Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations (AVHs) in schizophrenia (SZ) remains unclear. In this study, we used stochastic dynamic causal modeling (sDCM) to quantify connections among the left dorsolateral prefrontal cortex (inner speech monitoring), auditory cortex (auditory processing), hippocampus (memory retrieval), thalamus (information filtering), and Broca's area (language production) in 17 first-episode drug-naïve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging. Finally, we performed receiver operating characteristic (ROC) analysis and correlation analysis between image measures and symptoms. sDCM revealed an increased sensitivity of auditory cortex to its thalamic afferents and a decrease in hippocampal sensitivity to auditory inputs in SZ patients with AVHs. The area under the ROC curve showed the diagnostic value of these two connections to distinguish SZ patients with AVHs from those without AVHs. Furthermore, we found a positive correlation between the strength of the connectivity from Broca's area to the auditory cortex and the severity of AVHs. These findings demonstrate, for the first time, augmented AVH-specific excitatory afferents from the thalamus to the auditory cortex in SZ patients, resulting in auditory perception without external auditory stimuli. Our results provide insights into the neural mechanisms underlying AVHs in SZ. This thalamic-auditory cortical-hippocampal dysconnectivity may also serve as a diagnostic biomarker of AVHs in SZ and a therapeutic target based on direct in vivo evidence.

IntroductionUnderstanding the neural basis underlying major depressive disorder (MDD) is essential for the diagnosis and treatment of this mental disorder. Aberrant activation and functional connectivity of the default mode network (DMN) have been consistently found in patients with MDD. It is not known whether effective connectivity within the DMN is altered in MDD.ObjectsThe primary object of this study is to investigate the effective connectivity within the DMN during resting state in MDD patients before and after eight weeks of antidepressant treatment.MethodsWe defined four regions of the DMN (medial frontal cortex, posterior cingulate cortex, left parietal cortex, and right parietal cortex) for each participant using a group independent component analysis. The coupling parameters reflecting the causal interactions among the DMN regions were estimated using spectral dynamic causal modeling (DCM).ResultsTwenty‐seven MDD patients and 27 healthy controls were included in the statistical analysis. Our results showed declined influences from the left parietal cortex to other DMN regions in the pre‐treatment patients as compared with healthy controls. After eight weeks of treatment, the influence from the right parietal cortex to the posterior cingulate cortex significantly decreased.ConclusionThese findings suggest that the reduced excitatory causal influence of the left parietal cortex is the key alteration of the DMN in patients with MDD, and the disrupted causal influences that parietal cortex exerts on the posterior cingulate cortex is responsive to antidepressant treatment.

Understanding the neural basis of Major Depressive Disorder (MDD) is important for the diagnosis and treatment of this mental disorder. The default mode network (DMN) is considered to be highly involved in the MDD. To find directed interaction between DMN regions associated with the development of MDD, the effective connectivity within the DMN of the MDD patients and matched healthy controls was estimated by using a recently developed spectral dynamic causal modeling. Sixteen patients with MDD and sixteen matched healthy control subjects were included in this study. While the control group underwent the resting state fMRI scan just once, all patients underwent resting state fMRI scans before and after two months' treatment. The spectral dynamic causal modeling was used to estimate directed connections between four DMN nodes. Statistical analysis on connection strengths indicated that efferent connections from the medial frontal cortex (MFC) to posterior cingulate cortex (PCC) and to right parietal cortex (RPC) were significant higher in pretreatment MDD patients than those of the control group. After two-month treatment, the efferent connections from the MFC decreased significantly, while those from the left parietal cortex (LPC) to MFC, PCC and RPC showed a significant increase. These findings suggest that the MFC may play an important role for inhibitory conditioning of the DMN, which was disrupted in MDD patients. It also indicates that disrupted suppressive function of the MFC could be effectively restored after two-month treatment.