Working memory (WM) impairments occur across psychosis stages, 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), first-episode psychosis (early psychosis), and chronic schizophrenia (chronic psychosis). PubMed, Ovid, and Web of Science were searched up to February 2026 for functional magnetic resonance imaging (fMRI) studies comparing individuals in each stage and controls during WM. Statistical maps were requested from study authors. Seed-based d-mapping assessed WM-related fMRI correlates at each stage. Significance was set at family-wise error-corrected p<.05. Sixty-three studies were included, resulting in 68 datasets: 14 (1 map) in the at-risk stage, 9 (1 map) in the early psychosis and 45 (12 maps) in the chronic psychosis stage. In the at-risk stage, hyperactivations were found in the superior temporal gyri, right insula and putamen. At the early psychosis stage, lower activation relative to controls was identified temporo-parietal regions, prefrontal cortex, striatum and thalamus. In chronic psychosis, higher activation relative to controls was observed in the medial prefrontal cortex, anterior cingulate, superior temporal gyri, right insula, posterior cingulate, and superior frontal gyrus, whereas lower activation was found in the cerebellum, bilateral precuneus and supplementary motor area. In combined early and chronic psychosis, anterior cingulate activation was positively associated with antipsychotic dose and illness duration. Overlaps in temporo-parietal hypoactivation in the early and chronic psychosis stages were found. These findings indicate that disruptions in WM circuitry may represent a potential biomarker of psychosis staging. • This study revealed psychosis stage-specific neural correlates of working memory. • Brain activity alterations were most widespread in the chronic stage of psychosis. • Findings in the at-risk stage were the least robust. • Antipsychotic dose and illness duration correlated with anterior cingulate activity.
Avram et al. (Wed,) studied this question.