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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Duncan, J., Burgess, P. & Emslie, H. Fluid intelligence after frontal lobe lesions. Neuropsychologia 33, 261–268 (1995).
Fuster, J. M., Bodner, M. & Kroger, J. K. Cross-modal and cross-temporal association in neurons of frontal cortex. Nature 405, 347–351 (2000).
Stuss, D. T. & Knight, R. T. Principles of Frontal Lobe Function (Oxford Univ. Press, New York, NY, 2012).
Szczepanski, S. M. & Knight, R. T. Insights into human behavior from lesions to the prefrontal cortex. Neuron 83, 1002–1018 (2014).
Callicott, J. H. et al. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb. Cortex 10, 1078–1092 (2000).
Just, M. A., Cherkassky, V. L., Keller, T. A. & Minshew, N. J. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain 127, 1811–1821 (2004).
Mayberg, H. in Frontal-Subcortical Circuits in Psychiatric and Neurological Disorders (eds Cummings, J. L. & Lichter, D. G.) 177–206 (Guilford, New York, NY, 2001).
Curtis, C. E. & Lee, D. Beyond working memory: the role of persistent activity in decision making. Trends Cogn. Sci. 14, 216–222 (2010).
D’Esposito, M. & Postle, B. R. The cognitive neuroscience of working memory. Annu. Rev. Psychol. 66, 115–142 (2015).
Fedorenko, E., Duncan, J. & Kanwisher, N. Broad domain generality in focal regions of frontal and parietal cortex. Proc. Natl Acad. Sci. USA 110, 16616–16621 (2013).
Goard, M. J., Pho, G. N., Woodson, J. & Sur, M. Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions. eLife 5, e13764 (2016).
Hernandez, A., Zainos, A. & Romo, R. Temporal evolution of a decision-making process in medial premotor cortex. Neuron 33, 959–972 (2002).
Kim, J. N. & Shadlen, M. N. Neural correlates of a decision in the dorsolateral prefrontal cortex of the macaque. Nat. Neurosci. 2, 176–185 (1999).
Rainer, G., Rao, S. C. & Miller, E. K. Prospective coding for objects in primate prefrontal cortex. J. Neurosci. 19, 5493–5505 (1999).
Riley, M. R. & Constantinidis, C. Role of prefrontal persistent activity in working memory. Front. Syst. Neurosci. 9, 181 (2016).
Siegel, M., Buschman, T. J. & Miller, E. K. Cortical information flow during flexible sensorimotor decisions. Science 348, 1352–1355 (2015).
Stokes, M. G. ‘Activity-silent’ working memory in prefrontal cortex: a dynamic coding framework. Trends Cogn. Sci. 19, 394–405 (2015).
Chafee, M. V. & Goldman-Rakic, P. S. Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task. J. Neurophysiol. 79, 2919–2940 (1998).
Huang, Y., Matysiak, A., Heil, P., Konig, R. & Brosch, M. Persistent neural activity in auditory cortex is related to auditory working memory in humans and nonhuman primates. eLife 5, e15441 (2016).
Romo, R. & De Lafuente, V. Conversion of sensory signals into perceptual decisions. Prog. Neurobiol. 103, 41–75 (2013).
Curtis, C. E., Rao, V. Y. & D’Esposito, M. Maintenance of spatial and motor codes during oculomotor delayed response tasks. J. Neurosci. 24, 3944–3952 (2004).
Curtis, C. E. & Connolly, J. D. Saccade preparation signals in the human frontal and parietal cortices. J. Neurophysiol. 99, 133–145 (2008).
Bastin, J. et al. Direct recordings in human cortex reveal the dynamics of gamma-band (50–150 Hz) activity during pursuit eye movement control. Neuroimage 63, 339–347 (2012).
Edwards, E. et al. Spatiotemporal imaging of cortical activation during verb generation and picture naming. Neuroimage 50, 291–301 (2010).
Ossandon, T. et al. Efficient ‘Pop-Out’ visual search elicits sustained broadband gamma activity in the dorsal attention network. J. Neurosci. 32, 3414–3421 (2012).
Manning, J. R., Jacobs, J., Fried, I. & Kahana, M. J. Broadband shifts in local field potential power spectra are correlated with single-neuron spiking in humans. J. Neurosci. 29, 13613–20 (2009).
Mukamel, R. et al. Coupling between neuronal firing, field potentials, and fMRI in human auditory cortex. Science 309, 951–954 (2005).
