, Volume 234, Issue 1, pp 53–62 | Cite as

Electro-physiological changes in the brain induced by caffeine or glucose nasal spray

  • K De Pauw
  • B Roelands
  • J Van Cutsem
  • U Marusic
  • T Torbeyns
  • R MeeusenEmail author
Original Investigation



A direct link between the mouth cavity and the brain for glucose (GLUC) and caffeine (CAF) has been established. The aim of this study is to determine whether a direct link for both substrates also exist between the nasal cavity and the brain.


Ten healthy male subjects (age 22 ± 1 years) performed three experimental trials, separated by at least 2 days. Each trial included a 20-s nasal spray (NAS) period in which solutions placebo (PLAC), GLUC, or CAF were provided in a double-blind, randomized order. During each trial, four cognitive Stroop tasks were performed: two familiarization trials and one pre- and one post-NAS trial. Reaction times and accuracy for different stimuli (neutral, NEUTR; congruent, CON; incongruent INCON) were determined. Electroencephalography was continuously measured throughout the trials. During the Stroop tasks pre- and post-NAS, the P300 was assessed and during NAS, source localization was performed using standardized low-resolution brain electromagnetic tomography (sLORETA).

Results and discussion

NAS activated the anterior cingulate cortex (ACC). CAF-NAS also increased θ and β activity in frontal cortices. Furthermore, GLUC-NAS increased the β activity within the insula. GLUC-NAS also increased the P300 amplitude with INCON (P = 0.046) and reduced P300 amplitude at F3-F4 and P300 latency at CP1-CP2-Cz with NEUTR (P = 0.001 and P = 0.016, respectively). The existence of nasal bitter and sweet taste receptors possibly induce these brain responses.


Greater cognitive efficiency was observed with GLUC-NAS. CAF-NAS activated cingulate, insular, and sensorymotor cortices, whereas GLUC-NAS activated sensory, cingulate, and insular cortices. However, no effect on the Stroop task was found.


EEG Stroop Attention ERP P300 Source localization sLORETA 



BR is a postdoctoral fellow of the Fund for Scientific Research Flanders (FWO).

