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Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making

Nature Neuroscience volume 15, pages 776785 (2012) | Download Citation

Abstract

The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

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Acknowledgements

We thank S. Amemori and M. Cantor for their help with animal training and surgical procedures, P. Tierney, H. Shimazu, T. Desrochers, J. Feingold and Y. Ninokura and H. Hall for their technical advice, and D. Pizzagalli, R. Desimone, K. Goosens, J. Goldberg, D. Pfaff and Y. Kubota for reading the manuscript in draft form. This work was supported by a US National Institutes of Health Javits Merit grant (R01 NS025529), the Office of Naval Research (N000140710903), the Lynn Diamond Fellowship of the National Parkinson Foundation and Mr. Ira J. Jaffe.

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Affiliations

  1. McGovern Institute for Brain Research, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Ken-ichi Amemori
    •  & Ann M Graybiel

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Contributions

K.A. and A.M.G. designed the experiments and performed the surgeries. K.A. collected the data. K.A. and A.M.G. analyzed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ann M Graybiel.

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DOI

https://doi.org/10.1038/nn.3088

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