Advertisement

Brain Imaging and Behavior

, Volume 12, Issue 2, pp 577–584 | Cite as

Modulation of locus coeruleus activity by novel oddball stimuli

  • Ruth M. Krebs
  • Haeme R. P. Park
  • Klaas Bombeke
  • Carsten N. Boehler
Brief Communication

Abstract

It has long been known from animal literature that the locus coeruleus (LC), the source region of noradrenergic neurons in the brain, is sensitive to unexpected, novel, and other salient events. In humans, however, direct assessment of LC activity has proven to be challenging due to its small size and difficult localization, which is why noradrenergic activity has often been assessed using more indirect measures such as electroencephalography (EEG) and pupil recordings. Here, we combined high-resolution functional magnetic resonance imaging (fMRI) with a special anatomical sequence to assess neural activity in the LC in response to different types of salient stimuli in an oddball paradigm (novel neutral oddballs, novel emotional oddballs, and familiar target oddballs). We found a significant linear increase of LC activity from standard trials, over familiar target oddballs, to novel neutral and novel emotional oddballs. Importantly, when breaking down this linear trend, only novel oddball stimuli led to robust activity increases as compared to standard trials, with no statistical difference between neutral and emotional ones. This pattern suggests that activity modulations in the LC in the present study were mainly driven by stimulus novelty, rather than by emotional saliency, task relevance, or contextual novelty alone. Moreover, the absence of significant activity modulations in response to target oddballs (which were reported in a recent study) suggests that the LC represents relative rather than absolute saliency of a stimulus in its respective context.

Keywords

Locus coeruleus fMRI Oddball Novelty Saliency 

Notes

Compliance with ethical standards

Funding

This study was supported by a postdoctoral research grant of the Research Foundation Flanders (grant No. FWO11/PDO/016 awarded to RMK) and a starting grant of the European Research Council (ERC) under the Horizon 2020 framework (grant No. 636110 awarded to RMK).