Compliance with ethical standards

The experiment was approved by the institutional medical ethical committee of UZ Brussel and Vrije Universiteit Brussel (Belgium) (B.U.N. 143201421380). The subjects were provided written and oral information about the experimental procedures and potential risks before giving informed consent to participate in this study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Barbas H (1995) Anatomical basis of cognitive-emotional interactions in the primate prefrontal cortex. Neurosci Biobehav Rev 19:499–510PubMedCrossRefGoogle Scholar
  2. Barham HP, Cooper SE, Anderson CB, Tizzano M, Kingdom TT, Finger TE, Kinnamon SC, Ramakrishnan VR (2013) Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa. Int Forum Allergy Rhinol 3(6):450–457PubMedPubMedCentralCrossRefGoogle Scholar
  3. Beaven CM, Maulder P, Pooley A, Kilduff L, Cook C (2013) Effects of caffeine and carbohydrate mouth rinses on repeated sprint performance. Appl Physiol Nutr Metab 38(6):633–637PubMedCrossRefGoogle Scholar
  4. Benton D, Owens DS, Parker PY (1994) Blood glucose influences memory and attention in young adults. Neuropsychologia 32:595–607PubMedCrossRefGoogle Scholar
  5. Bottoms L, Greenhalgh A, Gregory K (2013) The effect of caffeine ingestion on skill maintenance and fatigue in epee fencers. J Sports Sci 31(10):1091–2099PubMedCrossRefGoogle Scholar
  6. Brandt KR, Gibson EL, Rackie JM (2013) Differential facilitative effects of glucose administration on Stroop task conditions. Behav Neurosci 127(6):932–935PubMedCrossRefGoogle Scholar
  7. Braun T, Mack B, Kramer MF (2011) Solitary chemosensory cells in the respiratory and vomeronasal epithelium of the human nose: a pilot study. Rhinology 49(5):507–512PubMedGoogle Scholar
  8. Brown LA, Riby LM (2013) Glucose enhancement of event-related potentials associated with episodic memory and attention. Food Funct 4:770–776PubMedCrossRefGoogle Scholar
  9. Burke LM, Maughan RJ (2015) The governor has a sweet tooth—mouth sensing of nutrients to enhance sports performance. European. J Sports Sci 15(1):29–40Google Scholar
  10. Chambers ES, Bridge MW, Jones DA (2009) Carbohydrate sensing in the human mouth: effects on exercise performance and brain activity. J Physiol 587(Pt 8):1779–1794PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chan AS, Cheung MC, Sze SL, Leung WW, Shi D (2011) An herbal drop enhanced frontal and anterior cingulated cortex activity. Evid Based Complement Alternat Med 2011:543648PubMedPubMedCentralGoogle Scholar
  12. Coles M, Smid H, Scheffers M, Otten L (1995) Mental chronometry and the study of human information processing. In: Rugg M, Coles M (eds) Electrophysiology of the mind: event-related brain potentials and cognition. Oxford Psychology Series, Oxford, pp. 86–131Google Scholar
  13. de Araujo IE, Ren X, Ferreira JG (2010) Metabolic sensing in brain dopamine systems. Results Probl Cell Differ 52:69–86PubMedCrossRefGoogle Scholar
  14. de Araujo IET, Rolls ET, Kringelbach ML, McGlone F, Phillips N (2003) Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain. Eur J Neurosci 18:2059–2068PubMedCrossRefGoogle Scholar
  15. De Pauw K, Roelands B, Cheung SS, de Geus B, Rietjens G, Meeusen R (2013) Guidelines to classify subject groups in sport-science research. Int J Sports Physiol Perform 8:111–122PubMedCrossRefGoogle Scholar
  16. De Pauw K, Roelands B, Knaepen K, Polfliet M, Stiens J, Meeusen R (2015) Effects of caffeine and maltodextrin mouth rinsing on P300, brain imaging, and cognitive performance. J Appl Physiol (1985) 118(6):776–782CrossRefGoogle Scholar
  17. Deslandes AC, Veiga H, Cagy M, Piedade R, Pompeu F, Ribeiro P (2004) Effects of caffeine on visual evoked potential (P300) and neuromotor performance. Arq Neuropsiquiatr 62(2-B):385–390PubMedCrossRefGoogle Scholar
