Individual differences in reward responding explain placebo-induced expectations and effects
Open accessAbstract
Expectations, positive or negative, are modulating factors influencing behavior. They are also thought to underlie placebo effects, impacting perceptions and biological processes. Using healthy human subjects, we examined the role of the nucleus accumbens (NAC), a region centrally involved in the encoding of reward expectation, in the formation of placebo responses. Employing functional molecular imaging, activation of NAC dopamine (DA) release was observed during placebo administration and related to its anticipated effects, perception-anticipation mismatches, and placebo effect development. In additional functional MRI studies, the expectation of monetary gain increased NAC synaptic activity in a manner proportional to placebo-induced DA release, anticipated effects, perception-anticipation differentials, and actual placebo effects. Individual variations in NAC response to reward expectation accounted for 28% of the variance in the formation of placebo analgesia.
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The experience of pain results from both sensory input and psychological variables such as personality traits and anxiety level.
“The experience of pain results from both sensory input and psychological variables such as personality traits and anxiety level1–5.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [3]
The experience of pain is strongly affected by other psychological variables such as optimism, anxiety, suggestibility, and reward responsiveness.
“Our interest in individual differences was motivated by our own and others’ findings that the experience of pain is strongly affected by other psychological variables such as optimism, anxiety, suggestibility, and reward responsiveness1–5.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [3]
Individual variation in ventral striatal response to reward expectation accounted for 28% of the variance in the magnitude of placebo analgesia.
“It has been shown that individual variation in ventral striatal response to reward expectation accounted for 28% of the variance in the magnitude of placebo analgesia (Scott et al., 2007).”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Scott et al., 2007
The dopaminergic system mediated expectation formation in placebo manipulation.
“Previous studies have provided evidence that the dopaminergic system mediated expectation formation in placebo manipulation (50)”
From Placebo treatment facilitates social trust and approach behavior (2018) · cites this paper as [50]
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- Authors
- Scott, D. J., Stohler, C. S., Egnatuk, C. M., Wang, H., Koeppe, R. A., & Zubieta, J.-K.
- Affiliations
- University of Michigan (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Zubieta, Jon-Kar
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 55
- Issue
- 2
- Pages
- 325-336
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2079957063
- Cited by
- 466
- References
- 63
- Citations by year
- 2026: 7 · 2025: 24 · 2024: 12 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 27 · 2019: 24 · 2018: 27 · 2017: 19 · 2016: 24 · 2015: 28 · 2014: 48 · 2013: 38 · 2012: 27
- FWCI
- 14.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2239 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (R01DA016423)
- National Institute of Dental and Craniofacial Research (R01DE015396, R01 DE 15396)
- National Center for Complementary and Integrative Health (R01AT001415)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- placebo effect, reward anticipation, nucleus accumbens, dopamine release, individual differences, placebo analgesia, expectations formation, monetary gain, synaptic activity
- MeSH terms
- Adult, Dopamine, Female, Games, Experimental, Humans, Individuality, Magnetic Resonance Imaging, Male, Nucleus Accumbens, Pain, Reference Values, Reward, Set, Psychology, Placebo Effect, Positron-Emission Tomography
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