Brain Networks Underlying Eye’s Pupil Dynamics
Open accessAbstract
Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.
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Pupil diameter was fairly stable at around 6.5-7 mm on average during all fMRI and 1H-fMRS epochs across conditions.
“Pupil diameter, an index of the noradrenergic tone (DiNuzzo et al., 2019), was fairly stable at around 6.5–7 mm on average during all fMRI (Figure 1—figure supplement 2) and 1H-fMRS (Figure 3—figure supplement 2) epochs (one-way ANOVA, p = 0.99 and p = 0.98, for fMRI runs 1 and 2, respectively, and p = 0.98 and p = 0.96 for 1H-fMRS runs 1 and 2, respectively) across conditions (see also Video 1),”
From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as DiNuzzo et al., 2019
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AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages
Cox, R. W. (1996) · Computers and Biomedical Research · doi:10.1006/cbmr.1996.0014 · Cited by 10,913 · see citing works
Functional connectivity in the motor cortex of resting human brain using echo‐planar mri
Biswal, B., Zerrin Yetkin, F., Haughton, V. M., & Hyde, J. S. (1995) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910340409 · Cited by 9,812 · see citing works
<i>The Brain's Default Network</i>: <i>Anatomy, Function, and Relevance to Disease</i>
Buckner, R. L., Andrews‐Hanna, J. R., & Schacter, D. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.011 · Cited by 9,761 · see citing works
Saliency, switching, attention and control: a network model of insula function
Menon, V., & Uddin, L. Q. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0262-0 · Cited by 5,592 · see citing works
Sridharan, D., Levitin, D. J., & Menon, V. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800005105 · Cited by 2,892 · see citing works
The role of the posterior cingulate cortex in cognition and disease
Leech, R., & Sharp, D. J. (2014) · Brain · doi:10.1093/brain/awt162 · Cited by 2,247 · see citing works
The pupil as a measure of emotional arousal and autonomic activation
Bradley, M. M., Miccoli, L., Escrig, M. A., & Lang, P. J. (2008) · Psychophysiology · doi:10.1111/j.1469-8986.2008.00654.x · Cited by 1,919 · see citing works
Joshi, S., Li, Y., Kalwani, R. M., & Gold, J. I. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.028 · Cited by 1,387 · see citing works
The MVGC multivariate Granger causality toolbox: A new approach to Granger-causal inference
Barnett, L., & Seth, A. K. (2013) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2013.10.018 · Cited by 1,046 · see citing works
Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex
Reimer, J., McGinley, M. J., Liu, Y., Rodenkirch, C., Wang, Q., McCormick, D. A., & Tolias, A. S. (2016) · Nature Communications · doi:10.1038/ncomms13289 · Cited by 926 · see citing works
Pupillometry: A Window to the Preconscious?
Laeng, B., Sirois, S., & Gredebäck, G. (2012) · Perspectives on Psychological Science · doi:10.1177/1745691611427305 · Cited by 921 · see citing works
Pupil diameter covaries with BOLD activity in human locus coeruleus
Murphy, P. R., O'Connell, R. G., O'Sullivan, M., Robertson, I. H., & Balsters, J. H. (2014) · Human Brain Mapping · doi:10.1002/hbm.22466 · Cited by 819 · see citing works
Gilzenrat, M. S., Nieuwenhuis, S., Jepma, M., & Cohen, J. D. (2010) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/cabn.10.2.252 · Cited by 798 · see citing works
Rational regulation of learning dynamics by pupil-linked arousal systems
Nassar, M. R., Rumsey, K. M., Wilson, R. C., Parikh, K., Heasly, B., & Gold, J. I. (2012) · Nature Neuroscience · doi:10.1038/nn.3130 · Cited by 722 · see citing works
Pupil fluctuations track fast switching of cortical states during quiet wakefulness
