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Failed cooperative, but not competitive, interaction between large-scale brain networks impairs working memory in schizophrenia

Published online by Cambridge University Press:  08 January 2016

W. Pu
Affiliation:
Medical Psychological Institute, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
Q. Luo
Affiliation:
School of Life Sciences, Fudan University, Shanghai, People's Republic of China Centre for Computational Systems Biology, School of Mathematical Sciences, Fudan University, Shanghai, People's Republic of China
L. Palaniyappan
Affiliation:
Department of Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
Z. Xue
Affiliation:
Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
S. Yao
Affiliation:
Medical Psychological Institute, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
J. Feng*
Affiliation:
School of Life Sciences, Fudan University, Shanghai, People's Republic of China Centre for Computational Systems Biology, School of Mathematical Sciences, Fudan University, Shanghai, People's Republic of China Shanghai Center for Mathematical Sciences, Shanghai, People's Republic of China Department of Computer Science, University of Warwick, Coventry, UK Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, People's Republic of China
Z. Liu*
Affiliation:
Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China The State Key Laboratory of Medical Genetics, Central South University, People's Republic of China
*
*Addresses for correspondence: Z. Liu, M.D., Ph.D., Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha 410011, People's Republic of China; J. Feng, Ph.D., School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China. (Email: [email protected]) [Z.L.] (Email: [email protected]) [J.F.]
*Addresses for correspondence: Z. Liu, M.D., Ph.D., Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha 410011, People's Republic of China; J. Feng, Ph.D., School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China. (Email: [email protected]) [Z.L.] (Email: [email protected]) [J.F.]

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.

Method

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.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2016 

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