series within the brain. In a second step, the underlying network structure is subsequently recovered from the affinity matrix using non-metric network clustering approaches, such as the so-called Louvain method. Finally, we use convergent cross-mapping (CCM) to study causality between different network components. We demonstrate our MCA framework in the problem of recovering the motor cortex network associated with hand movement from resting state fMRI data. Results are compared with a ground truth of active motor cortex regions as identified by a task-based fMRI sequence involving a finger-tapping stimulation experiment. Our results regarding causation between regions of the motor cortex revealed a significant directional variability and were not readily interpretable in a consistent manner across subjects. However, our results on whole-slice fMRI analysis demonstrate that MCA-based model-free recovery of regions associated with the primary motor cortex and supplementary motor area are in close agreement with localization of similar regions achieved with a task-based fMRI acquisition. Thus, we conclude that our MCA methodology can extract and visualize valuable information concerning the underlying network structure between different regions of the brain in resting state fMRI.