Language Lateralization In Schizophrenia:Exploring The Gene,Brain,and Behavior Relationships

The functional lateralization of the cerebral hemispheres is one of the organizing principles of the brain,which reflects the functional differences between the left and right hemispheres.Most of the right-handed healthy individuals show complementary specialization of hemispheres.The left hemisphere has the advantage of language and the right hemisphere has the advantage of visual spatial function.In patients with schizophrenia,it is generally found that the degree of left lateralization of language is reduced.On the one hand,as a disease associated with abnormal brain networks,the relationship between reduced language lateralization and the structural and functional networks in schizophrenia is not clear.On the other hand,as a genetic disease,the relationship between schizophrenia-related genes and language lateralization is also not clear.This study investigated patients with schizophrenia using multimodal MRI and genetic data at multiple levels,starting from the core language brain area,upwards to the function and structural brain network level,and downwards to the gene level that ultimately affects function,to explore the relationship between schizophrenia’s brain structural and functional network and language lateralization,as well as the influence of genes.Specifically,the study addressed the following questions:1)Are the changes in functional lateralization of patients with schizophrenia limited to language function?2)Does the altered lateralization pattern of patients with schizophrenia conform to the Causal hypothesis of hemisphere complementarity?3)Is the abnormality of language lateralization in patients with schizophrenia related to changes in the function and structural network of the brain?4)What is the relationship between schizophrenia,language lateralization,and genes?Regarding question 1,Study 1 found that in patients with schizophrenia,both the language production function and the visual spatial function showed a pattern of reduced degree of lateralization.which indicates that the abnormal lateralization of brain function in schizophrenia may be general.Regarding question 2,Study 1 found that as an atypical group of lateralization,there was a significant negative correlation between the lateralization of language and visual spatial function in schizophrenia group,indicating that the lateralization pattern conforms to the Causal hypothesis about the complementary specialization.Regarding question 3,Study 2 found that patients with schizophrenia with a higher degree of left-lateralization showed a closer connection between the left pars opercularis and the contralateral mirror area as well as the left pars opercularis to the bilateral thalamus.In terms of functional network characteristics,such patients were more inclined to local functional differentiation rather than whole brain functional integration.Study 3 further found that the relationship between language lateralization and the cortexthalamus in schizophrenia had structural foundation:the more left-lateralized the language function,the weaker the ability to communicate information in the right pars opercularis and the structural network,and the sparser the connections between hubs.Regarding question 4,Study 4 found that the haplotype of FOXP2 gene carrying TATT and the haplotype of SLC1A1 not carrying GC were the main genetic factors of schizophrenia.The results of multivariate logistic analysis suggested the reduced language lateralization as an additional factor that increased the disease possibility.Based on the above four studies,this paper showed that in addition to language functions,there is a reduction in visual spatial function lateralization in schizophrenia;the reduction in language lateralization is related to changes in the topological characteristics of structural and functional networks;Decreased language lateralization may increase the risk of schizophrenia as a factor other than genes.These findings provide new evidence for understanding the relationship between schizophrenia and functional lateralization and its biological foundation.