Conscious and unconscious brain responses to food and cocaine cues


Visual presentation of appetitive and negative cues triggers fast responses in the human brain. Here we assessed functional MRI (fMRI) responses to food, cocaine, and neutral cues presented at a subliminal (“unconscious”, 33 ms) and supraliminal (“conscious”, 750 and 3000 ms) level in healthy, cocaine naïve volunteers. Because there is evidence of circadian variability in reward sensitivity, our second aim was to assess diurnal variability in the brain’s reactivity to cues. Sixteen participants completed two randomly ordered fMRI sessions (once 9-11 AM and another 5–7 PM). in which food, cocaine, and neutral cues were presented for 33, 750 and 3000 ms. Participants rated food cues as positive and “wanted” (more so in evenings than mornings), and cocaine cues as negative (no diurnal differences). fMRI showed occipital cortex activation for food>neutral, cocaine>neutral and cocaine>food; dorsolateral prefrontal cortex for cocaine>neutral and cocaine>food, and midbrain for cocaine>food (all pFWE < 0.05). When comparing unconscious (33 ms) > conscious (750 and 3000 ms) presentations, we observed significant differences for cocaine>neutral and cocaine>food in occipital cortex, for cocaine>neutral in the insula/temporal lobe, and for food>neutral in the middle temporal gyrus (pFWE < 0.05). No diurnal differences for brain activations were observed. We interpret these findings to suggest that negative items (e.g., cocaine) might be perceived at a faster speed than positive ones (e.g., food), although we cannot rule out that the higher saliency of cocaine cues, which would be novel to non-drug using individuals, contributed to the faster speed of detection.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on request.


  1. Baltazar, R. M., Coolen, L. M., & Webb, I. C. (2013). Diurnal rhythms in neural activation in the mesolimbic reward system: Critical role of the medial prefrontal cortex. The European Journal of Neuroscience, 38(2), 2319–2327.

    Article  PubMed  Google Scholar 

  2. Boivin, D. B., Czeisler, C. A., Dijk, D. J., Duffy, J. F., Folkard, S., Minors, D. S., Totterdell, P., & Waterhouse, J. M. (1997). Complex interaction of the sleep-wake cycle and circadian phase modulates mood in healthy subjects. Archives of General Psychiatry, 54(2), 145–152.

    CAS  Article  Google Scholar 

  3. Byrne, J. E., Hughes, M. E., Rossell, S. L., Johnson, S. L., & Murray, G. (2017). Time of day differences in neural reward functioning in healthy Young men. The Journal of Neuroscience, 37(37), 8895–8900.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Byrne, J. E., & Murray, G. (2017). Diurnal rhythms in psychological reward functioning in healthy young men: 'Wanting', liking, and learning. Chronobiology International, 34(2), 287–295.

    Article  PubMed  Google Scholar 

  5. Cabrera, E. A., Wiers, C. E., Lindgren, E., Miller, G., Volkow, N. D., & Wang, G. J. (2016). Neuroimaging the effectiveness of substance use disorder treatments. Journal of Neuroimmune Pharmacology, 11(3), 408–433.

    Article  PubMed  Google Scholar 

  6. Carlsson, K., Petersson, K. M., Lundqvist, D., Karlsson, A., Ingvar, M., & Ohman, A. (2004). Fear and the amygdala: Manipulation of awareness generates differential cerebral responses to phobic and fear-relevant (but nonfeared) stimuli. Emotion, 4(4), 340–353.

    Article  PubMed  Google Scholar 

  7. Castellanos, E. H., Charboneau, E., Dietrich, M. S., Park, S., Bradley, B. P., Mogg, K., & Cowan, R. L. (2009). Obese adults have visual attention bias for food cue images: Evidence for altered reward system function. International Journal of Obesity, 33(9), 1063–1073.

