Diminished language lateralization in schizophrenia corresponds to impaired inter-hemispheric functional connectivity

Introduction: A consistent brain imaging finding in schizophrenia is decreased language-asymmetry, already evident in first episode patients, thus arguing for a biomarker of the disorder. Nonetheless, its specificity to schizophrenia is questionable. Furthermore, while previous studies suggested that enhanced right hemisphere activation underlies this diminished asymmetry, the mechanism for this anomaly is yet unknown. This study aimed to examine the role of inter-hemispheric relations in such abnormality through functional connectivity analysis driven by left inferior frontal gyrus (IFG) activation. To test for disorder specificity we compared schizophrenia patients not only to healthy controls but also to patients with obsessive compulsive disorder (OCD). Methods: Functional magnetic resonance imaging (fMRI) was applied during an auditory verb generation task in the 3 groups. Language-related activation in BA44/45 located in the IFG was used for regional estimation of brain asymmetry and for assessment of inter-hemispheric functional connectivity. Results: Schizophrenia, but not OCD patients showed reduced language asymmetry in the IFG relative to healthy controls and diminished functional connectivity between the left and right IFG. Importantly, decreased inter-hemispheric functional connectivity in the IFG was related to more negative symptoms among the schizophrenia patients. Conclusions: Diminished language-related asymmetry in the IFG seems to be an early disorder specific neural marker of schizophrenia, supporting its pathogenic role. The relation of this regional abnormality to reduced inter-hemispheric functional connectivity and symptom severity supports the role of large-scale brain disorganization in schizophrenia. This may relate to the known structural abnormalities of the corpus callosum leading to functional hemispheric dysconnection.