Multimodal Magnetic Resonance Imaging Study In Schizophrenia Patients With Persistent Auditory Verbal Hallucination

Objective:Schizophrenia is a chronic,severe,and disabling mental disorder,with a high disabling rate of 80%.It seriously affects patients’ quality of life and causes economic and social burdens.Auditory verbal hallucination(AVH)is one of the hallmark positive symptoms of schizophrenia,affecting 60%-80% of patients with schizophrenia.However,the neuroimaging mechanisms of AVH,especially persistent AVH(p AVH),are still unclear.To explore the brain imaging mechanisms underlying the development of p AVH in schizophrenia patients,this study used multimodal magnetic resonance imaging to compare the characteristics of changes in cortical thickness,fractional amplitude of low frequency fluctuations(f ALFF),and proton resonance spectra in schizophrenia patients with p AVH(p AVH groups),schizophrenia patients without AVH(non-AVH groups),and healthy controls(HC groups).Methods:(1)Patients who met the DSM-5 diagnostic criteria for schizophrenia were divided into p AVH groups(P3 score ≥ 4)and non-AVH groups(P3 score = 1)according to the P3 item of the Positive and Negative Syndrome Scale(PANSS).79 schizophrenia patients with p AVH,60 schizophrenia patients without AVH,and 83 healthy controls were recruited for this study.A self-administered general information questionnaire was used to collect general demographic information on the subjects.The PANSS scale was used to assess the severity of the patients’ psychiatric symptoms.The P3 item of the PANSS scale and Auditory Hallucinations Rating Scale(AHRS)were used to assess the severity of AVH.MATRICS Consensus Cognitive Battery(MCCB)was used to assess subjects’ neurocognitive function.Surface-based morphology(SBM)analysis was performed to compare differences in cortical thickness between the three groups of subjects,and correlation analysis was performed to explore the relationship between cortical thickness in the differential brain regions of patients and the severity of clinical symptoms.(2)The f ALFF of 64 from p AVH groups,39 from non-AVH groups,and 60 healthy controls were analyzed using resting-state f MRI data to investigate the local spontaneous neural activity in the brain of the three groups of subjects and their relationship with the severity of clinical symptoms.(3)Based on the region of interest medial prefrontal cortex(m PFC)approach,proton resonance spectroscopy data were collected and analyzed in 61 schizophrenia patients with p AVH,53 schizophrenia patients without AVH and 59 healthy controls to explore the differences in metabolite levels in the m PFC of the three groups of subjects and their relationship with the severity of clinical symptoms.Results:(1)The cortical thickness of the bilateral lateral orbitofrontal cortex was significantly lower in p AVH groups than in non-AVH groups and HC groups.It was significantly negatively correlated with the severity of p AVH.No differences were found between non-AVH groups and HC groups.In addition,there were no differences in other brain regions in p AVH groups compared with non-AVH and HC groups.(2)The f ALFF values of the right lingual gyrus,right postcentral gyrus,and left supplementary motor area in p AVH group were lower than those in HC group,while the f ALFF values of right medial superior frontal gyrus,left inferior parietal lobule,left precuneus,and right supramarginal gyrus was higher than those in HC group.The f ALFF values in the left lingual gyrus,right postcentral gyrus,and left supplementary motor area in the non-AVH group were lower than that in the HC group,but only the f ALFF value in the right medial superior frontal gyrus was higher than that in the HC group.However,there was no difference in f ALFF values between the p AVH group and non-AVH groups.(3)The metabolic levels of t NAA and Glx in m PFC of p AVH groups were both lower than those of non-AVH and HC groups and were both negatively correlated with the severity of p AVH.In contrast,no significant differences were found between non-AVH and HC groups.(4)In the above three sub-studies,four dimensions of neurocognitive function in p AVH group including Hopkins Verbal Learning Test-Revised(HVLT-R),Continuous Performance Test(CPT),Trail Making Test A and B(TMTA and TMTB),and Stroop Color and Word Test(SCWT)were significantly worse than HC group.Correlation analysis showed that there was no correlation between brain imaging indexes and cognitive function in schizophrenia patients with p AVH.Conclusions:(1)In the analysis of brain structure,the cortical thickness of the bilateral lateral orbitofrontal cortex was significantly lower in p AVH groups than in non-AVH and HC groups,and was significantly negatively correlated with the severity of p AVH.These results suggest that anatomical defects in the frontal cortex,especially in the bilateral lateral orbitofrontal cortex,may be associated with the pathogenesis of phantom hearing in schizophrenia patients.(2)In the analysis of brain function,the brain region with decreasing f ALFF values in the p AVH group and non-AVH group were the same.In addition to the medial frontal cortex,several brain regions of the parietal cortex were included in the p AVH groups compared with non-AVH group.These results suggest that schizophrenia patients with p AVH have more extensive damage to the local autonomic neural activity in the brain,and the change of autonomic neural activity in these brain regions may provide some value for the treatment of AVH.(3)In the analysis of proton magnetic resonance spectroscopy,the metabolic levels of t NAA and Glx in the m PFC of schizophrenia patients with p AVH were lower than those of schizophrenia patients without AVH and healthy controls.They were both negatively correlated with the severity of p AVH.These results suggest that the reduced metabolic levels of t NAA and Glx in the m PFC of schizophrenia patients with p AVH may be related to the severity of p AVH and that improving the metabolic levels of t NAA and Glx in the m PFC of schizophrenia patients with p AVH may be a potential therapeutic target for p AVH.(4)In the above three sub-studies,schizophrenia patients with p AVH have obvious functional defects in various dimensions of neurocognition including the ability to learn and remember the speech,attention maintenance,the speed of information processing,and the ability to inhibit executive functions.Unfortunately,all three studies showed no correlation between brain imaging indicators and cognitive function in patients with schizophrenia with p AVH.