    CAS  Article  PubMed  Google Scholar 

  8. Childress, A. R., Ehrman, R. N., Wang, Z., Li, Y., Sciortino, N., Hakun, J., Jens, W., Suh, J., Listerud, J., Marquez, K., Franklin, T., Langleben, D., Detre, J., & O'Brien, C. P. (2008). Prelude to passion: Limbic activation by "unseen" drug and sexual cues. PLoS One, 3(1), e1506.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Frank, S., Laharnar, N., Kullmann, S., Veit, R., Canova, C., Hegner, Y. L., Fritsche, A., & Preissl, H. (2010). Processing of food pictures: Influence of hunger, gender and calorie content. Brain Research, 1350, 159–166.

    CAS  Article  PubMed  Google Scholar 

  10. Hare, T. A., Camerer, C. F., & Rangel, A. (2009). Self-control in decision-making involves modulation of the vmPFC valuation system. Science, 324(5927), 646–648.

    CAS  Article  PubMed  Google Scholar 

  11. Ihssen, N., Cox, W. M., Wiggett, A., Fadardi, J. S., & Linden, D. E. (2011). Differentiating heavy from light drinkers by neural responses to visual alcohol cues and other motivational stimuli. Cerebral Cortex, 21(6), 1408–1415.

    Article  PubMed  Google Scholar 

  12. Jastreboff, A. M., Sinha, R., Lacadie, C., Small, D. M., Sherwin, R. S., & Potenza, M. N. (2013). Neural correlates of stress- and food cue-induced food craving in obesity: Association with insulin levels. Diabetes Care, 36(2), 394–402.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (2008). International affective picture system (IAPS): Affective ratings of pictures and instruction manual. (technical report A-8). From University of Florida.

  14. Larson, C. L., Schaefer, H. S., Siegle, G. J., Jackson, C. A., Anderle, M. J., & Davidson, R. J. (2006). Fear is fast in phobic individuals: Amygdala activation in response to fear-relevant stimuli. Biological Psychiatry, 60(4), 410–417.

    Article  PubMed  Google Scholar 

  15. Lindgren, E., Gray, K., Miller, G., Tyler, R., Wiers, C. E., Volkow, N. D., & Wang, G. J. (2018). Food addiction: A common neurobiological mechanism with drug abuse. Front Biosci (Landmark Ed), 23, 811–836.

    CAS  Article  Google Scholar 

  16. Lipka, J., Miltner, W. H., & Straube, T. (2011). Vigilance for threat interacts with amygdala responses to subliminal threat cues in specific phobia. Biological Psychiatry, 70(5), 472–478.

    Article  PubMed  Google Scholar 

  17. Ludwig, V. U., Stelzel, C., Krutiak, H., Magrabi, A., Steimke, R., Paschke, L. M., Kathmann, N., & Walter, H. (2014). The suggestible brain: Posthypnotic effects on value-based decision-making. Social Cognitive and Affective Neuroscience, 9(9), 1281–1288.

    Article  PubMed  Google Scholar 

  18. Murray, G., Nicholas, C. L., Kleiman, J., Dwyer, R., Carrington, M. J., Allen, N. B., & Trinder, J. (2009). Nature's clocks and human mood: The circadian system modulates reward motivation. Emotion, 9(5), 705–716.

    Article  PubMed  Google Scholar 

  19. Siegel, P., Warren, R., Wang, Z., Yang, J., Cohen, D., Anderson, J. F., Murray, L., & Peterson, B. S. (2017). Less is more: Neural activity during very brief and clearly visible exposure to phobic stimuli. Human Brain Mapping, 38(5), 2466–2481.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Smith, N. K., Cacioppo, J. T., Larsen, J. T., & Chartrand, T. L. (2003). May I have your attention, please: Electrocortical responses to positive and negative stimuli. Neuropsychologia, 41(2), 171–183.

    Article  Google Scholar 

  21. Volkow, N. D., Fowler, J. S., Wang, G. J., Telang, F., Logan, J., Jayne, M., Ma, Y., Pradhan, K., Wong, C., & Swanson, J. M. (2010). Cognitive control of drug craving inhibits brain reward regions in cocaine abusers. Neuroimage, 49(3), 2536–2543.