Conflict of interest

Ruth M. Krebs, Haeme R. P. Park, K. Bombeke, and Carsten N. Boehler declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. Ashburner, J., & Friston, K. J. (1999). Nonlinear spatial normalization using basis functions. Human Brain Mapping, 7, 254–266.CrossRefPubMedGoogle Scholar
  2. Astafiev, S. V., Snyder, A. Z., Shulman, G. L., & Corbetta, M. (2010). Comment on "Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI" and "homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area". Science, 328, 309.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Aston-Jones, G., Chiang, C., & Alexinsky, T. (1991). Discharge of noradrenergic locus coeruleus neurons in behaving rats and monkeys suggests a role in vigilance. Progress in Brain Research, 88, 501–520.CrossRefPubMedGoogle Scholar
  4. Aston-Jones, G., & Cohen, J. D. (2005). An integrative theory of locus coeruleus-norepinephrine function: Adaptive gain and optimal performance. Annual Review of Neuroscience, 28, 403–450.CrossRefPubMedGoogle Scholar
  5. Berridge, C. W., & Waterhouse, B. D. (2003). The locus coeruleus-noradrenergic system: Modulation of behavioral state and state-dependent cognitive processes. Brain Research. Brain Research Reviews, 42, 33–84.CrossRefPubMedGoogle Scholar
  6. Bouret, S., Ravel, S., & Richmond, B. J. (2012). Complementary neural correlates of motivation in dopaminergic and noradrenergic neurons of monkeys. Frontiers in Behavioral Neuroscience, 6, 40.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bradley, M. M., Miccoli, L., Escrig, M. A., & Lang, P. J. (2008). The pupil as a measure of emotional arousal and autonomic activation. Psychophysiology, 45, 602–607.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Brett, M., Anton, J.-L., Valabregue, R., & Poline, J.-P. (2002). Region of interest analysis using an SPM toolbox (abstract). Available on CD-Rom. Neuroimage, 16.Google Scholar
  9. Carver, C. S., & White, T. L. (1994). Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS scales. Journal of Personality and Social Psychology, 67, 319–333.CrossRefGoogle Scholar
  10. Cloninger, C. R. (1987). A systematic method for clinical description and classification of personality variants. A proposal. Archives of General Psychiatry, 44, 573–588.CrossRefPubMedGoogle Scholar
  11. Dien, J., Spencer, K. M., & Donchin, E. (2003). Localization of the event-related potential novelty response as defined by principal components analysis. Brain Research. Cognitive Brain Research, 17, 637–650.CrossRefPubMedGoogle Scholar
  12. Fernandes, P., Regala, J., Correia, F., & Goncalves-Ferreira, A. J. (2012). The human locus coeruleus 3-D stereotactic anatomy. Surgical and Radiologic Anatomy, 34, 879–885.CrossRefPubMedGoogle Scholar
  13. Fichtenholtz, H. M., Dean, H. L., Dillon, D. G., Yamasaki, H., McCarthy, G., & LaBar, K. S. (2004). Emotion-attention network interactions during a visual oddball task. Brain Research. Cognitive Brain Research, 20, 67–80.CrossRefPubMedGoogle Scholar
  14. Friston, K. J., Josephs, O., Rees, G., & Turner, R. (1998). Nonlinear event-related responses in fMRI. Magnetic Resonance in Medicine, 39, 41–52.CrossRefPubMedGoogle Scholar
  15. Grant, S. J., Aston-Jones, G., & Redmond Jr., D. E. (1988). Responses of primate locus coeruleus neurons to simple and complex sensory stimuli. Brain Research Bulletin, 21, 401–410.CrossRefPubMedGoogle Scholar
  16. Harvey, A. K., Pattinson, K. T., Brooks, J. C., Mayhew, S. D., Jenkinson, M., & Wise, R. G. (2008). Brainstem functional magnetic resonance imaging: Disentangling signal from physiological noise. Journal of Magnetic Resonance Imaging, 28, 1337–1344.CrossRefPubMedGoogle Scholar
  17. Henson, R. N. A., & Rugg, M. D. (2003). Neural response suppression, haemodynamic repetition effects, and behavioural priming. Neuropsychologia, 41, 263–270.CrossRefPubMedGoogle Scholar
  18. Kamp, S. M., & Donchin, E. (2015). ERP and pupil responses to deviance in an oddball paradigm. Psychophysiology, 52, 460–471.CrossRefPubMedGoogle Scholar
  19. Keren, N. I., Lozar, C. T., Harris, K. C., Morgan, P. S., & Eckert, M. A. (2009). In vivo mapping of the human locus coeruleus. NeuroImage, 47, 1261–1267.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kohler, S., Bar, K. J., & Wagner, G. (2016). Differential involvement of brainstem noradrenergic and midbrain dopaminergic nuclei in cognitive control. Human Brain Mapping, 37, 2305–2318.CrossRefPubMedGoogle Scholar
