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Midbrain presynaptic dopamine tone predicts sustained and transient neural response to emotional salience in humans: fMRI, MEG and FDOPA PET

Molecular Psychiatry volume 18, pages 4–6 (2013)Cite this article

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The midbrain dopamine system is implicated in mediating the reactivity of the organism to salient environmental stimuli,1, 2 including emotional events,3 at different timescales.2 Preclinical and human neuroimaging studies implicate the dopamine system in coding stimulus salience4 through its innervations of nigrostriatal and mesocorticolimbic pathways,1, 2 and dysfunction of this system has an important role in neuropsychiatric disorders such as schizophrenia and depression that are accompanied by impaired social and emotional cognition. However, the role of dopamine in modulating transient (in milliseconds) distributed neural representation of human emotional cognition remains undefined. We examined the relationship of midbrain presynaptic dopamine (directly measured with positron emission tomography (PET)) to ‘sustained’ and ‘transient’ neural responses to salient emotional facial expressions (measured with fMRI and magnetoencephalography (MEG), respectively).

A total of 21 healthy participants (mean age=31, six females) consented according to NIH-IRB and Radiation Safety Committee guidelines before undergoing 90 min PET scans following IV administration of 16-mCi[18F]fluoroDOPA (FDOPA). A cerebellar reference region was used to determine FDOPA-Ki, a reproducible measure of presynaptic DA stores and synthesis.5 After coregistration of FDOPA scans onto native space MRIs, a manually-defined midbrain volume of interest within each individual's MRI was used for extraction of mean Ki values (Supplementary Information).

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Acknowledgements

We thank our colleagues at the NMR centre, MEG core facility and PET department for their technical support. We also thank Drs Christian van der Gaag and Christian Keysers for access to the video stimuli and Drs Caroline F Zink and Alex Martin for helpful comments. This work is supported by the intramural research program of the National Institute Of Mental Health.

Author contributions

MJ conceived and designed the experiments and wrote the manuscript. TN, MJ, PK, AI, DR, JSK, TH, FWC and JCM performed the experiments and analyzed the data; PK and SER contributed analytical tools and PK performed video timecourse analysis. RC and KFB supervised all the aspects of this project. All authors contributed to the manuscript.

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Authors and Affiliations

  1. Section on Integrative Neuroimaging, Bethesda, MD, USA

    M Jabbi, T Nash, P Kohn, A Ianni, D Rubinstein, J C Masdeu, J Shane Kippenhan & K F Berman

  2. Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, Bethesda, MD, USA

    M Jabbi, T Nash, P Kohn, A Ianni, D Rubinstein, J C Masdeu, J Shane Kippenhan, R Coppola & K F Berman

  3. Magnetoencephalography Core Facility,

    D Rubinstein, T Holroyd, F W Carver, S E Robinson & R Coppola

  4. National Institute of Mental Health, National Institutes of Health, Intramural Research Program, Bethesda, MD, USA

    D Rubinstein, T Holroyd, F W Carver, S E Robinson & R Coppola

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  1. M Jabbi
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  2. T Nash
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Corresponding author

Correspondence to M Jabbi.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Jabbi, M., Nash, T., Kohn, P. et al. Midbrain presynaptic dopamine tone predicts sustained and transient neural response to emotional salience in humans: fMRI, MEG and FDOPA PET. Mol Psychiatry 18, 4–6 (2013). https://doi.org/10.1038/mp.2012.12

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