title: Failed cooperative, but not competitive, interaction between large-scale brain networks impairs working memory in schizophrenia.
abstract: BACKGROUND
  A large-scale network named the default mode network (DMN) dynamically cooperates and competes with an external attention system (EAS) to facilitate various cognitive functioning that is prominently impaired in schizophrenia. However, it is unclear whether the cognitive deficit in schizophrenia is related to the disrupted competition and/or cooperation between these two networks.
  
  
  METHODS
  A total of 35 schizophrenia patients and 30 healthy controls were scanned using gradient-echo echo-planar imaging during n-back working memory (WM) processing. Brain activities of the DMN and EAS were measured using general linear modelling of the functional magnetic resonance imaging data. Dynamic interaction between the DMN and EAS was decomposed into two directions using Granger causality analysis.
  
  
  RESULTS
  We observed a significant failure of DMN suppression in patients with schizophrenia, which was significantly related to WM/attentional deficit. Granger causality modelling showed that in healthy controls, while the EAS inhibitorily influenced the DMN, the DMN exerted an 'excitatory' or cooperative influence back on the EAS, especially in those with lower WM accuracy. In schizophrenia, this 'excitatory' DMN→EAS influence within the reciprocal EAS-DMN loop was significantly reduced, especially in patients with WM/attentional deficit.
  
  
  CONCLUSIONS
  The dynamic interaction between the DMN and EAS is likely to be comprised of both competitive and cooperative influences. In healthy controls, both the 'inhibitory' EAS→DMN interaction and 'excitatory' DMN→EAS interaction are correlated with WM performance. In schizophrenia, reduced 'cooperative' influence from the DMN to dorsal nodes of the EAS occurs in the context of non-suppression of the DMN and may form a possible pathophysiological substrate of WM deficit and attention disorder.
authors.affiliation: Medical Psychological Institute,Second Xiangya Hospital,Central South University,Changsha,People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Pu
authors.affiliation: School of Life Sciences,Fudan University,Shanghai,People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Psychiatry,Schulich School of Medicine and Dentistry,University of Western Ontario,London,Ontario,Canada.
authors.forename: L
authors.initials: L
authors.lastname: Palaniyappan
authors.affiliation: Institute of Mental Health,Second Xiangya Hospital,Central South University,Changsha,People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Medical Psychological Institute,Second Xiangya Hospital,Central South University,Changsha,People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Yao
authors.affiliation: School of Life Sciences,Fudan University,Shanghai,People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.affiliation: Institute of Mental Health,Second Xiangya Hospital,Central South University,Changsha,People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D003071:Cognition; D017352:Echo-Planar Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008570:Memory, Short-Term; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000503:physiopathology*; D012919:Social Behavior; D055815:Young Adult
keywords: Default mode network; dynamic interaction; external attention system; schizophrenia; working memory