Disrupted pathways from limbic areas to thalamus in schizophrenia highlighted by whole-brain resting-state effective connectivity analysis

Minghui Hua; Yanmin Peng; Yuan Zhou; Wen Qin; Chunshui Yu; Meng Liang

doi:10.1016/j.pnpbp.2019.109837

Disrupted pathways from limbic areas to thalamus in schizophrenia highlighted by whole-brain resting-state effective connectivity analysis

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20:99:109837. doi: 10.1016/j.pnpbp.2019.109837. Epub 2019 Dec 9.

Authors

Minghui Hua¹, Yanmin Peng¹, Yuan Zhou², Wen Qin³, Chunshui Yu⁴, Meng Liang⁵

Affiliations

¹ School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China.
² CAS Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
³ Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
⁴ School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
⁵ School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China. Electronic address: liangmeng@tmu.edu.cn.

PMID: 31830509
DOI: 10.1016/j.pnpbp.2019.109837

Abstract

Background: Numerous neuroimaging studies have revealed that schizophrenia was characterized by wide-spread dysconnection among brain regions during rest measured by functional connectivity (FC). In contrast with FC, effective connectivity (EC) provides information about directionality of brain connections and is thus valuable in mechanistic investigation of schizophrenic brain. However, a systematic characterization of whole-brain resting-state EC (rsEC) and how it captures different information compared with resting-state FC (rsFC) in schizophrenia are still lacking.

Aims: To systematically characterize the abnormalities of rsEC, compared with rsFC, in schizophrenia, and to test its discriminative power as a neuroimaging marker for schizophrenia diagnosis.

Method: Whole-brain rsEC and rsFC networks were constructed using resting-state fMRI data and compared between 103 patients with schizophrenia and 110 healthy participants. Pattern classifications between patients and controls based on whole-brain rsEC and rsFC were further performed using multivariate pattern analysis.

Results: We identified 17 rsEC significantly disrupted (mostly decreased) in patients, among which all were associated with the thalamus and 15 were from limbic areas (including hippocampus, parahippocampus and cingulate cortex) to the thalamus. In contrast, abnormal rsFC were widely distributed in the whole brain. The classification accuracies for distinguishing patients and controls using whole-brain rsEC and rsFC patterns were 78.6% and 82.7%, respectively, and was further improved to 84.5% when combining rsEC and rsFC.

Conclusions: Schizophrenia is featured by disrupted 'limbic areas-to-thalamus' rsEC, in contrast with diffusively altered rsFC. Moreover, both rsEC and rsFC contain valuable and complementary information which may be used as diagnostic markers for schizophrenia.

Keywords: Functional MRI; Functional connectivity; Granger causality; Multivariate pattern analysis; Pattern classification.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Female
Humans
Limbic System / diagnostic imaging*
Limbic System / physiopathology
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Nerve Net / diagnostic imaging*
Nerve Net / physiopathology
Neural Pathways / diagnostic imaging
Neural Pathways / physiopathology
Rest* / physiology
Schizophrenia / diagnostic imaging*
Schizophrenia / physiopathology
Thalamus / diagnostic imaging*
Thalamus / physiopathology
Young Adult