routes of pathologic change toward regular or random patterns , which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia

Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 ageand sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two Contract grant sponsor: Taipei Veterans General Hospital, Taiwan; Contract grant numbers: VGHUST100-G1-4-1; VGHUST102G1-2-1; V99ER3-004; V100C-013; Contract grant sponsor: the Taipei Veterans General Hospital-National Yang-Ming University Excellent Physician Scientists Cultivation Program; Contract grant number: 103-V-A-002; Contract grant sponsor: the Ministry of Science and Technology (MOST) of Taiwan; Contract grant numbers: MOST 101-2314-B-075-041-MY3; MOST 103-2320-B-008-001; Contract grant sponsor: the MOST support for the Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan; Contract grant number: MOST 103-2911-I008-001 *Correspondence to: Dr. Albert C. Yang; Department of Psychiatry, Taipei Veterans General Hospital, No 201, Sec 2. Shi-Pai Rd. Taipei, 11217, Taiwan. E-mail: accyang@gmail.com Received for publication 1 October 2014; Revised 27 January 2015; Accepted 30 January 2015. DOI: 10.1002/hbm.22763 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). r Human Brain Mapping 00:00–00 (2015) r VC 2015 Wiley Periodicals, Inc. routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia. Hum Brain Mapp 00:000– 000, 2015. VC 2015 Wiley Periodicals, Inc.