Noradrenergic and Cholinergic Modulation of Belief Updating
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To make optimal predictions in a dynamic environment, the impact of new observations on existing beliefs—that is, the learning rate—should be guided by ongoing estimates of change and uncertainty. Theoretical work has proposed specific computational roles for various neuromodulatory systems in the control of learning rate, but empirical evidence is still sparse. The aim of the current research was to examine the role of the noradrenergic and cholinergic systems in learning rate regulation. First, we replicated our recent findings that the centroparietal P3 component of the EEG—an index of phasic catecholamine release in the cortex—predicts trial-to-trial variability in learning rate and mediates the effects of surprise and belief uncertainty on learning rate (Study 1, n = 17). Second, we found that pharmacological suppression of either norepinephrine or acetylcholine activity produced baseline-dependent effects on learning rate following nonobvious changes in an outcome-generating process (Study 1). Third, we identified two genes, coding for α2A receptor sensitivity ( ADRA2A) and norepinephrine reuptake ( NET), as promising targets for future research on the genetic basis of individual differences in learning rate (Study 2, n = 137). Our findings suggest a role for the noradrenergic and cholinergic systems in belief updating and underline the importance of studying interactions between different neuromodulatory systems.
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Baseline task performance in a placebo condition frequently predicts the behavioral effects of catecholaminergic manipulations.
“Second, baseline task performance (in a placebo condition) was considered, as it frequently predicts the behavioral effects of catecholaminergic manipulations (Cools & Robbins, 2004; Jepma et al., 2016, 2018) and therefore may indicate an individual’s baseline placement on the inverted-U curve relating dopamine activity and WM performance.”
From Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating (2020) · cites this paper as Jepma et al., 2018
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- Figure A1. (This figure is related to Figure 6 in the main text.) Baseline-dependent drug effects on learning rate for different levels of change point probability. Trials were divided in nine bins, using the change point probabilities indicated on the left side of each plot as cutoff values. Note that, as change point probability was not equally distributed, the different bins contained different numbers of trials. The gray distributions are permutation distributions of the correlation coefficients predicted by regression to the mean in each bin, and the red lines indicate the observed correlations. 1818 Journal of Cognitive Neuroscience Volume 30, Number 12
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Wurm, F., Walentowska, W., Ernst, B., Severo, M. C., Pourtois, G., & Steinhauser, M. (2021) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_01777 · Cited by 10 · see citing works
Catecholamines reduce choice history biases in perceptual decision making
de Gee, J. W., Kloosterman, N. A., Braun, A., & Donner, T. H. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003361 · Cited by 6 · see citing works
Systematic review: Effects of cholinergic signaling on cognition in human pharmacological studies
Dan, Y. R., Christakou, A., & Karin Roelofs, A. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106408 · Cited by 5 · see citing works
MacCormack, J. K., Armstrong‐Carter, E., Humphreys, K. L., & Muscatell, K. A. (2021) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsab047 · Cited by 5 · see citing works
Narasimhan, S., Schriver, B. J., & Wang, Q. (2023) · Journal of Neurophysiology · doi:10.1152/jn.00309.2022 · Cited by 4 · see citing works
A dynamical systems model of arousal-driven behavioural state transitionsPreprint
Johnson, P. A., Nieuwenhuis, S., Mejías, J. F., & Urai, A. E. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.31.685593 · Cited by 4 · see citing works
Self-citationPrediction errors indexed by the P3 track the updating of complex long-term memory schemasPreprint
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Jongkees, B. J. (2019) · doi:10.31234/osf.io/bpv2y · Cited by 3 · see citing works
Brancaccio, A., Tagliaferri, M., Miniussi, C., & Cattaneo, L. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121335 · Cited by 2 · see citing works
Fluctuations in arousal reflect latent state transitions that facilitate behavioural optimization
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An Integrative and Mechanistic Model of Impaired Belief Updating in Schizophrenia
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Electrophysiological correlates of (mis)judging social information
Wischnewski, M., Hörberg, M. O. Y., & Schutter, D. J. L. G. (2024) · Psychophysiology · doi:10.1111/psyp.14590 · Cited by 1 · see citing works
Absence of Systematic Effects of Internalizing Psychopathology on Learning Under UncertaintyPreprint
Satti, M. H., Wille, K., Nassar, M. R., Cichy, R. M., Schuck, N. W., Dayan, P., & Bruckner, R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.12.653409 · Cited by 1 · see citing works
Absence of Systematic Effects of Internalizing Psychopathology on Learning Under UncertaintyPreprint
Satti, M. H., Wille, K., Nassar, M. R., Cichy, R. M., Schuck, N. W., Dayan, P., & Bruckner, R. (2025) · eLife · doi:10.7554/elife.107611.1 · Cited by 1 · see citing works
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Greenhouse‐Tucknott, A., Foucault, C., Buot, A., & Meyniel, F. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.26.708148 · Cited by 1 · see citing works
Absence of Systematic Effects of Internalizing Psychopathology on Learning Under UncertaintyPreprint
Satti, M. H., Wille, K., Nassar, M. R., Cichy, R. M., Schuck, N. W., Dayan, P., & Bruckner, R. (2025) · eLife · doi:10.7554/elife.107611
Implication of the locus coeruleus in effort processing : electrophysiological studies
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Plat, H., Chevallier, C., Piccin, A., Marchand, A. R., Naudé, J., & Coutureau, É. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536535123
Change-point oddball elicits pupil-linked signatures of Bayesian belief updatingPreprint
Kopel, L., Hoomans, J. M., van Gastel, E., Tijhuis, J. V., de Graaf, M., Shafik, M., Matthijsse, S., Murphy, P. R., van Gaal, S., Mototaka Suzuki, A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.25.754382
Self-citation
- Authors
- Jepma, M., Brown, S. B. R. E., Murphy, P. R., Koelewijn, S. C., de Vries, B., van den Maagdenberg, A. M., & Nieuwenhuis, S.
- Affiliations
- Leiden University (NL)
- Leiden University Medical Center (NL)
- Leiden University Medical Centre
- Venue
- Journal of Cognitive Neuroscience
- Publisher
- MIT Press
- Published
- 2018-12
- Volume
- 30
- Issue
- 12
- Pages
- 1803-1820
- ISSN
- 0898-929X (ISSN-L)
- 1530-8898
- OpenAlex
- W2886901971
- Cited by
- 39
- References
- 80
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 6
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cognitive Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Universiteit van Amsterdam
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- belief updating, learning rate, noradrenergic system, cholinergic system, P300, catecholamine release, surprise, belief uncertainty, norepinephrine, acetylcholine, ADRA2A, .NET, individual differences, neuromodulation
- MeSH terms
- Acetylcholine, Adolescent, Adult, Brain, Clonidine, Double-Blind Method, Electroencephalography, Female, Humans, Learning, Male, Norepinephrine, Scopolamine, Receptors, Adrenergic, alpha-2, Cross-Over Studies, Cholinergic Antagonists, Uncertainty, Norepinephrine Plasma Membrane Transport Proteins, Young Adult, Genetic Association Studies, Adrenergic alpha-2 Receptor Agonists, Anticipation, Psychological
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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.
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