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Open Access Research article

Impaired coupling of local and global functional feedbacks underlies abnormal synchronization and negative symptoms of schizophrenia

Kyungchul Noh1, Kyung Soon Shin2, Dongkwan Shin1, Jae Yeon Hwang46, June Sic Kim3, Joon Hwan Jang5, Chun Kee Chung3, Jun Soo Kwon256* and Kwang-Hyun Cho1*

Author Affiliations

1 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

2 Clinical Cognitive Neuroscience Center, Neuroscience Institute, SNU-MRC, Seoul, Republic of Korea

3 MEG Center, Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea

4 Department of Psychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea

5 Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea

6 Department of Brain and Cognitive Sciences, World Class University Program, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea

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BMC Systems Biology 2013, 7:30  doi:10.1186/1752-0509-7-30

Published: 10 April 2013

Abstract

Background

Abnormal synchronization of brain oscillations is found to be associated with various core symptoms of schizophrenia. However, the underlying mechanism of this association remains yet to be elucidated.

Results

In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia. Analysis of the magnetoencephalography data obtained from patients with chronic schizophrenia during rest revealed an increase in beta band synchronization and a reduction in gamma band power compared to healthy controls. Using a feedback identification method based on non-causal impulse responses, we constructed functional feedback networks and found that CLGF circuits were significantly reduced in schizophrenia. From computational analysis on the basis of the Wilson-Cowan model, we unraveled that the CLGF circuits are critically involved in the abnormal synchronization and the dynamical switching between beta and gamma bands power in schizophrenia. Moreover, we found that the abundance of CLGF circuits was negatively correlated with the development of negative symptoms of schizophrenia, suggesting that the negative symptom is closely related to the impairment of this circuit.

Conclusions

Our study implicates that patients with schizophrenia might have the impaired coupling of inter- and intra-regional functional feedbacks and that the CLGF circuit might serve as a critical bridge between abnormal synchronization and the negative symptoms of schizophrenia.

Keywords:
Abnormal synchrony; Network topology; Coupled feedback; Schizophrenia; Negative symptom