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Persistent neuronal activity in human prefrontal cortex links perception and action

Nature Human Behaviourvolume 2pages8091 (2018) | Download Citation


How do humans flexibly respond to changing environmental demands on a subsecond temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behaviour, yet the core mechanisms that translate sensory information into behaviour remain undefined. Using direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity (indexed by the broadband gamma signal) in 16 participants while they performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centred in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behaviour.

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We thank the patients for their cooperation, patience, and interest—without their help this research would not be possible. We also thank J. N. Hoffman, A. Flinker, R. Ivry, K. Johnson and J. D. Wallis for providing valuable comments and suggestions during manuscript preparation, and K. L. Anderson, M. Cano and V. N. Rangarajan for help in data collection.

This work was supported by the following grants: National Science Foundation (NSF) Graduate Research Fellowship DGE1106400 (M.H.), the National Institute of Mental Health F32MH75317 (A.S.), the National Institute of Neurological Disorders and Stroke (NINDS) R37NS21135 and the Nielsen Corporation (R.T.K.), NINDS R01NS078396 and NSF BCS1358907 (J.P.), NS40596 and NS088606 (N.E.C.), NIH R01DC012379 (E.F.C.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The MacBrain Face Stimulus Set was developed by Nim Tottenham ( with support from the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. The dog–cat morph stimuli were provided by E. Miller from the Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology.

Author information


  1. Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA

    • Matar Haller
    • , Robert T. Knight
    •  & Avgusta Y. Shestyuk
  2. Department of Psychology, University of California, Berkeley, CA, USA

    • John Case
    •  & Robert T. Knight
  3. Department of Neurology, The Johns Hopkins University Medical School, Baltimore, MD, USA

    • Nathan E. Crone
  4. Departments of Neurological Surgery, UCSF Center for Integrative Neuroscience, University of California, San Francisco, CA, USA

    • Edward F. Chang
  5. Department of Neurology and Neurosurgery, California Pacific Medical Center, San Francisco, CA, USA

    • David King-Stephens
    • , Kenneth D. Laxer
    •  & Peter B. Weber
  6. Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA

    • Josef Parvizi


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M.H., A.S. and R.T.K. conceived the study. M.H. and A.S. designed the experiments and collected the data. J.P., E.F.C., N.E.C., D.K.S., K.D.L. and P.B.W. recruited and examined the participants and facilitated data recording. M.H., J.C. and A.Y.S. analysed and interpreted the data. M.H., A.Y.S. and R.T.K. wrote the manuscript. A.Y.S. provided direct supervision during study design, data collection, data analysis and interpretation, and manuscript preparation stages.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Avgusta Y. Shestyuk.

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    Supplementary Notes, Supplementary Methods, Supplementary Tables 1–6, Supplementary Figures 1–14.

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