The complexity of the human brain's activity and connectivity varies over temporal scales and is altered in disease states such as schizophrenia. Using a multi-level analysis of spontaneous low-frequency fMRI data stretching from the activity of individual brain regions to the coordinated connectivity pattern of the whole brain, we investigate the role of brain signal complexity in schizophrenia. Specifically, we quantitatively characterize the univariate wavelet entropy of regional activity, the bivariate pairwise functional connectivity between regions, and the multivariate network organization of connectivity patterns. Our results indicate that univariate measures of complexity are less sensitive to disease state than higher level bivariate and multivariate measures. While wavelet entropy is unaffected by disease state, the magnitude of pairwise functional connectivity is significantly decreased in schizophrenia and the variance is increased. Furthermore, by considering the network structure as a function of correlation strength, we find that network organization specifically of weak connections is strongly correlated with attention, memory, and negative symptom scores and displays potential as a clinical biomarker, providing up to 75% classification accuracy and 85% sensitivity. We also develop a general statistical framework for the testing of group differences in network properties, which is broadly applicable to studies where changes in network organization are crucial to the understanding of brain function.
Bibliographical noteFunding Information:
D.S.B. was supported by the David and Lucile Packard Foundation, PHS Grant NS44393 and the Institute for Collaborative Biotechnologies through contract no. W911NF-09-D-0001 from the U.S. Army Research Office. Additional support for this research was provided by the National Institute of Mental Health (R01MH060662), Training Grant T32DA007097 for J.C., and the Center for Magnetic Resonance Research (BTRR P41 RR008079 and NCC grant P30 NS057091).
- Functional connectivity
- Graph theory
- Network analysis
- Resting state