Reimer, J., Froudarakis, E., Cadwell, C. R., Yatsenko, D., Denfield, G. H., & Tolias, A. S. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.033 · Cited by 717 · see citing works
Adaptive gain and the role of the locus coeruleus–norepinephrine system in optimal performance
Aston‐Jones, G., & Cohen, J. D. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20723 · Cited by 630 · see citing works
McDougal, D. H., & Gamlin, P. D. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140014 · Cited by 614 · see citing works
Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI
Kundu, P., Inati, S., Evans, J. W., Luh, W., & Bandettini, P. A. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.12.028 · Cited by 604 · see citing works
When the Brain Loses Its Self: Prefrontal Inactivation during Sensorimotor Processing
Goldberg, I. I., Harel, M., & Malach, R. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.015 · Cited by 593 · see citing works
Alnæs, D., Sneve, M. H., Espeseth, T., Endestad, T., van de Pavert, S. H., & Laeng, B. (2014) · Journal of Vision · doi:10.1167/14.4.1 · Cited by 497 · see citing works
Pupil-linked arousal is driven by decision uncertainty and alters serial choice bias
Urai, A. E., Braun, A., & Donner, T. H. (2017) · Nature Communications · doi:10.1038/ncomms14637 · Cited by 466 · see citing works
Subregions of the human superior frontal gyrus and their connections
Li, W., Qin, W., Liu, H., Fan, L., Wang, J., Jiang, T., & Yu, C. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.04.011 · Cited by 452 · see citing works
Varazzani, C., San‐Galli, A., Gilardeau, S., & Bouret, S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0454-15.2015 · Cited by 446 · see citing works
Jepma, M., & Nieuwenhuis, S. (2010) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2010.21548 · Cited by 442 · see citing works
On the nature of the BOLD fMRI contrast mechanism
Logothetis, N. K., & Pfeuffer, J. (2004) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2004.10.018 · Cited by 420 · see citing works
At the heart of the ventral attention system: The right anterior insula
Eckert, M. A., Menon, V., Walczak, A., Ahlstrom, J., Denslow, S., Horwitz, A., & Dubno, J. R. (2009) · Human Brain Mapping · doi:10.1002/hbm.20688 · Cited by 406 · see citing works
Integrated strategy for improving functional connectivity mapping using multiecho fMRI
Kundu, P., Brenowitz, N. D., Voon, V., Worbe, Y., Vértes, P. E., Inati, S. J., Saad, Z. S., Bandettini, P. A., & Bullmore, E. T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301725110 · Cited by 399 · see citing works
Pupil dilation deconvolution reveals the dynamics of attention at high temporal resolution
Wierda, S. M., van Rijn, H., Taatgen, N., & Martens, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201858109 · Cited by 321 · see citing works
Arousal Effects on Pupil Size, Heart Rate, and Skin Conductance in an Emotional Face Task
Wang, C., Baird, T., Huang, J. C. H., Coutinho, J., Brien, D. C., & Munoz, D. P. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.01029 · Cited by 312 · see citing works
Ma, Y., Shaik, M. A., Kozberg, M. G., Kim, S. H., Portes, J., Timerman, D., & Hillman, E. M. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525369113 · Cited by 308 · see citing works
Stawarczyk, D., Majerus, S., Maquet, P., & D'Argembeau, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016997 · Cited by 305 · see citing works
Neuromodulatory Correlates of Pupil Dilation
Larsen, R. S., & Waters, J. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00021 · Cited by 263 · see citing works
Pupil Diameter Tracks Lapses of Attention
van den Brink, R. L., Murphy, P. R., & Nieuwenhuis, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165274 · Cited by 226 · see citing works
The cholinergic innervation of the human cerebral cortex.
