Skip to main content

Cortical interaction of bilateral inputs is similar for noxious and innocuous stimuli but leads to different perceptual effects

Abstract

The cerebral integration of somatosensory inputs from multiple sources is essential to produce adapted behaviors. Previous studies suggest that bilateral somatosensory inputs interact differently depending on stimulus characteristics, including their noxious nature. The aim of this study was to clarify how bilateral inputs evoked by noxious laser stimuli, noxious shocks, and innocuous shocks interact in terms of perception and brain responses. The experiment comprised two conditions (right-hand stimulation and concurrent stimulation of both hands) in which painful laser stimuli, painful shocks and non-painful shocks were delivered. Perception, somatosensory-evoked potentials (P45, N100, P260), laser-evoked potentials (N1, N2 and P2) and event-related spectral perturbations (delta to gamma oscillation power) were compared between conditions and stimulus modalities. The amplitude of negative vertex potentials (N2 or N100) and the power of delta/theta oscillations were increased in the bilateral compared with unilateral condition, regardless of the stimulus type (P < 0.01). However, gamma oscillation power increased for painful and non-painful shocks (P < 0.01), but not for painful laser stimuli (P = 0.08). Despite the similarities in terms of brain activity, bilateral inputs interacted differently for painful stimuli, for which perception remained unchanged, and non-painful stimuli, for which perception increased. This may reflect a ceiling effect for the attentional capture by noxious stimuli and warrants further investigations to examine the regulation of such interactions by bottom–up and top–down processes.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Availability of data and material

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

Code availability

The custom code generated for the current study are available from the corresponding author on reasonable request.

Abbreviations

ERP:

Event-related potentials

LEP:

Laser-evoked potentials

ERSP:

Event-related spectral perturbations

EEG:

Electroencephalography

References

  1. Allison T, McCarthy G, Luby M, Puce A, Spencer DD (1996) Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation. Electroencephalogr Clin Neurophysiol 100(2):126–140. https://doi.org/10.1016/0013-4694(95)00226-x

    CAS  Article  PubMed  Google Scholar 

  2. Beume LA, Kaller CP, Hoeren M, Kloppel S, Kuemmerer D, Glauche V, Umarova R et al (2015) Processing of bilateral versus unilateral conditions: evidence for the functional contribution of the ventral attention network. Cortex 66:91–102. https://doi.org/10.1016/j.cortex.2015.02.018

    Article  PubMed  Google Scholar 

  3. Bidet-Caulet A, Fischer C, Bauchet F, Aguera PE, Bertrand O (2007a) Neural substrate of concurrent sound perception: direct electrophysiological recordings from human auditory cortex. Front Hum Neurosci 1:5. https://doi.org/10.3389/neuro.09.005.2007

    Article  PubMed  Google Scholar 

  4. Bidet-Caulet A, Fischer C, Besle J, Aguera PE, Giard MH, Bertrand O (2007b) Effects of selective attention on the electrophysiological representation of concurrent sounds in the human auditory cortex. J Neurosci 27(35):9252–9261. https://doi.org/10.1523/jneurosci.1402-07.2007

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Chien JH, Liu CC, Kim JH, Markman TM, Lenz FA (2014) Painful cutaneous laser stimuli induce event-related oscillatory EEG activities that are different from those induced by nonpainful electrical stimuli. J Neurophysiol 112(4):824–833. https://doi.org/10.1152/jn.00209.2014

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. D’Amour S, Harris LR (2014) Contralateral tactile masking between forearms. Exp Brain Res 232(3):821–826. https://doi.org/10.1007/s00221-013-3791-y

    Article  PubMed  Google Scholar 

  7. D’Amour S, Harris LR (2016) Testing tactile masking between the forearms. J vis Exp 108:e53733. https://doi.org/10.3791/53733

    Article  Google Scholar 

  8. Defrin R, Tsedek I, Lugasi I, Moriles I, Urca G (2010) The interactions between spatial summation and DNIC: effect of the distance between two painful stimuli and attentional factors on pain perception. Pain 151(2):489–495. https://doi.org/10.1016/j.pain.2010.08.009

    Article  PubMed  Google Scholar 

  9. Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134(1):9–21. https://doi.org/10.1016/j.jneumeth.2003.10.009

