CoChat
Sign Up
Cited by 1,387Neurotransmitter Receptor Influence on BehaviorNeural dynamics and brain functionNeuroscience and Neuropharmacology Research

Relationships between Pupil Diameter and Neuronal Activity in the Locus Coeruleus, Colliculi, and Cingulate Cortex

Open access
Joshi, Siddhartha, Li, Yin, Kalwani, Rishi M., Gold, Joshua I.·2016·Neuron
DOI 10.1016/j.neuron.2015.11.028PMC PMC4707070
Open this paper in CoChat — free accountOpen PDF

Abstract

Changes in pupil diameter that reflect effort and other cognitive factors are often interpreted in terms of the activity of norepinephrine-containing neurons in the brainstem nucleus locus coeruleus (LC), but there is little direct evidence for such a relationship. Here, we show that LC activation reliably anticipates changes in pupil diameter that either fluctuate naturally or are driven by external events during near fixation, as in many psychophysical tasks. This relationship occurs on as fine a temporal and spatial scale as single spikes from single units. However, this relationship is not specific to the LC. Similar relationships, albeit with delayed timing and different reliabilities across sites, are evident in the inferior and superior colliculus and anterior and posterior cingulate cortex. Because these regions are interconnected with the LC, the results suggest that non-luminance-mediated changes in pupil diameter might reflect LC-mediated coordination of neuronal activity throughout some parts of the brain.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neuron.2015.11.028

Cites

96 of 96 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Surprise as measured by pupil dilations is closely coupled with the release of norepinephrine in the brainstem's locus coeruleus.

    “Surprise as measured by pupil dilations is closely coupled with the release of norepinephrine in the brainstem’s locus coeruleus (Joshi et al., 2016).”

    From Predicting as a learning strategy (2021) · cites this paper as Joshi et al., 2016

    The Results section on startling events reports that unexpected tones dilated monkeys’ pupils and that the pupil response had a weak but reliable trial-by-trial relationship with LC-region neural activity. The Discussion links pupil fluctuations to LC-region activity and proposes associated norepinephrine release throughout the brain. The study did not measure norepinephrine release or establish that pupil dilation measures surprise specifically, so the claim states the coupling more strongly than the evidence supports. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ACC and AI project to or are adjacent to VTA and SN, with multisynaptic routes via habenula.

    “which project to or are adjacent to VTA and SN3,22,29–33,54,55 (with multisynaptic routes via habenula56,57)”

    From Interpretable abstractions of artificial neural networks predict behavior and neural activity during human information gathering (2026) · cites this paper as [31]

  • The locus coeruleus may modulate fluctuations in global network topology through phasic alterations in neural gain.

    “The locus coeruleus (Aston-Jones and Cohen, 2005) is known to modulate pupil diameter (Joshi et al., 2016), and thus by inference, may play a role in the modulation of fluctuations in global network topology through phasic alterations in neural gain (Eldar et al., 2013).”

    From The Dynamics of Functional Brain Networks: Integrated Network States during Cognitive Task Performance (2016) · cites this paper as Joshi et al., 2016

  • The magnitude and variability in these correlation coefficients were comparable to previous reports linking locus coeruleus cell spiking to pupil size in primates.

    “The magnitude and variability in these correlation coefficients were comparable to previous reports linking locus coeruleus cell spiking to pupil size (a measure of arousal) in primates (Joshi et al., 2016).”

    From Ancestral Circuits for the Coordinated Modulation of Brain State (2017) · cites this paper as Joshi et al., 2016

  • Noradrenergic locus coeruleus neurons were significantly correlated with alertness states, displaying greater activity prior to fast RT trials.

    “we found that noradrenergic locus coeruleus neurons were significantly correlated with alertness states, displaying greater activity prior to fast RT trials (Figures 3B and 3C).”

    From Ancestral Circuits for the Coordinated Modulation of Brain State (2017) · cites this paper as Joshi et al., 2016

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Schmidt HS Fortin LD Fortin LD Schmidt HS Guilleminault Electronic pupillography in disorders of arousal Sleeping and waking disorders: Indication and technique 1982 127 143 Addison-Wesley Menlo Park, CA

Cited by

Sorted by citations

Related

Authors
Joshi, S., Li, Y., Kalwani, R. M., & Gold, J. I.
Affiliations
  • University of Pennsylvania (US)
  • Temple University (US)
Corresponding author
Joshi, Siddhartha
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2016-01
Volume
89
Issue
1
Pages
221-234
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2015.11.028
PMC
PMC4707070
OpenAlex
W2210396547
Cited by
1,387
References
96
Citations by year
2026: 148 · 2025: 155 · 2024: 157 · 2023: 143 · 2022: 146 · 2021: 176 · 2020: 113 · 2019: 117 · 2018: 98 · 2017: 80 · 2016: 54
FWCI
35.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01MH098899, R21MH093904)
  • National Eye Institute (P30EY001583)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
pupil size, locus coeruleus, norepinephrine, inferior colliculus, superior colliculus, cingulate cortex, neuronal activity, effort, single-unit activity, brainstem arousal
MeSH terms
Animals, Cerebellar Cortex, Electric Stimulation, Locus Coeruleus, Macaca mulatta, Male, Neurons, Norepinephrine, Pupil

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review