Neurofunctional correlates of Working Memory across Psychosis Stages: A Systematic Review and Meta-analysis

Working memory (WM) impairments have been reported in different stages of psychosis but whether their neural correlates are shared or stage-specific is unknown. This meta-analysis examined WM-related brain activity across psychosis stages: familial and clinical high-risk for psychosis (at-risk stage), first-episode psychosis (early psychosis stage), and chronic schizophrenia (chronic psychosis stage). PubMed, Ovid, and Web of Science were searched up to July 2025 for functional magnetic resonance imaging (fMRI) studies comparing individuals in each stage and healthy controls during WM. Seed-based d-mapping assessed WM-related fMRI correlates at each stage. Significance was set at family-wise error-corrected p<.05. Forty-two studies were included: 7 in the at-risk stage, 5 in the early psychosis stage, and 30 in the chronic psychosis stage. In chronic psychosis, higher activation relative to controls was observed in the medial prefrontal cortex, rostral anterior cingulate, right insula and superior temporal gyrus, posterior cingulate cortex, left superior temporal and supramarginal gyri. Lower activation in chronic psychosis vs controls was found in the cerebellum, bilateral precuneus, middle temporal gyrus, and thalamus. The early psychosis stage was characterised by lower activation compared to controls in the dorsal anterior cingulate, bilateral caudate nuclei, and inferior frontal gyrus. No significant clusters emerged in the at-risk stage, or across stages. In combined early and chronic psychosis analyses, anterior cingulate cortex activation was positively associated with both antipsychotic dose and illness duration. These findings indicate that disruptions in WM circuitry may evolve after illness onset and may represent a potential biomarker of psychosis staging. HighlightsO_LIThis study revealed distinct brain activity patterns in early and chronic psychosis stages. C_LIO_LIAlterations in brain activity were more widespread in the chronic stage of psychosis. C_LIO_LIAntipsychotic dose and illness duration predicted anterior cingulate cortex activation. C_LIO_LIDistinct neural correlates of working memory may reflect illness progression. C_LI