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Reduced Proactive Inhibition in Schizophrenia Is Related to Corticostriatal Dysfunction and Poor Working Memory

  • Bram B. Zandbelt
    Correspondence
    Address correspondence to Bram B. Zandbelt, Ph.D., Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Room A.01.126, PO Box 85500, Utrecht, The Netherlands 3508 GA, Netherlands
    Affiliations
    Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands
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  • Mariët van Buuren
    Affiliations
    Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands
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  • René S. Kahn
    Affiliations
    Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands
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  • Matthijs Vink
    Affiliations
    Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands
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Published:September 09, 2011DOI:https://doi.org/10.1016/j.biopsych.2011.07.028

      Background

      Inhibitory control is central to executive functioning and appears deficient in schizophrenia. However, it is unclear how inhibitory control is affected, what the underlying neural mechanisms are, whether these deficits are related to the illness itself or to increased risk for the illness, and whether there is a relation to impairments in other executive functions.

      Methods

      We used functional magnetic resonance imaging to investigate two forms of inhibitory control: proactive inhibition (anticipation of stopping) and reactive inhibition (outright stopping). Twenty-four schizophrenia patients, 24 unaffected siblings, and 24 healthy control subjects performed a modified version of the stop-signal paradigm. To assess the relation between performance on inhibitory control and other executive functions, we correlated inhibitory control indices with working memory span.

      Results

      Compared with control subjects, proactive inhibition was reduced in patients and siblings. Reactive inhibition was unaffected. Reduced proactive inhibition was associated with a failure to activate the right striatum, the right inferior frontal cortex, and the left and right temporoparietal junction. Activation during reactive inhibition was unaffected. Those patients with the least proactive inhibition also showed the shortest working memory span.

      Conclusions

      These results suggest that schizophrenia is associated with reduced proactive inhibition, probably resulting from corticostriatal dysfunction. This deficit is related to an increased risk for schizophrenia and likely reflects a general executive function deficit rather than a specific inhibitory control impairment.

      Key Words

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      Linked Article

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        Biological PsychiatryVol. 70Issue 12
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