Reconfiguration Of Dominant Coupling Modes In Mild Traumatic Brain Injury Mediated By δ-Band Activity: A Resting State MEG Study

During the last few years, rich-club (RC) organization has been studied as a possible brain-connectivity organization model for large-scale brain networks. At the same time, empirical and simulated data of neurophysiological models have demonstrated the significant role of intra-frequency and inter-frequency coupling among distinct brain areas. The current study investigates further the importance of these couplings using recordings of resting-state magnetoencephalographic activity obtained from 30 mild traumatic brain injury (mTBI) subjects and 50 healthy controls. Intra-frequency and inter-frequency coupling modes are incorporated in a single graph to detect group differences within individual rich-club subnetworks (type I networks) and networks connecting RC nodes with the rest of the nodes (type II networks). Our results show a higher probability of inter-frequency coupling for ({delta}-{gamma}1), ({delta}-{gamma}2), ({theta}-{beta}), ({theta}-{gamma}2), (-{gamma}2), ({gamma}1-{gamma}2) and intra-frequency coupling for ({gamma}1-{gamma}1) and ({delta}-{delta}) for both type I and type II networks in the mTBI group. Additionally, mTBI and control subjects can be correctly classified with high accuracy (98.6%), whereas a general linear regression model can effectively predict the subject group using the ratio of type I and type II coupling in the ({delta}, {theta}), ({delta}, {beta}), ({delta}, {gamma}1), and ({delta}, {gamma}2) frequency pairs. These findings support the presence of an RC organization simultaneously with dominant frequency interactions within a single functional graph. Our results demonstrate a hyperactivation of intrinsic RC networks in mTBI subjects compared to controls, which can be seen as a plausible compensatory mechanism for alternative frequency-dependent routes of information flow in mTBI subjects.