title: Altered global brain signal in schizophrenia.
abstract: Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia.
authors.affiliation: Department of Psychiatry andInterdepartmental Neuroscience Program, Yale University, New Haven, CT 06511;Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519;
authors.forename: Genevieve J
authors.initials: GJ
authors.lastname: Yang
authors.affiliation: Center for Neural Science, New York University, New York, NY 06510;
authors.forename: John D
authors.initials: JD
authors.lastname: Murray
authors.affiliation: Department of Psychology, University of Ljubljana, 1000 Ljubljana, Slovenia;
authors.forename: Grega
authors.initials: G
authors.lastname: Repovs
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102;
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cole
authors.affiliation: Department of Psychiatry andAbraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519;University Psychiatric Hospital Vrapce, University of Zagreb, Zagreb 10000, Croatia;
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Savic
authors.affiliation: Department of Anatomy and Neurobiology, Washington University in St. Louis, MO 63130;
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Glasser
authors.affiliation: Department of Psychiatry andInterdepartmental Neuroscience Program, Yale University, New Haven, CT 06511;Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519;Department of Psychology, Yale University, New Haven, CT 06520;
authors.forename: Christopher
authors.initials: C
authors.lastname: Pittenger
authors.affiliation: Department of Psychiatry andAbraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519;National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06519;
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: Center for Neural Science, New York University, New York, NY 06510;New York University-East China Normal University Joint Institute of Brain and Cognitive Science, New York University, Shanghai, China; and.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Psychiatry andDepartment of Neurobiology, Yale University School of Medicine, New Haven, CT 06511;Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Department of Psychiatry andOlin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Department of Psychiatry andInterdepartmental Neuroscience Program, Yale University, New Haven, CT 06511;Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519;Department of Psychology, Yale University, New Haven, CT 06520;National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06519; alan.anticevic@yale.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Anticevic
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D016022:Case-Control Studies; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D010100:Oxygen
keywords: global signal; psychiatric illness; resting-state