  18. Deslandes AC, Veiga H, Cagy M, Piedade R, Pompeu F, Ribeiro P (2005) Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system. Braz J Med Biol Res 38:1077–1086PubMedCrossRefGoogle Scholar
  19. Devillier P, Naline E, Grassin-Delyle S (2015) The pharmacology of bitter taste receptors and their role in human airways. Pharmacol Ther 155:11–21PubMedCrossRefGoogle Scholar
  20. Diukova A, Ware J, Smith JE, Evans CJ, Murphy K, Rogers PJ, Wise RG (2012) Separating neural and vascular effects of caffeine using simultaneous EEG-fMRI: differential effects of caffeine on cognitive and sensorimotor brain responses. NeuroImage 62:239–249PubMedPubMedCentralCrossRefGoogle Scholar
  21. Donchin E, Karis D, Bashore TR, Coles MGH, Gratton G (1986) Cognitive psychophysiology: systems, processes, and applications. In: Coles MGH, Donchin E, Porges S (eds) Psychophysiology: systems, processes, and applications. The Guilford Press, New York, pp. 244–267Google Scholar
  22. Edwards S, Brice C, Craig C, Penri-Jones R (1996) Effects of caffeine, practice, and mode of presentation on Stroop task performance. Pharmacol Biochem Behav 54(2):309–315PubMedCrossRefGoogle Scholar
  23. Fisher RA (1935) The design of experiment. Hafner, New YorkGoogle Scholar
  24. Gagnon C, Desjardins-Crépeau L, Tournier I, Desjardins M, Lesage F, Greenwood CE, Bherer L (2012) Near-infrared imaging of the effects of glucose ingestion and regulation on prefrontal activation during dual-task execution in healthy fasting older adults. Behav Brain Res 232:137–147PubMedCrossRefGoogle Scholar
  25. Gagnon C, Greenwood CE, Bherer L (2010) The acute effects of glucose ingestion on attentional control in fasting healthy older adults. Psychopharmacology 211:337–346PubMedCrossRefGoogle Scholar
  26. Geisler MW, Polich J (1994) P300 is unaffected by glucose increase. Biol Psychol 37:235–245PubMedCrossRefGoogle Scholar
  27. Gevins A, Smith ME, McEvoy L, Yu D (1997) High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cereb Cortex 7(4):374–385PubMedCrossRefGoogle Scholar
  28. Giles GE, Mahoney CR, Brunyé TT, Gardony AL, Taylor HA, Kanarek RB (2012) Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose. Pharmacol Biochem Behav 102:569–577PubMedCrossRefGoogle Scholar
  29. Grandjean J, D’Ostilio K, Phillips C, Balteau E, Degueldre C, Luxen A, Maquet P, Salmon E, Collette F (2012) Modulation of brain activity during a Stroop inhibitory task by the kind of cognitive control required. PLoS One 7(7):e41513PubMedPubMedCentralCrossRefGoogle Scholar
  30. Hameleers PAHM, Van Boxtel MPJ, Hogervorst E, Riedel WJ, Houx PJ, Buntinx F, Jolles J (2000) Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups. Hum Psychopharmacol Clin Exp 15:573–581CrossRefGoogle Scholar
  31. Hoffman JE (1990) Event-related potentials and automatic and controlled processes. In: Rohrbaugh JW, Parasuraman R, Johnson Jr R (eds) Event related brain potentials. Oxford University Press, New York, pp. 145–157Google Scholar
  32. Hogervorst E, Bandelow S, Schmitt J, Jentjens R, Oliveira M, Allgrove J, Carter T, Gleeson M (2008) Caffeine improves physical and cognitive performance during exhaustive exercise. Med Sci Sports Exerc 40(10):1841–1851PubMedCrossRefGoogle Scholar
  33. Jasper HH (1958) Report of the committee on methods of clinical examination in electroencephalography. Electroencephalogr Clin Neurophysiol 10:370–371CrossRefGoogle Scholar
  34. Jeukendrup AE, Rollo I, Carter JM (2013) Carbohydrate mouth rinse: performance effects and mechanisms. Sports Science Exchange 26(118):1–8Google Scholar
  35. Jogani V, Jinturkar K, Vyas T, Misra A (2008) Recent patents review on intranasal administration for CNS drug delivery. Recent Patents on Drug Delivery and Formulation 2:25–40PubMedCrossRefGoogle Scholar
  36. Knott V, Messier C, Mahoney C, Gagnon M (2001) Glucose and glucoregulatory modulation of memory scanning, event-related potentials and EEG in elderly subjects. Neuropsychobiology 44:156–166PubMedCrossRefGoogle Scholar