    Article  Google Scholar 

  10. Dowman R (1994a) SEP topographies elicited by innocuous and noxious sural nerve stimulation. I. Identification of stable periods and individual differences. Electroencephalogr Clin Neurophysiol Evoked Potentials Sect 92(4):291–302. https://doi.org/10.1016/0168-5597(94)90097-3

    CAS  Article  Google Scholar 

  11. Dowman R (1994b) SEP topographies elicited by innocuous and noxious sural nerve stimulation. II. Effects of stimulus intensity on topographic pattern and amplitude. Electroencephalogr Clin Neurophysiol 92(4):303–315. https://doi.org/10.1016/0168-5597(94)90098-1

    CAS  Article  PubMed  Google Scholar 

  12. Dowman R (2004) Topographic analysis of painful laser and sural nerve electrical evoked potentials. Brain Topogr 16(3):169–179. https://doi.org/10.1023/b:brat.0000019185.30489.ad

    Article  PubMed  Google Scholar 

  13. Fries P (2009) Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu Rev Neurosci 32(1):209–224. https://doi.org/10.1146/annurev.neuro.051508.135603

    CAS  Article  PubMed  Google Scholar 

  14. Fries P (2015) Rhythms for cognition: communication through coherence. Neuron 88(1):220–235. https://doi.org/10.1016/j.neuron.2015.09.034

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Garcia-Larrea L (2006) Chapter 30 Evoked potentials in the assessment of pain. In: Cervero F, Jensen TS (eds) Handb clin neurol, vol 81. Elsevier, p 439-XI

  16. Girard S, Pelland M, Lepore F, Collignon O (2013) Impact of the spatial congruence of redundant targets on within-modal and cross-modal integration. Exp Brain Res 224(2):275–285. https://doi.org/10.1007/s00221-012-3308-0

    CAS  Article  PubMed  Google Scholar 

  17. Gross J, Schnitzler A, Timmermann L, Ploner M (2007) Gamma oscillations in human primary somatosensory cortex reflect pain perception. PLoS Biol 5(5):e133. https://doi.org/10.1371/journal.pbio.0050133

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Harris JA, Arabzadeh E, Fairhall AL, Benito C, Diamond ME (2006) Factors affecting frequency discrimination of vibrotactile stimuli: implications for cortical encoding. PLoS ONE 1:e100. https://doi.org/10.1371/journal.pone.0000100

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hauck M, Domnick C, Lorenz J, Gerloff C, Engel AK (2015) Top-down and bottom-up modulation of pain-induced oscillations. Front Hum Neurosci 9:375. https://doi.org/10.3389/fnhum.2015.00375

    Article  PubMed  PubMed Central  Google Scholar 

  20. Heid C, Mouraux A, Treede RD, Schuh-Hofer S, Rupp A, Baumgärtner U (2020) Early gamma-oscillations as correlate of localized nociceptive processing in primary sensorimotor cortex. J Neurophysiol 123(5):1711–1726. https://doi.org/10.1152/jn.00444.2019

    CAS  Article  PubMed  Google Scholar 

  21. Hoechstetter K, Rupp A, Stančák A, Meinck H-M, Stippich C, Berg P, Scherg M (2001) Interaction of tactile input in the human primary and secondary somatosensory cortex—a magnetoencephalographic study. Neuroimage 14(3):759–767. https://doi.org/10.1006/nimg.2001.0855

    CAS  Article  PubMed  Google Scholar 

  22. Iannetti GD, Hughes NP, Lee MC, Mouraux A (2008) Determinants of laser-evoked EEG responses: pain perception or stimulus saliency? J Neurophysiol 100(2):815–828. https://doi.org/10.1152/jn.00097.2008

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Kakigi R, Jones SJ (1986) Influence of concurrent tactile stimulation on somatosensory evoked potentials following posterior tibial nerve stimulation in man. Electroencephalogr Clin Neurophysiol 65(2):118–129. https://doi.org/10.1016/0168-5597(86)90044-4

    CAS  Article  PubMed  Google Scholar 

  24. Kennett S, Taylor-Clarke M, Haggard P (2001) Noninformative vision improves the spatial resolution of touch in humans. Curr Biol 11(15):1188–1191. https://doi.org/10.1016/s0960-9822(01)00327-x

