Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

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J Psychiatry Neurosci 2012;37(6):379-88

Ans Vercammen, PhD; Richard Morris, PhD; Melissa J. Green, PhD; Rhoshel Lenroot, MD, PhD; Jayashri Kulkarni, MD, PhD; Vaughan J. Carr, MD, PhD; Cynthia Shannon Weickert, PhD; Thomas W. Weickert, PhD

Vercammen, Morris, Lenroot, C.S. Weickert, T.W. Weickert — Neuroscience Research Australia, Randwick, Australia; Vercammen, Morris, Green, Lenroot, Carr, C.S. Weickert, T.W. Weickert — School of Psychiatry, University of New South Wales, Randwick, Australia; Vercammen, Morris, Green, Carr, C.S. Weickert, T.W. Weickert — Schizophrenia Research Institute, Darlinghurst, Australia; Kulkarni — Monash Alfred Psychiatric Research Centre, Melbourne, Australia


Background: Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechan isms and emotion attribution processes in people with schizophrenia.

Methods: Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence.

Results: We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex.

Limitations: Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables.

Conclusion: Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life.

Submitted July 26, 2011; Revised Jan. 11, Feb. 20, 2012; Accepted Feb. 22, 2012.

Acknowledgements: This work was supported by the University of New South Wales School of Psychiatry, NHMRC Project Grant no. 568807, Neuroscience Research Australia and the Australian Schizophrenia Research Bank, which is supported by the National Health and Medical Research Council of Australia, the Pratt Foundation, Ramsay Health Care and the Viertal Charitable Foundation. C.S.Weickert is also supported by the Schizophrenia Research Institute, utilizing infrastructure funding from NSW Health, and funding from the Macquarie Group Foundation..

Competing interests: None declared for R. Morris, M.J. Green, R. Lenroot and V.J. Carr. As above for A. Vercammen, J. Kulkarni, C.S. Weickert and T.W. Weickert. A. Vercammen also declares having received travel support from the International Congress on Schizophrenia Research. J. Kulkarni serves on the advisory boards for Lundbeck, Janssen Cilag, Asta Zeneca and Eli Lilly; declares having received insitutional grant support from Astra Zeneca, Janssen Cilag, Eli Lilly, Amgen and Roche; has received lectures fees from Jansen Cilag, Astra Zeneca and Eli Lilly; has a patent pending with EVestG; receives royalties from Cambridge University Press; and has received payment from Medimark Australia for preparing educational material on women and schizophrenia.

Contributors: M.J. Green, R. Lenroot, C.S. Weickert and T.W.Weickert designed the study. A. Vercammen and R. Morris acquired the data. A. Vercammen, R. Morris, R. Lenroot, J. Kulkarni, V.J. Carr, C.S. Weickert and T.W. Weickert analyzed the data. A. Vercammen, C.S. Weickert and T.W. Weickert wrote the article. All authors reviewed the article and approved its publication.

DOI: 10.1503/jpn.110088

Correspondence to: A. Vercammen, Neuroscience Research Australia, Hospital Road, Randwick, NSW 2031, Australia;