Functional Connectivity Characteristics Of Amygdala And Its Subregions Related Pathways And Their Clinicopathological Significance In Schizophrenia

Objective:Neuroimaging studies demonstrated that the abnormalities of amygdala may be implicated in schizophrenia neuronal pathophysiology.The aim of this study:1.To investigate the functional connectivity(FC)characteristics of amygdala-centered primary emotional perception pathway and high emotional control pathway in first-episode schizophrenia(FES)during resting-state,and their mechanisms in the occurrence of clinical symptoms.2.Based on the structural and functional heterogeneity of the amygdala,we further investigate the resting-state FC patterns of the above two pathways centered on amygdala subregions in FES,and their respective correlation with core clinical symptoms.Methods:The present study used a cross-sectional and longitudinal follow-up study design.Schizophrenia patients were enrolled according to the diagnostic criteria of the tenth revision of the International Statistical Classification of Diseases and Related Health Problems(ICD-10),and their clinical symptoms and social cognitive function were also evaluated by the Positive and Negative Syndrome Scale(PANSS)and the Mayer-Salovery-Calovery Emotional Intelligence Test-Managing Emotion(MSCEIT-ME).All participants underwent resting-state multiband functional magnetic resonance imaging.Participants included 77 FES patients and 77 age-,sex-,education-matched healthy controls(HC)at baseline,and 34 FES patients at 8-week follow-up.In the resting state,the following two parts were discussed respectively based on regions of interest(ROIs)FC analysis:1.Study 1:①At baseline,the differences in FC of amygdala-centered primary emotional perception pathway and high emotional control pathway between FES patients and HC were analyzed,and the relationship between abnormal FC and clinical symptoms of patients were explored;②Longitudinal data were used to conduct the altered FC of the amygdala related pathways in patients with FES,then a correlation analysis between the dynamic changes of FC and the improvement of clinical symptoms was further performed.2.Study 2:①At baseline,the differential FC patterns of primary emotional perception pathway and high emotional control pathway centered on amygdala subregions including centromedial(CMA),basolateral(BLA)and superficial amygdala(SFA)between the two groups were analyzed,and the correlation analyses between the FC values of brain regions with significant between-group differences and clinical symptoms were carried out in FES patients;②Follow-up analyses were done to examine the alterations of FC of the amygdala subregions related pathways in patients with FES,and to further analyze the dynamic changes of FC and clinical improvement.Results:1.Significantly different FC of amygdala-centered primary emotional perception pathway and high emotional control pathway was observed in the FES group compared with the HC group.Notably,the amygdala-lateral orbitofrontal cortex(lOFC)connectivity was negatively correlated with negative symptoms in patients with FES at baseline(p<0.05).2.After 8 weeks of treatment,the FC patterns of amygdala-centered primary emotional perception pathway and high emotional control pathway were partially changed in the patients group.And the change of the former correlated with the change of negative symptom score,while the change of the latter was mainly related to the change of emotional management score and the positive symptom score(p<0.05).3.Among the 6 subregions of amygdala,only the left CMA-,bilateral BLA-,and bilateral SFA-centered primary emotional perception pathway and bilateral high emotional control pathway exhibited abnormal FC in FES patients.Besides,the SFA/the left BLAlateral orbitofrontal connectivity was negatively correlated with the negative symptoms in patients with FES.4.After 8 weeks of treatment,only the FC pattern of the right SFA-centered high emotional control pathway was significantly changed,mainly manifested as the decreased FC of right SFA and the caudal anterior cingulate cortex(cACC).And the change of FC was associated with the change of the emotional management score and positive symptom score(p<0.05).Conclusion:1.The present findings demonstrate local abnormal FC patterns of the amygdala-centered primary emotional perception pathway and high emotional control pathway in FES patients,and the function of local brain circuit may be partially relieved after 8 weeks of treatment.The decreased amygdala-IOFC network in the primary emotional perception pathway may lead to the weakening of the ability to perceive social emotional information from bottom to top,and then contribute to negative symptoms such as emotional retardation and emotional withdrawal in schizophrenia.The abnormal functional connectivity of DLPFC/cACC-amygdala in high emotional control pathway may be one of the neural mechanisms of social cognitive deficits and positive symptoms.2.The selective FC abnormalities in the primary emotional perception pathway and bilateral SFA-centered high emotional control pathway were observed in FES patients.Furthermore,as part of the brain circuits reflecting the amygdala-lOFC network,the decreased BLA/SFA-lOFC connectivity associated with the occurrence of negative symptoms in FES patients.The abnormal functional connectivity of cACC-SFA in high emotional control pathway may be one of the neural mechanisms of social cognitive deficits and positive symptoms in schizophrenia.