    CAS  Article  PubMed  Google Scholar 

  25. Kuroki S, Watanabe J, Nishida S (2017) Integration of vibrotactile frequency information beyond the mechanoreceptor channel and somatotopy. Sci Rep 7(1):2758. https://doi.org/10.1038/s41598-017-02922-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Lautenbacher S, Prager M, Rollman GB (2007) Pain additivity, diffuse noxious inhibitory controls, and attention: a functional measurement analysis. Somatosens Mot Res 24(4):189–201. https://doi.org/10.1080/08990220701637638

    Article  PubMed  Google Scholar 

  27. Le Bars D, Dickenson AH, Besson JM (1979) Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 6(3):283–304

    Article  Google Scholar 

  28. Lee MC, Mouraux A, Iannetti GD (2009) Characterizing the cortical activity through which pain emerges from nociception. J Neurosci 29(24):7909–7916. https://doi.org/10.1523/jneurosci.0014-09.2009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Legrain V, Iannetti GD, Plaghki L, Mouraux A (2011) The pain matrix reloaded: a salience detection system for the body. Prog Neurobiol 93(1):111–124. https://doi.org/10.1016/j.pneurobio.2010.10.005

    Article  PubMed  Google Scholar 

  30. Liu Z, Zhang N, Chen W, He B (2009) Mapping the bilateral visual integration by EEG and fMRI. Neuroimage 46(4):989–997. https://doi.org/10.1016/j.neuroimage.2009.03.028

    Article  PubMed  Google Scholar 

  31. Madden VJ, Catley MJ, Grabherr L, Mazzola F, Shohag M, Moseley GL (2016) The effect of repeated laser stimuli to ink-marked skin on skin temperature—recommendations for a safe experimental protocol in humans. PeerJ. https://doi.org/10.7717/peerj.1577

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mejias JF, Murray JD, Kennedy H, Wang X-J (2016) Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex. Sci Adv 2(11):e1601335. https://doi.org/10.1126/sciadv.1601335

    Article  PubMed  PubMed Central  Google Scholar 

  33. Moayedi M, Liang M, Sim AL, Hu L, Haggard P, Iannetti GD (2015) Laser-evoked vertex potentials predict defensive motor actions. Cereb Cortex 25(12):4789–4798. https://doi.org/10.1093/cercor/bhv149

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Moayedi M, Di Stefano G, Stubbs MT, Djeugam B, Liang M, Iannetti GD (2016) Nociceptive-evoked potentials are sensitive to behaviorally relevant stimulus displacements in egocentric coordinates. eNeuro. https://doi.org/10.1523/eneuro.0151-15.2016

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mouraux A, Iannetti GD (2008) Across-trial averaging of event-related EEG responses and beyond. Magn Reson Imaging 26(7):1041–1054. https://doi.org/10.1016/j.mri.2008.01.011

    CAS  Article  PubMed  Google Scholar 

  36. Nielsen J, Arendt-Nielsen L (1997) Spatial summation of heat induced pain within and between dermatomes. Somatosens Mot Res 14(2):119–125. https://doi.org/10.1080/08990229771123

    CAS  Article  PubMed  Google Scholar 

  37. Northon S, Rustamov N, Piche M (2019) Cortical integration of bilateral nociceptive signals: when more is less. Pain 160(3):724–733. https://doi.org/10.1097/j.pain.0000000000001451

    Article  PubMed  Google Scholar 

  38. Perchet C, Godinho F, Mazza S, Frot M, Legrain V, Magnin M, Garcia-Larrea L (2008) Evoked potentials to nociceptive stimuli delivered by CO2 or Nd:YAP lasers. Clin Neurophysiol 119(11):2615–2622. https://doi.org/10.1016/j.clinph.2008.06.021

    Article  PubMed  Google Scholar 

  39. Plaghki L, Mouraux A (2003) How do we selectively activate skin nociceptors with a high power infrared laser? Physiology and biophysics of laser stimulation. Neurophysiol Clin 33(6):269–277

    CAS  Article  Google Scholar 

  40. Ploner M, Sorg C, Gross J (2017) Brain rhythms of pain. Trends Cogn Sci 21(2):100–110. https://doi.org/10.1016/j.tics.2016.12.001

    Article  PubMed  PubMed Central  Google Scholar 

  41. Quevedo AS, Coghill RC (2007) Attentional modulation of spatial integration of pain: evidence for dynamic spatial tuning. J Neurosci 27(43):11635–11640. https://doi.org/10.1523/jneurosci.3356-07.2007

