Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance

Background: Working memory (WM) deficits in schizophrenia have been associa ted with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic v ersus normal subjects during WM performance (Manoach et al 1999b), We now h ave investigated whether schizophrenic subjects recruit different brain reg ions, particularly the basal ganglia and thalamus, components of frontostri atal circuitry thought to mediate WM. Methods: We examined regional brain activition in nine normal and nine schi zophrenic subjects during WM performance using functional magnetic resonanc e imaging. Subjects performed a modified version of the Sternberg Item Reco gnition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM base line condition. We examined activation in both individual subjects and aver aged group data. Results: Relative to normal subjects, schizophrenic subjects exhibited defi cient WM performance, at least an equal magnitude of right DLPFC activation , significantly greater left DLPFC activation and increased spatial heterog eneity of DLPFC activation. Furthermore, only the schizophrenic group activ ated the basal ganglia and thalamus, even when matched for task performance with the normal group. Conclusions: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM, Futu re studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits. Biol Psychiatry 2000;48: 99-109 (C) 2000 Soc iety of Biological Psychiatry.