Mesulam, M.-M. (2004) · Progress in Brain Research · doi:10.1016/s0079-6123(03)45004-8 · Cited by 211 · see citing works
Orbitofrontal Cortex Is Required for Optimal Waiting Based on Decision Confidence
Lak, A., Costa, G. M., Romberg, E., Koulakov, A. A., Mainen, Z. F., & Kepecs, A. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.039 · Cited by 209 · see citing works
Tracking the allocation of attention using human pupillary oscillations
Naber, M., Alvarez, G. A., & Nakayama, K. (2013) · Frontiers in Psychology · doi:10.3389/fpsyg.2013.00919 · Cited by 188 · see citing works
Mathôt, S., & der Stigchel, S. V. (2015) · Current Directions in Psychological Science · doi:10.1177/0963721415593725 · Cited by 182 · see citing works
Tracking arousal state and mind wandering with pupillometry
Nash Unsworth, A., & Robison, M. K. (2018) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-018-0594-4 · Cited by 168 · see citing works
(1993) · Medical Entomology and Zoology · Cited by 168 · see citing works
Yeo, S. S., Chang, P. H., & Jang, S. H. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00416 · Cited by 154 · see citing works
Functional Imaging by I0‐ and T2* ‐parameter mapping using multi‐image EPI
Speck, O., & Hennig, J. (1998) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910400210 · Cited by 147 · see citing works
Pupillary Responses as a Biomarker of Early Risk for Alzheimer’s Disease
Granholm, E. L., Panizzon, M. S., Elman, J. A., Jak, A. J., Hauger, R. L., Bondi, M. W., Lyons, M. J., Franz, C. E., & Kremen, W. S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161078 · Cited by 140 · see citing works
Schneider, M., Hathway, P., Leuchs, L., Sämann, P. G., Czisch, M., & Spoormaker, V. I. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.06.011 · Cited by 138 · see citing works
Internal and external attention and the default mode network
Scheibner, H. J., Bogler, C., Gleich, T., Haynes, J.-D., & Bermpohl, F. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.01.044 · Cited by 133 · see citing works
Yellin, D., Berkovich‐Ohana, A., & Malach, R. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.11.034 · Cited by 129 · see citing works
Hong, L., Walz, J. M., & Sajda, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091321 · Cited by 116 · see citing works
Disentangling reward anticipation with simultaneous pupillometry / fMRI
Schneider, M., Leuchs, L., Czisch, M., Sämann, P. G., & Spoormaker, V. I. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.04.078 · Cited by 100 · see citing works
Contribution of acetylcholine to visual cortex plasticity
Gu, Q. (2003) · Neurobiology of Learning and Memory · doi:10.1016/s1074-7427(03)00073-x · Cited by 95 · see citing works
Gili, T., Saxena, N. K., Diukova, A., Murphy, K., Hall, J. E., & Wise, R. G. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3480-12.2013 · Cited by 89 · see citing works
van Kempen, J., Loughnane, G. M., Newman, D. P., Kelly, S. P., Thiele, A., O’Connell, R. G., & Bellgrove, M. A. (2019) · eLife · doi:10.7554/elife.42541 · Cited by 88 · see citing works
Wang, C., McInnis, H., Brien, D. C., Pari, G., & Munoz, D. P. (2015) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2015.11.019 · Cited by 80 · see citing works
Neural correlates of pupil dilation during human fear learning
Leuchs, L., Schneider, M., Czisch, M., & Spoormaker, V. I. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.11.072 · Cited by 78 · see citing works
The impact of luminance on tonic and phasic pupillary responses to sustained cognitive load
Peysakhovich, V., Vachon, F., & Dehais, F. (2016) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2016.12.003 · Cited by 78 · see citing works
Song, A. H., Kucyi, A., Napadow, V., Brown, E. N., Loggia, M. L., & Akeju, O. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0446-17.2017 · Cited by 78 · see citing works
Task-evoked pupil dilation and BOLD variance as indicators of locus coeruleus dysfunction
