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Effects of ketamine on prefrontal and striatal regions in an overt verbal fluency task: a functional magnetic resonance imaging study

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Abstract

Rationale

Glutamatergic dysfunction at N-methyl-d-aspartate (NMDA) receptors has been proposed as a neurochemical model for schizophrenia. A key feature of this disorder is impairments in cognitive function.

Objective

The present study sought to investigate the effects of ketamine, an NMDA antagonist, on the performance and neural correlates of verbal fluency, a task that engages executive function.

Methods

Ten healthy dextral male volunteers received intravenous placebo normal saline or ketamine (bolus of 0.23 mg/kg and infusion of 0.65 mg/kg), administered in a double-blind, randomized order, during two functional magnetic resonance imaging sessions. During scanning, subjects performed a verbal fluency task. Two levels of cognitive load were examined in the task, and overt responses were acquired in order to measure subject performance on-line.

Results

Ketamine induced symptoms in the healthy individuals comparable to an acute psychotic state. Although ketamine did not significantly impair task performance relative to placebo, an interaction of task demand with ketamine was observed in the anterior cingulate, prefrontal, and striatal regions.

Conclusions

The behavioural and functional effects of ketamine during verbal fluency in healthy individuals were comparable to those evident in patients with schizophrenia. The findings support a role for glutamatergic dysfunction in the pathophysiology of schizophrenia.

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Acknowledgements

This work was supported by a Wellcome Trust Fellowship to CF and from the Mason Medical Foundation to KMA. We would also like to thank the radiographers at the MRI Center, Maudsley and South London NHS Trust, for their expert assistance. The experiments in the present study comply with the current laws of the UK, in which they were performed.

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Authors and Affiliations

  1. Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK

    Cynthia H. Y. Fu, Matthew P. G. Allin, David Gasston, Sergi G. Costafreda, Steve C. R. Williams & Philip K. McGuire

  2. Department of Psychiatry and Behavioural Sciences, Manchester University, Williamson Building, Manchester, M13 9PL, UK

    Kathryn M. Abel

  3. Brain Mapping Unit, Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, UK

    John Suckling

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  1. Cynthia H. Y. Fu
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  2. Kathryn M. Abel
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  4. David Gasston
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Correspondence to Cynthia H. Y. Fu.

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Fu, C.H.Y., Abel, K.M., Allin, M.P.G. et al. Effects of ketamine on prefrontal and striatal regions in an overt verbal fluency task: a functional magnetic resonance imaging study. Psychopharmacology 183, 92–102 (2005). https://doi.org/10.1007/s00213-005-0154-9

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