Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia
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Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.
KeywordsResting-state fMRI Effective connectivity Schizophrenia Spectral dynamic causal modeling Working memory deficit
We thank all patients and controls for their study participation. We are very grateful to Drs. Rhoda E. and Edmund F. Perozzi for English and content editing assistance and discussions. This work was supported by National Basic Research Program of China (Grant No. 2011CB707800), National Natural Science Foundation of China (Grant No. 91132301), Youth Innovation Promotion Association of Chinese Academy of Sciences (Grant No. 2012075), Plan A of Science and Technology Support Program from Science and Technology Department of Sichuan Province (Grand no. 2014SZ0014), and Natural Science Foundation of Hubei Province (Grant No. 2014CFB732).
Compliance with ethical standards
All procedures performed in this study of human participants were in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all the participants. The study was approved by the Medical Research Ethics Committee of Renmin Hospital of Wuhan University, People’s Republic of China.
Conflict of interest
The authors declare that they have no conflict of interest.
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