Abnormal Effective Connectivity in the Brain is Involved in Auditory Verbal Hallucinations in Schizophrenia


Baojuan Li;Long-Biao Cui;Yi-Bin Xi;Karl J. Friston;Fan Guo;Hua-Ning Wang;Lin-Chuan Zhang;Yuan-Han Bai;Qing-Rong Tan;Hong Yin;Hongbing Lu;School of Biomedical Engineering,Fourth Military Medical University;Department of Radiology,Xijing Hospital,Fourth Military Medical University;Wellcome Trust Center for Neuroimaging,Institute of Neurology,University College London;Department of Psychiatry,Xijing Hospital,Fourth Military Medical University;


School of Biomedical Engineering, Fourth Military Medical University;Department of Radiology, Xijing Hospital, Fourth Military Medical University;Wellcome Trust Center for Neuroimaging, Institute of Neurology, University College London;Department of Psychiatry, Xijing Hospital, Fourth Military Medical University;


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(s DCM) 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-na?¨ve 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. s DCM revealed an increasedsensitivity 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 AVHspecific 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.


Effective connectivity;;Stochastic dynamic causal modeling;;Auditory verbal hallucinations;;Schizophrenia


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  • [1] Mingli Li;Tao Li;The Mental Health Center and the Psychiatric Laboratory;State Key Laboratory of Biotherapy, West China Hospital,Sichuan University;, Altered topological properties in the heritable schizophrenic brain, Neuroscience Bulletin,
  • [2] Shun Qi;Yun-Feng Mu;Long-Biao Cui;Rong Li;Mei Shi;Ying Liu;Jun-Qing Xu;Jian Zhang;Jian Yang;Hong Yin;Department of Radiology, Xijing Hospital, Fourth Military Medical University;Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University;Department of Radiotherapy, Xijing Hospital, Fourth Military Medical University;Department of Ophthalmology, The Affiliated Hospital of Xi’an Medical University;Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University;, Association of Optic Radiation Integrity with Cortical Thickness in Children with Anisometropic Amblyopia, Neuroscience Bulletin,
  • [3] M. Gavrilescu;;S. Rossell;;G. W. Stuart;;T. L. Shea;;H. Innes-Brown;;K. Henshall;;C. McKay;;A. A. Sergejew;;D. Copolov;;G. F. Egan, Reduced connectivity of the auditory cortex in patients with auditory hallucinations: a resting state functional magnetic resonance imaging study, Psychological Medicine,
  • [4] K.J. Friston;;L. Harrison;;W. Penny, Dynamic causal modelling, Neuroimage,


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