Elman, J. A., Panizzon, M. S., Hagler, D. J., Eyler, L. T., Granholm, E. L., Fennema‐Notestine, C., Lyons, M. J., McEvoy, L. K., Franz, C. E., Dale, A. M., et al. (2017) · Cortex · doi:10.1016/j.cortex.2017.09.025 · Cited by 76 · see citing works
Kotani, Y., Ohgami, Y., Kuramoto, Y., Tsukamoto, T., Inoue, Y., & Aihara, Y. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.11.032 · Cited by 69 · see citing works
Pupil dilation patterns reflect the contents of consciousness
Kang, O., & Wheatley, T. (2015) · Consciousness and Cognition · doi:10.1016/j.concog.2015.05.001 · Cited by 59 · see citing works
Sadacca, B. F., Wikenheiser, A. M., & Schoenbaum, G. M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.04.017 · Cited by 59 · see citing works
Covert shift of attention modulates the value encoding in the orbitofrontal cortex
Xie, Y., Nie, C., & Yang, T. (2018) · eLife · doi:10.7554/elife.31507 · Cited by 58 · see citing works
Pupil dilation reveals top–down attentional load during spatial monitoring
Lisi, M., Bonato, M., & Zorzi, M. (2015) · Biological Psychology · doi:10.1016/j.biopsycho.2015.10.002 · Cited by 56 · see citing works
Aminihajibashi, S., Hagen, T., Foldal, M. D., Laeng, B., & Espeseth, T. (2019) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2019.03.007 · Cited by 56 · see citing works
Suppression of pupillary unrest by general anesthesia and propofol sedation
Behrends, M., Larson, M. D., Neice, A. E., et al. (2018) · Journal of Clinical Monitoring and Computing · doi:10.1007/s10877-018-0147-y · Cited by 37 · see citing works
Correlation between Pupil Size and Subjective Passage of Time in Non-Human Primates
Suzuki, T. W., Kunimatsu, J., & Tanaka, M. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2533-16.2016 · Cited by 34 · see citing works
Schwalm, M., & Jubal, E. R. (2017) · eNeuro · doi:10.1523/eneuro.0293-16.2017 · Cited by 29 · see citing works
Metastable States of Multiscale Brain Networks Are Keys to Crack the Timing Problem
Gili, T., Ciullo, V., & Spalletta, G. (2018) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2018.00075 · Cited by 9 · see citing works
Foggy windows: Pupillary responses during task preparation
Trani, A. N., & Verhaeghen, P. (2018) · Quarterly Journal of Experimental Psychology · doi:10.1177/1747021817740856 · Cited by 7 · see citing works
Jones (1999) · doi:10.1002/(sici)1522-2594(199907)42:1
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Perception is associated with the brain’s metabolic response to sensory stimulation
DiNuzzo, M., Mangia, S., Moraschi, M., Mascali, D., Hagberg, G. E., & Giove, F. (2022) · eLife · doi:10.7554/elife.71016 · Cited by 25 · see citing works
“…might be an indicator of sensory perception, in keeping with the dynamics of lactate and glutamate across the sleep–wake cycle (Aalling et al., 2018; DiNuzzo and Nedergaard, 2017; Naylor et al., 2012; Naylor et al., 2011) as well as with the relation between lactate and arousal (Zuend et al.,…”
BackgroundSelf-citation
- Authors
- DiNuzzo, M., Mascali, D., Moraschi, M., Bussu, G., Maugeri, L., Mangini, F., Fratini, M., & Giove, F.
- Affiliations
- Fondazione Santa Lucia (IT)
- Centro Ricerche Enrico Fermi (IT)
- Radboud University Nijmegen (NL)
- Istituto di Nanotecnologia (IT)
- Corresponding author
- DiNuzzo, Mauro
- ORCID
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-09-18
- Volume
- 13
- Pages
- 965-965
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC6759985
- OpenAlex
- W2971177595
- Cited by
- 74
- References
- 67
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 12 · 2023: 11 · 2022: 11 · 2021: 14 · 2020: 5 · 2019: 1 · 2018: 1
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Ministero della Salute (GR-2013-02358177)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- pupil dynamics, locus coeruleus, cortical deactivation, functional connectivity, Granger causality, superior frontal gyrus, posterior cingulate cortex, anterior insula, orbitofrontal cortex, attentional load, pupillometry, BOLD fMRI
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