  37. Koski L, Paus T (2000) Functional connectivity of the anterior cingulate cortex within the human frontal lobe: a brainmapping meta-analysis. Exp Brain Res 133(1):55–65PubMedCrossRefGoogle Scholar
  38. Kringelbach ML (2004) Food for thought: hedonic experience beyond homeostasis in the human brain. Neuroscience 126:807–819PubMedCrossRefGoogle Scholar
  39. Laird AR, McMillan KM, Lancaster JL, Kochunov P, Turkeltaub PE, Pardo JV, Fox PT (2005) A comparison of label-based review and ALE meta-analysis in the Stroop task. Hum Brain Mapp 25(1):6–21PubMedCrossRefGoogle Scholar
  40. Lee RJ, Cohen NA (2014) Bitter and sweet taste receptors in the respiratory epithelium in health and disease. J Mol Med 92:1235–1244PubMedPubMedCentralCrossRefGoogle Scholar
  41. Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B, Doghramji L, Xiong G, Adappa ND, Palmer JN, Kennedy DW, Kreindler JL, Margolskee RF, Cohen NA (2014) Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest 124(3):1393–1405PubMedPubMedCentralCrossRefGoogle Scholar
  42. Lorist MM, Tops M (2003) Caffeine, fatigue and cognition. Brain Cogn 53:82–94PubMedCrossRefGoogle Scholar
  43. Lorist MM, Snel J, Kok A (1994) Influence of caffeine on information processing stages in well rested and fatigued subjects. Psychopharmacology 113:411–421PubMedCrossRefGoogle Scholar
  44. Lorist MM, Snel J, Kok A, Mulder G (1996) Acute effects of caffeine on selective attention and visual research processes. Psychophysiology 33:354–361PubMedCrossRefGoogle Scholar
  45. Martin FH, Garfield J (2006) Combined effects of alcohol and caffeine on the late components of the event-related potential and on reaction time. Biol Psychol 71:63–73PubMedCrossRefGoogle Scholar
  46. Messier C (2004) Glucose improvement of memory: a review. Eur J Pharmacol 490:33–57PubMedCrossRefGoogle Scholar
  47. Nee DE, Wager TD, Jonides J (2007) Interference resolution; insights from a meta-analysis of neuroimaging tasks. Cognitive, Affective and Behavioral Neuroscience 7:1–17PubMedCrossRefGoogle Scholar
  48. Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25PubMedCrossRefGoogle Scholar
  49. Niedermeyer E, Lopes da Silva F (2005) Electroencephalography: basic principles, clinical applications, and related fields. Lippincott, Williams and Wilkins, PhiladelphiaGoogle Scholar
  50. Pandey AK, Kamarajan C, Tang Y, Chorlian DB, Roopesh BN, Manz N, Stimus A, Rangaswamy M, Porjesz B (2012) Neurocognitive deficits in male alcoholics: an ARP/sLORETA analysis of the N2 component in an equal probability Go/NoGo task. Biol Psychol 89:170–182PubMedCrossRefGoogle Scholar
  51. Pascual-Marqui RD, Esslen M, Kechi K, Lehmann D (2002) Functional imaging with low resolution brain electromagnetic tomography (LORETA): review, new comparisons, and validation. Japanese. J Clin Neurophysiol 30:81–94Google Scholar
  52. Patel SH, Azzam PN (2005) Characterization of N200 and P300: selected studies of the event-related potential. Int J Med Sci 2(4):147–154PubMedPubMedCentralCrossRefGoogle Scholar
  53. Pires A, Fortuna A, Alves G, Falcão A (2009) Intranasal drug delivery: how, why and what for? J Pharm Pharmaceut Sci 12(3):288–311CrossRefGoogle Scholar
  54. Polich J, Criado JR (2006) Neuropsychology and neuropharmacology of P3a and P3b. Int J Psychophysiol 60(2):172–185PubMedCrossRefGoogle Scholar
  55. Reeves R, Struve F, Patrick G (1999) The effects of caffeine withdrawal on cognitive P300 auditory and visual evoked potentials. Clin Electroencephalogr 30:24–27PubMedCrossRefGoogle Scholar
  56. Riby LM, Sünram-Lea SI, Graham C, Foster JK, Cooper T, Moodie C, Gunn VP (2008) The P3b versus the P3a: an event-related potential investigation of the glucose facilitation effect. J Psychopharmacol (Oxf) 22:486–492CrossRefGoogle Scholar
