Functional brain abnormalities of cognitive impairments in schizophrenia indicating higher integration of working...

Brain functional alterations associated with overall cognitive impairments and specific cognitive domains defined by MATRICS Consensus Cognitive Battery (MCCB) and the similarities among them remain unclear in schizophrenia. Comprehensive literature review and meta-analyses of cognitive task fMRI studies were conducted to identify whole-brain differences between schizophrenia patients and healthy controls, and subgroup analyses were also conducted for each MCCB domain. Identified brain regions were mapped onto canonical brain networks. The similarity analyses between network dysfunction obtained for paired subgroup analyses with and without each MCCB domain, and between each MCCB domain and primary analysis, were calculated after controlling for sample size. Meta-regression analyses were conducted between brain alterations and demographic and clinical characteristics. The present meta-analysis encompassed 232 datasets with 5229 schizophrenia patients and 6132 healthy controls. In primary analysis, schizophrenia patients showed significant brain dysfunctions mainly within default mode and subcortical networks. Distinct brain dysfunctions for each MCCB domain were also identified. Sample size-weighted similarity analyses revealed that network alterations associated with working memory deficits, among the seven, showed the greatest convergence with brain changes identified in subgroup analysis without this domain and primary analysis (sample size-weighted Dice coefficients = 0.24 and 0.51). Significant correlations were identified between significant brain alterations and negative symptoms and years of education. Aberrant activations in default mode and subcortical networks in working memory domain showed higher similarity than those observed in the other six cognitive domains, indicating functional integration of working memory and functional specialization of remaining cognitive domains in schizophrenia.