Meta-analysis of structural and functional brain abnormalities in schizophrenia with persistent negative symptoms using activation likelihood estimation

Background: Persistent negative symptoms (PNS) include both primary and secondary negative symptoms that persist after adequate treatment, and represent an unmet therapeutic need. Published magnetic resonance imaging (MRI) evidence of structural and resting-state functional brain abnormalities in schizophrenia with PNS has been inconsistent. Thus, the purpose of this meta-analysis is to identify abnormalities in structural and functional brain regions in patients with PNS compared to healthy controls. Methods: We systematically searched PubMed, Web of Science, and Embase for structural and functional imaging studies based on five research methods, including voxel-based morphometry (VBM), diffusion tensor imaging (DTI), functional connectivity (FC), the amplitude of low-frequency fluctuation or fractional amplitude of low-frequency fluctuation (ALFF/fALFF), and regional homogeneity (ReHo). Afterward, we conducted a coordinate-based meta-analysis by using the activation likelihood estimation algorithm. Results: Twenty-five structural MRI studies and thirty-two functional MRI studies were included in the meta-analyses. Our analysis revealed the presence of structural alterations in patients with PNS in some brain regions including the bilateral insula, medial frontal gyrus, anterior cingulate gyrus, left amygdala, superior temporal gyrus, inferior frontal gyrus, cingulate gyrus and middle temporal gyrus, as well as functional differences in some brain regions including the bilateral precuneus, thalamus, left lentiform nucleus, posterior cingulate gyrus, medial frontal gyrus, and superior frontal gyrus. Conclusion: Our study suggests that structural brain abnormalities are consistently located in the prefrontal, temporal, limbic and subcortical regions, and functional alterations are concentrated in the thalamo-cortical circuits and the default mode network (DMN). This study provides new insights for targeted treatment and intervention to delay further progression of negative symptoms.