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Michael J. Minzenberg, MD; Angela R. Laird, PhD; Sarah Thelen, BS; Cameron S. Carter, MD; David C. Glahn, PhD

Arch Gen Psychiatry. 2009;66(8):811-822.

Context  Prefrontal cortical dysfunction is frequently reported in schizophrenia. It remains unclear whether this represents the coincidence of several prefrontal region- and process-specific impairments or a more unitary dysfunction in a superordinate cognitive control network. Whether these impairments are properly considered reflective of hypofrontality vs hyperfrontality remains unresolved.

Objectives  To test whether common nodes of the cognitive control network exhibit altered activity across functional neuroimaging studies of executive cognition in schizophrenia and to evaluate the direction of these effects.

Data Sources  PubMed database.

Study Selection  Forty-one English-language, peer-reviewed articles published prior to February 2007 were included. All reports used functional neuroimaging during executive function performance by adult patients with schizophrenia and reported whole-brain analyses in standard stereotactic space. Tasks primarily included the delayed match-to-sample, N-back, AX-CPT, and Stroop tasks.

Data Extraction  Activation likelihood estimation modeling reported activation maxima as the center of a 3-dimensional gaussian function in the meta-analysis, with statistical thresholding and correction for multiple comparisons.

Data Synthesis  In within-group analyses, healthy controls and patients activated a similarly distributed cortical-subcortical network, prominently including the dorsolateral prefrontal cortex (PFC), ventrolateral PFC, anterior cingulate cortex (ACC), and thalamus. In between-group analyses, patients showed reduced activation in the left dorsolateral PFC, rostral/dorsal ACC, left thalamus (with significant co-occurrence of these areas), and inferior/posterior cortical areas. Increased activation was observed in several midline cortical areas. Activation within groups varied modestly by task.

Conclusions  Healthy adults and schizophrenic patients activate a qualitatively similar neural network during executive task performance, consistent with the engagement of a general-purpose cognitive control network, with critical nodes in the dorsolateral PFC and ACC. Nevertheless, patients with schizophrenia show altered activity with deficits in the dorsolateral PFC, ACC, and mediodorsal nucleus of the thalamus. Increases in activity are evident in other PFC areas, which could be compensatory in nature.

Author Affiliations: Department of Psychiatry, University of California–Davis School of Medicine, Sacramento (Drs Minzenberg and Carter); Research Imaging Center, University of Texas Health Science Center at San Antonio, San Antonio (Dr Laird and Ms Thelen); and Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut (Dr Glahn).

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