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Pupil diameter covaries with BOLD activity in human locus coeruleus
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The locus coeruleus-noradrenergic (LC-NA) neuromodulatory system has been implicated in a broad array of cognitive processes, yet scope for investigating this system's function in humans is currently limited by an absence of reliable non-invasive measures of LC activity. Although pupil diameter has been employed as a proxy measure of LC activity in numerous studies, empirical evidence for a relationship between the two is lacking. In the present study, we sought to rigorously probe the relationship between pupil diameter and BOLD activity localized to the human LC. Simultaneous pupillometry and fMRI revealed a relationship between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC, as localized via neuromelanin-sensitive structural imaging and an LC atlas. This relationship was present both at rest and during performance of a two-stimulus oddball task, with and without spatial smoothing of the fMRI data, and survived retrospective image correction for physiological noise. Furthermore, the spatial extent of this pupil/LC relationship guided a volume-of-interest analysis in which we provide the first demonstration in humans of a fundamental characteristic of animal LC activity: phasic modulation by oddball stimulus relevance. Taken together, these findings highlight the potential for utilizing pupil diameter to achieve a more comprehensive understanding of the role of the LC-NA system in human cognition.
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“studies have shown a direct correlation between slow fluctuations in LC activity and pupil size (Rajkowski, 1993;Murphy et al., 2014).”
From Is autonomic nervous system function atypical in Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the evidence (2020) · cites this paper as Murphy et al., 2014
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Metadata
- Authors
- Murphy, P. R., O'Connell, R. G., O'Sullivan, M., Robertson, I. H., & Balsters, J. H.
- Affiliations
- Trinity College Dublin (IE)
- Trinity College Institute of Neuroscience and School of Psychology Trinity College Dublin Dublin 2 Ireland
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2014-02-07
- Volume
- 35
- Issue
- 8
- Pages
- 4140-4154
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6869043
- OpenAlex
- W1601100579
- Cited by
- 819
- References
- 77
- Citations by year
- 2026: 77 · 2025: 71 · 2024: 83 · 2023: 81 · 2022: 83 · 2021: 85 · 2020: 79 · 2019: 64 · 2018: 60 · 2017: 56 · 2016: 48 · 2015: 24 · 2014: 8
- FWCI
- 20.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Irish Research Council for Science, Engineering and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- locus coeruleus, noradrenergic system, pupil size, pupillometry, BOLD signal, oddball paradigm, stimulus relevance
- MeSH terms
- Adult, Attention, Brain Mapping, Cerebrovascular Circulation, Female, Humans, Locus Coeruleus, Magnetic Resonance Imaging, Male, Middle Aged, Monitoring, Physiologic, Neuropsychological Tests, Oxygen, Pupil, Rest, Signal Processing, Computer-Assisted, Visual Perception, Young Adult
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