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Ragert P, Nierhaus T, Cohen LG, Villringer A (2011) Interhemispheric interactions between the human primary somatosensory cortices. PLoS ONE. https://doi.org/10.1371/journal.pone.0016150

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ronga I, Valentini E, Mouraux A, Iannetti GD (2013) Novelty is not enough: laser-evoked potentials are determined by stimulus saliency, not absolute novelty. J Neurophysiol 109(3):692–701. https://doi.org/10.1152/jn.00464.2012

    CAS  Article  PubMed  Google Scholar 

  44. Rossiter HE, Worthen SF, Witton C, Hall SD, Furlong PL (2013) Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory cortex. Front Hum Neurosci 7:362. https://doi.org/10.3389/fnhum.2013.00362

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Rustamov N, Northon S, Tessier J, Leblond H, Piche M (2019) Integration of bilateral nociceptive inputs tunes spinal and cerebral responses. Sci Rep 9(1):7143. https://doi.org/10.1038/s41598-019-43567-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. Saija JD, Başkent D, Andringa TC, Akyürek EG (2017) Visual and auditory temporal integration in healthy younger and older adults. Psychol Res. https://doi.org/10.1007/s00426-017-0912-4

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sambo CF, Forster B, Williams SC, Iannetti GD (2012) To blink or not to blink: fine cognitive tuning of the defensive peripersonal space. J Neurosci 32(37):12921–12927. https://doi.org/10.1523/jneurosci.0607-12.2012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. Sandrini G, Serrao M, Rossi P, Romaniello A, Cruccu G, Willer JC (2005) The lower limb flexion reflex in humans. Prog Neurobiol 77(6):353–395. https://doi.org/10.1016/j.pneurobio.2005.11.003

    Article  PubMed  Google Scholar 

  49. Schnitzler A, Gross J (2005) Normal and pathological oscillatory communication in the brain. Nat Rev Neurosci 6(4):285–296. https://doi.org/10.1038/nrn1650

    CAS  Article  PubMed  Google Scholar 

  50. Schulz E, Tiemann L, Witkovsky V, Schmidt P, Ploner M (2012) gamma Oscillations are involved in the sensorimotor transformation of pain. J Neurophysiol 108(4):1025–1031. https://doi.org/10.1152/jn.00186.2012

    Article  PubMed  Google Scholar 

  51. Sherrington CS (1906) The integrative action of the nervous system. Yale University Press, New Haven

    Google Scholar 

  52. Sherrington CS (1910) Flexion-reflex of the limb, crossed extension-reflex, and reflex stepping and standing. J Physiol 40(1–2):28–121. https://doi.org/10.1113/jphysiol.1910.sp001362

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. Simões C, Alary F, Forss N, Hari R (2002) Left-hemisphere-dominant SII activation after bilateral median nerve stimulation. Neuroimage 15(3):686–690. https://doi.org/10.1006/nimg.2001.1007

    Article  PubMed  Google Scholar 

  54. Tabor A, Thacker MA, Moseley GL, Körding KP (2017) Pain: a statistical account. PLoS Comput Biol 13(1):e1005142. https://doi.org/10.1371/journal.pcbi.1005142

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. Tame L, Pavani F, Papadelis C, Farne A, Braun C (2015) Early integration of bilateral touch in the primary somatosensory cortex. Hum Brain Mapp 36(4):1506–1523. https://doi.org/10.1002/hbm.22719

    Article  PubMed  Google Scholar 

  56. Tan LL, Oswald MJ, Heinl C, Retana Romero OA, Kaushalya SK, Monyer H, Kuner R (2019) Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception. Nat Commun 10(1):983. https://doi.org/10.1038/s41467-019-08873-z

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. Tiemann L, Schulz E, Gross J, Ploner M (2010) Gamma oscillations as a neuronal correlate of the attentional effects of pain. Pain 150(2):302–308. https://doi.org/10.1016/j.pain.2010.05.014

    Article  PubMed  Google Scholar 

  58. Tiemann L, May ES, Postorino M, Schulz E, Nickel MM, Bingel U, Ploner M (2015) Differential neurophysiological correlates of bottom-up and top-down modulations of pain. Pain 156(2):289–296. https://doi.org/10.1097/01.j.pain.0000460309.94442.44