  21. Krebs, R. M., Fias, W., Achten, E., & Boehler, C. N. (2013). Picture novelty attenuates semantic interference and modulates concomitant neural activity in the anterior cingulate cortex and the locus coeruleus. NeuroImage, 74, 179–187.CrossRefPubMedGoogle Scholar
  22. Kriegeskorte, N., & Bandettini, P. (2007). Analyzing for information, not activation, to exploit high-resolution fMRI. NeuroImage, 38, 649–662.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Kriegeskorte, N., Simmons, W. K., Bellgowan, P. S., & Baker, C. I. (2009). Circular analysis in systems neuroscience: The dangers of double dipping. Nature Neuroscience, 12, 535–540.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Langner, O., Dotsch, R., Bijlstra, G., Wigboldus, D. H. J., Hawk, S. T., & van Knippenberg, A. (2010). Presentation and validation of the Radboud faces database. Cognition & Emotion, 24, 1377–1388.CrossRefGoogle Scholar
  25. Liddell, B. J., Brown, K. J., Kemp, A. H., Barton, M. J., Das, P., Peduto, A., Gordon, E., & Williams, L. M. (2005). A direct brainstem-amygdala-cortical 'alarm' system for subliminal signals of fear. NeuroImage, 24, 235–243.CrossRefPubMedGoogle Scholar
  26. Limbrick-Oldfield, E. H., Brooks, J. C., Wise, R. J., Padormo, F., Hajnal, J. V., Beckmann, C. F., & Ungless, M. A. (2011). Identification and characterisation of midbrain nuclei using optimised functional magnetic resonance imaging. NeuroImage, 59, 1230–1238.CrossRefPubMedGoogle Scholar
  27. Lisman, J. E., & Grace, A. A. (2005). The hippocampal-VTA loop: Controlling the entry of information into long-term memory. Neuron, 46, 703–713.CrossRefPubMedGoogle Scholar
  28. Murphy, P. R., O'Connell, R. G., O'Sullivan, M., Robertson, I. H., & Balsters, J. H. (2014). Pupil diameter covaries with BOLD activity in human locus coeruleus. Human Brain Mapping, 35, 4140–4154.CrossRefPubMedGoogle Scholar
  29. Nieuwenhuis, S., De Geus, E. J., & Aston-Jones, G. (2011a). The anatomical and functional relationship between the P3 and autonomic components of the orienting response. Psychophysiology, 48, 162–175.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Nieuwenhuis, S., Forstmann, B. U., & Wagenmakers, E. J. (2011b). Erroneous analyses of interactions in neuroscience: A problem of significance. Nature Neuroscience, 14, 1105–1107.CrossRefPubMedGoogle Scholar
  31. Nyberg, L. (2005). Any novelty in hippocampal formation and memory? Current Opinion in Neurology, 18, 424–428.CrossRefPubMedGoogle Scholar
  32. Ranganath, C., & Rainer, G. (2003). Neural mechanisms for detecting and remembering novel events. Nature Reviews. Neuroscience, 4, 193–202.CrossRefPubMedGoogle Scholar
  33. Rorden, C., & Brett, M. (2000). Stereotaxic display of brain lesions. Behavioural Neurology, 12, 191–200.CrossRefPubMedGoogle Scholar
  34. Sara, S. J. (2009). The locus coeruleus and noradrenergic modulation of cognition. Nature Reviews. Neuroscience, 10, 211–223.CrossRefPubMedGoogle Scholar
  35. Sara, S. J. (2015). Locus coeruleus in time with the making of memories. Current Opinion in Neurobiology, 35, 87–94.CrossRefPubMedGoogle Scholar
  36. Sara, S. J., & Bouret, S. (2012). Orienting and reorienting: The locus coeruleus mediates cognition through arousal. Neuron, 76, 130–141.CrossRefPubMedGoogle Scholar
  37. Sara, S. J., Dyon-Laurent, C., & Herve, A. (1995). Novelty seeking behavior in the rat is dependent upon the integrity of the noradrenergic system. Brain Research. Cognitive Brain Research, 2, 181–187.CrossRefPubMedGoogle Scholar
  38. Snowden, R. J., O'Farrell, K. R., Burley, D., Erichsen, J. T., Newton, N. V., & Gray, N. S. (2016). The pupil's response to affective pictures: Role of image duration, habituation, and viewing mode. Psychophysiology, 53, 1217–1223.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Sterpenich, V., D'Argembeau, A., Desseilles, M., Balteau, E., Albouy, G., Vandewalle, G., Degueldre, C., Luxen, A., Collette, F., & Maquet, P. (2006). The locus ceruleus is involved in the successful retrieval of emotional memories in humans. The Journal of Neuroscience, 26, 7416–7423.CrossRefPubMedGoogle Scholar
  40. Zheng, Y., Xu, J., Jin, Y., Sheng, W., Ma, Y., Zhang, X., & Shen, H. (2010). The time course of novelty processing in sensation seeking: An ERP study. International Journal of Psychophysiology, 76, 57–63.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Ruth M. Krebs
    • 1
  • Haeme R. P. Park
    • 1
  • Klaas Bombeke
    • 1
  • Carsten N. Boehler
    • 1
  1. 1.Department of Experimental PsychologyGhent UniversityGhentBelgium

Personalised recommendations