  57. Roberts KL, Hall DA (2008) Examining a supramodal network for conflict processing. A systematic review and novel functional magnetic resonance imaging data for related visual and auditory Stroop tasks. J Cogn Neurosci 20:1063–1078PubMedCrossRefGoogle Scholar
  58. Ruijter J, Lorist MM, Snel J (1999) The influence of different doses of caffeine on visual task performance. J Psychophysiol 13:37–48CrossRefGoogle Scholar
  59. Ruijter J, Lorist MM, Snel J, De Ruijter MB (2000) The influence of caffeine on sustained attention: an ERP study. Pharmacol Biochem Behav 66:29–37PubMedCrossRefGoogle Scholar
  60. Sacchetti C, Artusi M, Santi P, Colombo P (2002) Caffeine microparticles for nasal administration obtained by spray drying. Int J Pharm 242:335–339PubMedCrossRefGoogle Scholar
  61. Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ (2009) Motile cilia of human airway epithelia are chemosensory. Science 325(5944):1131–1134PubMedPubMedCentralCrossRefGoogle Scholar
  62. Sinclair J, Bottoms L, Flynn C, Bradley E, Alexander G, McCullagh S, Finn T, Hurst HT (2014) The effect of different durations of carbohydrate mouth rinse on cycling performance. Eur J Sport Sci 14(3):259–264PubMedCrossRefGoogle Scholar
  63. Small DM, Bender G, Veldhuizen MG, Rudenga K, Nachtigal D, Felsted J (2007) The role of the human orbitofrontal cortex in the taste and flavor processing. Ann N Y Acad Sci 1121:136–151PubMedCrossRefGoogle Scholar
  64. Smith MA, Riby LM, Sünram-Lea SI, van Eekelen JAM, Foster JK (2009) Glucose modulates event-related potential components of recollection and familiarity in healthy adolescents. Psychopharmacology 205:11–20PubMedCrossRefGoogle Scholar
  65. Smith A, Sutherland D, Christopher G (2005) Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers. J Psychopharmacol 19(6):620–626PubMedCrossRefGoogle Scholar
  66. Stevens A, Lowe J (1997) Human histology. Mosby, Philadelphia, USAGoogle Scholar
  67. Sünram-Lea SI, Foster JK, Durlach P, Perez C (2002) Investigation into the significance of task difficulty and divided allocation of resources on the glucose memory facilitation effect. Psychopharmacology 160(4):387–397PubMedCrossRefGoogle Scholar
  68. Tizzano M, Finger TE (2013) Chemosensors in the nose: guardians of the airways. Physiology 28:51–60PubMedPubMedCentralCrossRefGoogle Scholar
  69. Tizzano M, Cristofoletti M, Sbarbati A, Finger TE (2011) Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm Med 11:3PubMedPubMedCentralCrossRefGoogle Scholar
  70. Turner CE, Byblow WD, Stinear CM, Gant N (2014) Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception. Appetite 80:212–219PubMedCrossRefGoogle Scholar
  71. Wadell C, Björk E, Camber O (1999) Nasal drug delivery—evaluation of an in vitro model using porcine nasal mucosa. Eur J Pharm Sci 7:197–206PubMedCrossRefGoogle Scholar
  72. Wang C, Szabo JS, Dykman RA (2004) Effects of a carbohydrate supplement upon resting brain activity. Integr Physiol Behav Sci 39(2):126–138PubMedCrossRefGoogle Scholar
  73. Wickens C, Kramer A, Vanesse L, Donchin E (1983) The performance of concurrent tasks: a psychophysiological analysis of the reciprocity of information processing resource. Science 221:1080–1082PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • K De Pauw
    • 1
  • B Roelands
    • 1
    • 2
  • J Van Cutsem
    • 1
  • U Marusic
    • 3
  • T Torbeyns
    • 1
  • R Meeusen
    • 1
    • 4
    Email author
  1. 1.Research Group Human Physiology, Faculty of Physical Education and Physical TherapyVrije Universiteit BrusselBrusselsBelgium
  2. 2.Fund for Scientific Research Flanders (FWO)BrusselsBelgium
  3. 3.Institute for Kinesiology Research, Science and Research Centre of KoperUniversity of PrimorskaKoperSlovenia
  4. 4.School of Public Health, Tropical Medicine and Rehabilitation SciencesJames Cook UniversityTownsville CityAustralia

Personalised recommendations