    Article  PubMed  Google Scholar 

  59. Torta DM, Liang M, Valentini E, Mouraux A, Iannetti GD (2012) Dishabituation of laser-evoked EEG responses: dissecting the effect of certain and uncertain changes in stimulus spatial location. Exp Brain Res 218(3):361–372. https://doi.org/10.1007/s00221-012-3019-6

    CAS  Article  PubMed  Google Scholar 

  60. Torta DM, Legrain V, Mouraux A (2015) Looking at the hand modulates the brain responses to nociceptive and non-nociceptive somatosensory stimuli but does not necessarily modulate their perception. Psychophysiology 52(8):1010–1018. https://doi.org/10.1111/psyp.12439

    Article  PubMed  PubMed Central  Google Scholar 

  61. Valentini E, Betti V, Hu L, Aglioti SM (2013) Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli. Cortex 49(2):446–462. https://doi.org/10.1016/j.cortex.2012.02.005

    Article  PubMed  Google Scholar 

  62. Willer JC (1977) Comparative study of perceived pain and nociceptive flexion reflex in man. Pain 3(1):69–80. https://doi.org/10.1016/0304-3959(77)90036-7

    Article  PubMed  Google Scholar 

  63. Woolf CJ, Ma Q (2007) Nociceptors—noxious stimulus detectors. Neuron 55(3):353–364. https://doi.org/10.1016/j.neuron.2007.07.016

    CAS  Article  PubMed  Google Scholar 

  64. Yarnitsky D (2010) Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 23(5):611–615. https://doi.org/10.1097/ACO.0b013e32833c348b

    Article  PubMed  Google Scholar 

  65. Yue L, Iannetti GD, Hu L (2020) The neural origin of nociceptive-induced gamma-band oscillations. J Neurosci 40(17):3478–3490. https://doi.org/10.1523/jneurosci.0255-20.2020

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. Zhang ZG, Hu L, Hung YS, Mouraux A, Iannetti GD (2012) Gamma-band oscillations in the primary somatosensory cortex—a direct and obligatory correlate of subjective pain intensity. J Neurosci 32(22):7429–7438. https://doi.org/10.1523/jneurosci.5877-11.2012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Natural Science and Engineering Research Council of Canada (#06659) and the Canadian Foundation for Innovation (#33731). The contribution of Stéphane Northon was supported by the Fonds de Recherche du Québec en Nature et Technologie. The contribution of Zoha Deldar was supported by the Department of Anatomy of the Université du Québec à Trois-Rivières and the Centre de recherche en Neuropsychologie et Cognition. The contribution of Mathieu Piché was supported by the Fonds de Recherche du Québec en Santé.

Funding

This work was supported by a grant from the Natural Science and Engineering Research Council of Canada (#06659) and the Canadian Foundation for Innovation (#33731). The contribution of Stéphane Northon was supported by the Fonds de Recherche du Québec en Nature et Technologie. The contribution of Zoha Deldar was supported by the Department of Anatomy of the Université du Québec à Trois-Rivières and the Centre de recherche en Neuropsychologie et Cognition. The contribution of Mathieu Piché was supported by the Fonds de Recherche du Québec en Santé.

Author information

Affiliations

Authors

Contributions

All authors contributed significantly to this study and has read the final version of the manuscript. SN contributed to data collection and analyses and wrote the first version of the manuscript. ZD contributed to data collection. MP contributed to study design, data collection, analyses and interpretation, wrote the final version of the manuscript and obtained funding.

Corresponding author

Correspondence to Mathieu Piché.

Ethics declarations

Conflict of interests

The authors declare that they have no competing interests.

Ethics approval

All experimental procedures conformed to the standards set by the latest revision of the Declaration of Helsinki and were approved by the Research Ethics Board of the Université du Québec à Trois-Rivières.

Consent to participate

All participants received written informed consent, acknowledged their right to withdraw from the experiment without prejudice, and received a compensation of $25 for their time.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Communicated by Melvyn A. Goodale.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1366 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Northon, S., Deldar, Z. & Piché, M. Cortical interaction of bilateral inputs is similar for noxious and innocuous stimuli but leads to different perceptual effects. Exp Brain Res 239, 2803–2819 (2021). https://doi.org/10.1007/s00221-021-06175-9

Download citation

Keywords

  • Pain
  • Bilateral
  • Nociception
  • Electroencephalography
  • Saliency
  • Integration