Salience-default mode functional network connectivity linked to positive and negative symptoms of schizophrenia

Stephanie M. Hare, Judith M. Ford, Daniel H. Mathalon, Eswar Damaraju, Juan Bustillo, Aysenil Belger, Hyo Jong Lee, Bryon A. Mueller, Kelvin O. Lim, Gregory G. Brown, Adrian Preda, Theo G.M. Van Erp, Steven G. Potkin, Vince D. Calhoun, Jessica A. Turner

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Schizophrenia is a complex, debilitating mental disorder characterized by wide-ranging symptoms including delusions, hallucinations (so-called positive symptoms), and impaired motor and speech/language production (so-called negative symptoms). Salience-monitoring theorists propose that abnormal functional communication between the salience network (SN) and default mode network (DMN) begets positive and negative symptoms of schizophrenia, yet prior studies have predominately reported links between disrupted SN/DMN functional communication and positive symptoms. It remains unclear whether disrupted SN/ DMN functional communication explains (1) solely positive symptoms or (2) both positive and negative symptoms of schizophrenia. To address this question, we incorporate time-lag-shifted functional network connectivity (FNC) analyses that explored coherence of the resting-state functional magnetic resonance imaging signal of 3 networks (anterior DMN, posterior DMN, and SN) with fixed time lags introduced between network time series (1 TR = 2 s; 2 TR = 4 s). Multivariate linear regression analysis revealed that severity of disordered thought and attentional deficits were negatively associated with 2 TR-shifted FNC between anterior DMN and posterior DMN. Meanwhile, severity of flat affect and bizarre behavior were positively associated with 1 TR-shifted FNC between anterior DMN and SN. These results provide support favoring the hypothesis that lagged SN/DMN functional communication is associated with both positive and negative symptoms of schizophrenia.

Original languageEnglish (US)
Pages (from-to)892-901
Number of pages10
JournalSchizophrenia bulletin
Issue number4
StatePublished - Jun 18 2019

Bibliographical note

Funding Information:
Functional Biomedical Informatics Research Network was supported by a grant from National Center for Research Resources to Potkin (1U24 RR021992). This work was supported in part through a Provost Dissertation Fellowship to Hare, and by a grant from National Institute of Mental Health to Turner and Calhoun (1R01MH094524). Dr Mathalon has served as a consultant for Boehringer Ingelheim, Alkermes, Takeda, and Upsher-Smith. All other authors have declared no conflicts of interest.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


  • Default mode network
  • ICA
  • Negative symptoms
  • Positive symptoms
  • Resting-state fMRI
  • Salience network


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