Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
PubMed database.


METHODS
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.


METHODS
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.


RESULTS
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.
Minzenberg
Michael J
MJ
Department of Psychiatry, University of California-Davis School of Medicine, Sacramento, CA 95817, USA. michael.minzenberg@ucdmc.ucdavis.edu
Laird
Angela R
AR
Thelen
Sarah
S
Carter
Cameron S
CS
Glahn
David C
DC
D000328:Adult; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D020645:Mediodorsal Thalamic Nucleus / Q000503:physiopathology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000503:physiopathology; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*