| Background Schizophrenia is a set of complex mental disorders of unknown etiology,with clinical symptoms including hallucinations,delusions,speech or behavior disorder,and usually presents cognitive dysfunction.Auditory verbal hallucinations(AVH)are the most common core symptoms of schizophrenia.Around 25% of patients who experience AVH in schizophrenia are resistant to antipsychotic medication,and are easy to develop into chronic and refractory AVH,which seriously damages their life quality,even leading to violence behaviors such as suicide or attack.However,the pathogenesis of auditory hallucination is inadequately understood.Repetitive transcranial magnetic stimulation(r TMS)is a non-invasive brain stimulation technique that uses a rapidly varying magnetic field to induce an electrical current in selective regions to change the activities of cortical neuron.So far,more and more scholars pay attention to r TMS treatment for AVH,but the sequence parameters and target positions for different treatment are various.Clinical curative effects of the treatment are not exact,and the mechanisms of the treatment are still not clear.The development of neuroimaging and electroencephalogram techniques provides novel methods for investigating the pathogenesis of neural mental illness.Especially,the whole brain function connection strength(FCS)analysis based on the resting state functional magnetic resonance imaging(rs-f MRI)data,and the whole brain function connection analysis of electroencephalogram(EEG)can effectively describe overall properties of the whole brain networks,revealing the mechanisms of brain network.Objective By utilizing resting state f MRI and EEG methods,the brain network of schizophrenia patients with auditory hallucination can be explored.By observing the clinical efficacy for AVH patients before and after the r TMS treatment,we can understand the brain neural mechanisms for AVH in schizophrenia.(1)Enormous studies have suggested that AVH is closely related with hearing related primary cortex and the frontal cortex that control the cognitive.Base on previous studies,our researchs adopt rs-f MRI and EEG data based whole brain functional connectivity analysis method to explore the brain network bases of AVH.(2)We apply r TMS to treat auditory hallucination,to observe its clinical curative effects,analyses rs-f MRI data,explore the brain-neural-mechanisms of the r TMS for AVH.Methods(1)By acquiring resting state f MRI data of 31 schizophrenia patients with AVH,26 patients without AVH and control groups with 33 healthy people,and resting state EEG data of 27 schizophrenia patients with AVH,26 patients without AVH and control groups with 48 healthy people,and using the whole brain functional connectivity analysis method,we can learn the brain network bases of AVH.(2)Based on neuroimaging navigation and positioning technology,we employ r TMS over the left temporoparietal junction(TPJ)for patients,collect the clinical symptoms assessment of 16 patients before and after treatment and rs-f MRI of 30 healthy people,and observe the r TMS treatment effects of AVH and its neural mechanisms.Results(1)FCS values on the left cerebellum of schizophrenia patients with AVH were significantly higher than the non-AVH schizophrenia patients and healthy people.For patients(no matter AVH or non-AVH),the FCS values on right ventromedial prefrontal cortex and cerebellum were significantly lower than that of healthy people,and back in the left temporal,the FCS values for patients are significantly higher than that for healthy people.In addition,FCS values displayed great different between AVH and non-AVH patients,on the left temporoparietal junction,central sulcus,cuneus and thalamus.The EEG analyses had shown that the whole brain functional connectivity of the left middle frontal cortex and left temporoparietal junction,the left middle frontal cortex and right temporoparietal junction,the left middle frontal cortex and right posterior cingutate,the left temporoparietal junction and left anterior cingutate,the left temporoparietal junction and right anterior cingulate,the left temporoparietal junction and right middle frontal cortex,the left inferior parietal lobule and right middle frontal cortex,the right temporoparietal junction and left anterior cingulate for patients(no matter AVH or non-AVH)were significantly lower than that for healthy people.(2)The symptom and the PANSS score of AVH patients significantly reduced after r TMS treatment.FCS results indicate that after treatment,the AVH patients show significant increase of FSC values on the left inferior parietal lobule and cuneus,while on the left cerebellum,the FCS values significantly reduced.Further seed segmentation-brain analysis found that the function connection between left inferior parietal lobule and middle frontal gyrus and function connection between precuneus and cingulate cortex increased significantly,while the function connection between left cerebellum and anterior cerebellar decreased significantly.Related analysis showed that FCS values of the left cerebellum in the baseline period and the FCS value change before and after treatment are remarkably related with the auditory hallucinations rating scale(AHRS)scores and the PANSS scores.Conclusion(1)This study suggests that the whole brain function connections are abnormal in schizophrenia patients with AVH,including dysconnection of the prefrontal cortex,temporoparietal junction,left cerebellum,middle temporal gyrus and cingulate cortex.Especially,the whole brain function connection damage of the left cerebellum,might be the characteristic brain network bases of schizophrenia patients with AVH.(2)Based on the navigation technology of neuroimaging,we applicated r TMS to stimulate the left temporoparietal junction,which can significantly improve the clinical symptoms such as auditory hallucinations by adjusting dysconnection of the temporoparietal junction,cuneus and cerebellum and other brain function networks. |
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