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Schizophrenia (SCZ), as a chronic and persistent disorder, exhibits workingmemory deficits across various stages of the disorder, yet the neuralmechanisms underlying these deficits remain elusive with inconsistentneuroimaging findings. We aimed to compare the brain functional changes ofworking memory in patients at different stages: clinical high risk (CHR),first-episode psychosis (FEP), and long-term SCZ, using meta-analyses offunctional magnetic resonance imaging (fMRI) studies. Following a systematicliterature search, fifty-six whole-brain task-based fMRI studies (15 for CHR,16 for FEP, 25 for long-term SCZ) were included. The separate and pooledneurofunctional mechanisms among CHR, FEP and long-term SCZ were generated bySeed-based d Mapping toolbox. The CHR and FEP groups exhibited overlappinghypoactivation in the right inferior parietal lobule, right middle frontalgyrus, and left superior parietal lobule, indicating key lesion sites in theearly phase of SCZ. Individuals with FEP showed lower activation in leftinferior parietal lobule than those with long-term SCZ, reflecting a possiblerecovery process or more neural inefficiency. We concluded that SCZ representas a continuum in the early stage of illness progression, while the neuralbases are inversely changed with the development of illness course to long-termcourse.

Neural Dysfunction Underlying Working Memory Processing at Different Stages of the Illness Course in Schizophrenia:A Comparative Meta-analysis