Skip to main content
Log in

Modulation of locus coeruleus activity by novel oddball stimuli

  • Brief Communication
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  • Ashburner, J., & Friston, K. J. (1999). Nonlinear spatial normalization using basis functions. Human Brain Mapping, 7, 254–266.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

  • 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.

    Article  Google Scholar 

  • Cloninger, C. R. (1987). A systematic method for clinical description and classification of personality variants. A proposal. Archives of General Psychiatry, 44, 573–588.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Friston, K. J., Josephs, O., Rees, G., & Turner, R. (1998). Nonlinear event-related responses in fMRI. Magnetic Resonance in Medicine, 39, 41–52.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Henson, R. N. A., & Rugg, M. D. (2003). Neural response suppression, haemodynamic repetition effects, and behavioural priming. Neuropsychologia, 41, 263–270.

    Article  CAS  PubMed  Google Scholar 

  • Kamp, S. M., & Donchin, E. (2015). ERP and pupil responses to deviance in an oddball paradigm. Psychophysiology, 52, 460–471.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Kriegeskorte, N., & Bandettini, P. (2007). Analyzing for information, not activation, to exploit high-resolution fMRI. NeuroImage, 38, 649–662.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Lisman, J. E., & Grace, A. A. (2005). The hippocampal-VTA loop: Controlling the entry of information into long-term memory. Neuron, 46, 703–713.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nieuwenhuis, S., Forstmann, B. U., & Wagenmakers, E. J. (2011b). Erroneous analyses of interactions in neuroscience: A problem of significance. Nature Neuroscience, 14, 1105–1107.

    Article  CAS  PubMed  Google Scholar 

  • Nyberg, L. (2005). Any novelty in hippocampal formation and memory? Current Opinion in Neurology, 18, 424–428.

    Article  PubMed  Google Scholar 

  • Ranganath, C., & Rainer, G. (2003). Neural mechanisms for detecting and remembering novel events. Nature Reviews. Neuroscience, 4, 193–202.

    Article  CAS  PubMed  Google Scholar 

  • Rorden, C., & Brett, M. (2000). Stereotaxic display of brain lesions. Behavioural Neurology, 12, 191–200.

    Article  PubMed  Google Scholar 

  • Sara, S. J. (2009). The locus coeruleus and noradrenergic modulation of cognition. Nature Reviews. Neuroscience, 10, 211–223.

    Article  CAS  PubMed  Google Scholar 

  • Sara, S. J. (2015). Locus coeruleus in time with the making of memories. Current Opinion in Neurobiology, 35, 87–94.

    Article  CAS  PubMed  Google Scholar 

  • Sara, S. J., & Bouret, S. (2012). Orienting and reorienting: The locus coeruleus mediates cognition through arousal. Neuron, 76, 130–141.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruth M. Krebs.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krebs, R.M., Park, H.R.P., Bombeke, K. et al. Modulation of locus coeruleus activity by novel oddball stimuli. Brain Imaging and Behavior 12, 577–584 (2018). https://doi.org/10.1007/s11682-017-9700-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-017-9700-4

Keywords

Navigation