Ray, S., Crone, N. E., Niebur, E., Franaszczuk, P. J. & Hsiao, S. S. Neural correlates of high-gamma oscillations (60–200 Hz) in macaque local field potentials and their potential implications in electrocorticography. J. Neurosci. 28, 11526–11536 (2008).
Ray, S. & Maunsell, J. H. R. Different origins of gamma rhythm and high-gamma activity in macaque visual cortex. PLoS Biol. 9, e1000610 (2011).
Flinker, A. et al. Redefining the role of Broca’s area in speech. Proc. Natl Acad. Sci. USA 112, 2871–2875 (2015).
Fedorenko, E., Duncan, J. & Kanwisher, N. Language-selective and domain-general regions lie side by side within Broca’s area. Curr. Biol. 22, 2059–2062 (2012).
Sahin, N. T., Pinker, S., Cash, S. S., Schomer, D. & Halgren, E. Sequential processing of lexical, grammatical, and phonological information within Broca’s area. Science 326, 445–449 (2009).
Braun, U. et al. Dynamic reconfiguration of frontal brain networks during executive cognition in humans. Proc. Natl Acad. Sci. USA 112, 11678–11683 (2015).
Murray, J. D. et al. A hierarchy of intrinsic timescales across primate cortex. Nat. Neurosci. 17, 1661–1663 (2014).
Catani, M. et al. Short frontal lobe connections of the human brain. Cortex 48, 273–291 (2012).
Sreenivasan, K. K., Curtis, C. E. & D’Esposito, M. Revisiting the role of persistent neural activity during working memory. Trends Cogn. Sci. 18, 82–89 (2014).
Duncan, J. & Owen, A. M. Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci. 23, 475–483 (2000).
Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C. & Wager, T. D. Large-scale automated synthesis of human functional neuroimaging data. Nat. Methods 8, 665–670 (2011).
Miller, E. K. & Cohen, J. D. An integrative theory of prefrontal cortex function. Annu. Rev. Neurosci. 24, 167–202 (2001).
Cohen, J. D. et al. Temporal dynamics of brain activation during a working memory task. Nature 386, 604–608 (1997).
Mukamel, R. & Fried, I. Human intracranial recordings and cognitive neuroscience. Annu. Rev. Psychol. 63, 511–537 (2012).
Lundqvist, M. et al. Gamma and beta bursts underlie working memory. Neuron 90, 152–164 (2016).
Tottenham, N. et al. The NimStim set of facial expressions: judgments from untrained research participants. Psychiat. Res. 168, 242–249 (2009).
Kominek, J. & Black, A. W. The CMU Arctic speech databases. In: Fifth ISCA Speech Synthesis Workshop (eds Black, A. W. & Lenzo, K.) 223–224 (2004).
Kawahara, H. & Irino, T. in Speech Separation by Humans and Machines (ed. Divenyi, P.) 167–180 (Springer, Boston, MA, 2005).
Freedman, D. J., Riesenhuber, M., Poggio, T. & Miller, E. K. Categorical representation of visual stimuli in the primate prefrontal cortex. Science 291, 312–316 (2001).
Bradley, M. M. & Lang, P. J. Affective Norms for English words (ANEW): Instruction Manual and Affective Ratings Technical Report C-1 (Center for Research in Psychophysiology, Univ. Florida, 1999).
Crone, N. Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. II. Event-related synchronization in the gamma band. Brain 121, 2301–2315 (1998).
Lachaux, J.-P., Axmacher, N., Mormann, F., Halgren, E. & Crone, N. E. High-frequency neural activity and human cognition: Past, present and possible future of intracranial EEG research. Prog. Neurobiol. 98, 279–301 (2012).
Miller, K. J. et al. Broadband changes in the cortical surface potential track activation of functionally diverse neuronal populations. Neuroimage 85, 711–720 (2014).
Bruns, A. Fourier-, Hilbert- and wavelet-based signal analysis: Are they really different approaches? J. Neurosci. Methods 137, 321–332 (2004).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B 57, 298–300 (1995).
Ruscio, J. & Roche, B. Determining the number of factors to retain in an exploratory factor analysis using comparison data of known factorial structure. Psychol. Assess. 24, 282–292 (2012).
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 (email@example.com) 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.
The authors declare no competing interests.
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Haller, M., Case, J., Crone, N.E. et al. Persistent neuronal activity in human prefrontal cortex links perception and action. Nat Hum Behav 2, 80–91 (2018). https://doi.org/10.1038/s41562-017-0267-2
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