Permutation conditional mutual information to quantify TMS-evoked cortical connectivity in disorders of consciousness

Objective. To improve the understanding and diagnostic accuracy of disorders of consciousness (DOC) by quantifying transcranial magnetic stimulation (TMS) evoked electroencephalography connectivity using permutation conditional mutual information (PCMI). Approach. PCMI can characterize the functional connectivity between different brain regions. This study employed PCMI to analyze TMS-evoked cortical connectivity (TEC) in 154 DOC patients and 16 normal controls, focusing on optimizing parameter selection for PCMI (Data length, Order length, Time delay). We compared short-range and long-range PCMI values across different consciousness states-unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and normal (NOR)-and assessed various feature selection and classification techniques to distinguish these states. Main results. (1) PCMI can quantify TEC. We found optimal parameters to be Data length: 500 ms; Order: 3; Time delay: 6 ms. (2) TMS evoked potentials (TEPs) for NOR showed a rich response, while MCS patients showed only a few components, and UWS patients had almost no significant components. The values of PCMI connectivity metrics demonstrated its usefulness for measuring cortical connectivity evoked by TMS. From NOR to MCS to UWS, the number and strength of TEC decreased. Quantitative analysis revealed significant differences in the strength and number of TEC in the entire brain, local regions and inter-regions among different consciousness states. (3) A decision tree with feature selection by mutual information performed the best (balanced accuracy: 87.0% and accuracy: 83.5%). This model could accurately identify NOR (100.0%), but had lower identification accuracy for UWS (86.5%) and MCS (74.1%). Significance. The application of PCMI in measuring TMS-evoked connectivity provides a robust metric that enhances our ability to differentiate between various states of consciousness in DOC patients. This approach not only aids in clinical diagnosis but also contributes to the broader understanding of cortical connectivity and consciousness.