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Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI

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Abstract

Rationale and objective

In animal and human studies, the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) has been implicated in mediating impulsiveness and aggression. To test the hypothesis that 5-HT modulates neuro-cognitive brain activation during inhibitory control, we examined the effect of acute tryptophan depletion (ATD), a dietary challenge, which has been shown to decrease 5-HT synthesis in the brain, on functional brain activation during a go/no-go task.

Methods

Nine healthy, right-handed volunteers performed a rapid, event-related go/no-go task in two functional magnetic resonance imaging (fMRI) scanning sessions, 5 h after either a tryptophan-free or a balanced amino acid drink in a double-blind, sham depletion-controlled, counterbalanced, crossover design. The task required subjects to selectively execute or inhibit a motor response. Tryptophan depletion significantly lowered total plasma tryptophan concentration by 80%, but did not significantly alter inhibitory performance or mood ratings.

Results

ATD significantly reduced right orbito-inferior prefrontal activation during the no-go condition, and increased activation in superior and medial temporal cortices.

Conclusions

These findings provide neuro-functional evidence of a serotonergic modulation of right inferior prefrontal during inhibitory motor control. The increased engagement of temporal brain regions may reflect compensatory mechanisms.

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Acknowledgements

We are grateful to Dr. Kate John in the Department of Clinical Biochemistry for the analysis of the tryptophan assays. The study was funded by the Theodore and Vada Stanley Foundation.

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

    Katya Rubia, Francis Lee, Anthony J. Cleare, Nigel Tunstall, Cynthia H. Y. Fu, Michael Brammer & Phillip McGuire

  2. Department of Psychiatry, Institute of Psychiatry, 16 De Crespigny Park, London, SE5 8AF, UK

    Katya Rubia

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  1. Katya Rubia
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  2. Francis Lee
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Correspondence to Katya Rubia.

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Rubia, K., Lee, F., Cleare, A.J. et al. Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI. Psychopharmacology 179, 791–803 (2005). https://doi.org/10.1007/s00213-004-2116-z

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