    Article  PubMed  Google Scholar 

  22. Volkow, N. D., Tomasi, D., Wang, G. J., Fowler, J. S., Telang, F., Goldstein, R. Z., et al. (2011). Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers. PLoS One, 6(2), e16573.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Volkow, N. D., Wang, G. J., Fowler, J. S., & Telang, F. (2008). Overlapping neuronal circuits in addiction and obesity: Evidence of systems pathology. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 363(1507), 3191–3200.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Childress, A. R., Jayne, M., Ma, Y., & Wong, C. (2006). Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction. The Journal of Neuroscience, 26(24), 6583–6588.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Wang, G. J., Tomasi, D., Volkow, N. D., Wang, R., Telang, F., Caparelli, E. C., & Dunayevich, E. (2014). Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues. International Journal of Obesity, 38(5), 682–688.

    CAS  Article  PubMed  Google Scholar 

  26. Webb, I. C., Baltazar, R. M., Wang, X., Pitchers, K. K., Coolen, L. M., & Lehman, M. N. (2009). Diurnal variations in natural and drug reward, mesolimbic tyrosine hydroxylase, and clock gene expression in the male rat. Journal of Biological Rhythms, 24(6), 465–476.

    CAS  Article  PubMed  Google Scholar 

  27. Wetherill, R. R., Childress, A. R., Jagannathan, K., Bender, J., Young, K. A., Suh, J. J., O'Brien, C. P., & Franklin, T. R. (2014). Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals. Psychopharmacology, 231(7), 1397–1407.

    CAS  Article  PubMed  Google Scholar 

  28. Wiers, C. E., Stelzel, C., Gladwin, T. E., Park, S. Q., Pawelczack, S., Gawron, C. K., Stuke, H., Heinz, A., Wiers, R. W., Rinck, M., Lindenmeyer, J., Walter, H., & Bermpohl, F. (2015). Effects of cognitive bias modification training on neural alcohol cue reactivity in alcohol dependence. The American Journal of Psychiatry, 172(4), 335–343.

    Article  PubMed  Google Scholar 

  29. Wiers, C. E., Stelzel, C., Park, S. Q., Gawron, C. K., Ludwig, V. U., Gutwinski, S., Heinz, A., Lindenmeyer, J., Wiers, R. W., Walter, H., & Bermpohl, F. (2014). Neural correlates of alcohol-approach Bias in alcohol addiction: The Spirit is willing but the flesh is weak for spirits. Neuropsychopharmacology, 39(3), 688–697.

    Article  PubMed  Google Scholar 

  30. Wilcox, C. E., Teshiba, T. M., Merideth, F., Ling, J., & Mayer, A. R. (2011). Enhanced cue reactivity and fronto-striatal functional connectivity in cocaine use disorders. Drug and Alcohol Dependence, 115(1–2), 137–144.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Williams, L. M., Palmer, D., Liddell, B. J., Song, L., & Gordon, E. (2006). The 'when' and 'where' of perceiving signals of threat versus non-threat. Neuroimage, 31(1), 458–467.

    Article  PubMed  Google Scholar 

  32. Zaldivar, D., Goense, J., Lowe, S. C., Logothetis, N. K., & Panzeri, S. (2018). Dopamine is signaled by mid-frequency oscillations and boosts output layers visual information in visual cortex. Curr Biol, 28(2), 224–235.e225.

    CAS  Article  PubMed  Google Scholar 

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We thank Karen Torres, Lori Talagala, Nancy Diazgranados, Tom Lionetti, Dave Spero, Yvonne Horneffer, and Minoo McFarland for their contributions.


This work was supported by the National Institute on Alcohol Abuse and Alcoholism (Y1AA-3009 to NDV).

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Correspondence to Corinde E. Wiers or Nora D. Volkow.

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Wiers, C.E., Zhao, J., Manza, P. et al. Conscious and unconscious brain responses to food and cocaine cues. Brain Imaging and Behavior 15, 311–319 (2021).

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  • Appetite
  • Consciousness
  • Emotion
  • Visual awareness