Altered resting state complexity in schizophrenia.
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.
Complex Systems Group, Department of Physics, University of California, Santa Barbara, CA 93106, United States. dbassett@physics.ucsb.edu
Danielle S
DS
Bassett
Brent G
BG
Nelson
Bryon A
BA
Mueller
Jazmin
J
Camchong
Kelvin O
KO
Lim
D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D001288:Attention / Q000502:physiology; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D003627:Data Interpretation, Statistical; D004522:Educational Status; D019277:Entropy; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012146:Rest / Q000502:physiology; D012559:Schizophrenia / Q000473:pathology*; D012565:Schizophrenic Psychology; D012984:Software; D060388:Support Vector Machine