Research articleDecreased middle temporal gyrus connectivity in the language network in schizophrenia patients with auditory verbal hallucinations
Introduction
Schizophrenia (SZ) is a serious mental disorder that associates with abnormalities of brain structure and functions [1], [2], [3]. As important indicators to evaluate the severity and clinical efficacy of schizophrenia, auditory verbal hallucinations (AVHs) are the most common symptoms of SZ, with an incidence of 60%–80% [4].
SZ is a disorder with unknown etiology and pathophysiology that are further complicated than regional brain abnormalities. Previous neuroimaging studies on AVHs have revealed structural and functional alterations in the language network. A diffusion tensor imaging (DTI) study revealed reduced integrity of the fiber connecting frontal and temporo-parietal language regions [5]. It was further supported by neuroimaging studies revealing that AVHs in SZ was associated with dysconnectivity in the language network [6]. A study of fMRI showed that the emergence of AVHs was the result of mild disruption of function connectivity along the fronto-temporal pathway [7]. Reduced fronto-temporal functional connectivity has also been demonstrated in SZ patients with AVHs during sentence-completion task [8], external speech processing [9], and speaking aloud task [10]. A resting state fMRI study showed that disrupted intrinsic connectivity of the language network could underlie persistent AVHs in patients with SZ [11].
Although the above studies have indicated that the emergence of AVHs is associated with altered structural and functional connectivity within the language network, it still remains unclear how these regions interact with each other to cause the symptoms like AVHs in SZ. As a powerful tool for effective connectivity (describes the causal influences that one region exerts over another [12]) analysis, dynamic causal modeling (DCM) [13] not only enable us to quantify the strength of the connections, but also demonstrate directed information flow from one region to another, therefore provide more information to recover the underlying neural substrates of AVHs and SZ. In fact, there have been some attempts to study abnormal effective connectivity in SZ patients using DCM [9], [14], [15]. Ćurčić-Blake et al. found that increased effective connectivity from the posterior cingulate cortex to the ventromedial prefrontal cortex was associated with poorer insight [16]. In addition, abnormal effective connectivity of the posterior cingulate and medial prefrontal cortices have also been related to working memory impairments [17]. Interestingly, measures of effective connectivity have been used to explain differences in the perception of the hollow-mask illusion [18]. However, it still remains unknown how regions in the language network interact with each other abnormally in SZ patients with AVHs.
In this study, we aimed to investigate resting-state effective connectivity within the language network in 18 SZ patients with AVHs, 18 patients without AVHs and 37 healthy controls using DCM. Three regions including the left inferior frontal gyrus (LIFG), left middle temporal gyrus (LMTG), and left inferior parietal lobule (LIPL) were selected as regions of interest (ROIs) according to previous findings [19], [20]. We hypothesized that the effective connectivity within the language network would be altered in SZ patients with AVHs.
Section snippets
Subjects
This study was approved by the Institutional Board of The Fourth Military Medical University. All participants received a full comprehensive description of the MRI study and gave voluntarily written informed consent before entering the study. A total of 73 subjects were recruited (36 patients with schizophrenia and 37 healthy controls). All patients fulfilled the DSM-IV [21] diagnostic criteria for schizophrenia and was further divided into the AVH(18 subjects) and nAVH group(18 subjects) based
Results
Fig. 1 shows the effective connectivity of the language network in the AVH group, nAVH group and controls, respectively (one-sample t-test at p < 0.05, Bonferroni corrected for multiple comparisons). One way ANOVA (p < 0.05) showed that the effective connection from LIFG to LMTG (p = 0.000) and the effective connection from LIPL to LMTG (p = 0.000) were significantly different among the three groups.
Fig. 2 illustrates changes in effective connectivity in the patients group (post-hoc t-tests, p < 0.05).
Discussion
In this study, we observed decreased effective connection from LIPL to LMTG in both patient groups compared to healthy controls. These findings provide a piece of evidence for the “dysconnection hypothesis” of SZ. On the one hand, decreased effective connectivity found in the current study provides further support for previous neuroimaging studies that have reported impaired temporo-parietal functional and structural connectivity. On the other hand, the directionality of the connections that
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
HW, HL and QT designed the experiment; HW, QT and HY recruited the subjects and collected the fMRI images; LZ, BL, LL, WL and YL analyzed the data; LZ, BL, QL, XB and HL prepared the manuscript.
Acknowledgements
This work was supported by the National Natural Science Foundation of China [81301199, 81630032, 81230035 and 81071220]. We thank anonymous reviewers for guidance in clarifying and elaborating this report.
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These authors contributed equally.