Individual Differences in Reward Responding Explain Placebo-Induced Expectations and Effects

Scott, David J.; Stohler, Christian S.; Egnatuk, Christine M.; Wang, Heng; Koeppe, Robert A.; Zubieta, Jon Kar

doi:10.1016/j.neuron.2007.06.028

Cited by 410 publications

(321 citation statements)

References 61 publications

(76 reference statements)

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“…Each hotspot may be merely a cubic millimeter or so in volume in the rodent brain (and should be a cubic centimeter or so in humans, if proportional to whole brain volume) and is capable of generating enhancements of 'liking' reactions to a sensory pleasure such as sweetness, when opioid, endocannabinoid, or other neurochemical receptors within it are stimulated (Mahler et al 2007;Peciña and Berridge 2005;Peciña et al 2006;Smith and Berridge 2005;Smith et al 2008). Anatomical hotspot coding indicates a surprisingly high degree of localization of function for sufficient-cause pleasure mechanisms in the brain, and hotspot segregation within a limbic structure might provide a way for opioid or related brain signals to disambiguate pleasure versus pain via localization of function if the same neurochemical signal mediates both types of valence (Petrovic 2008;Reynolds and Berridge 2002;Scott et al 2007;Smith et al 2008;Wager et al 2004;Wightman et al 2007).…”

Section: Pleasure Generators: Hedonic Hotspots In the Brainmentioning

confidence: 99%

Affective neuroscience of pleasure: reward in humans and animals

2008

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Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness.

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Section: Pleasure Generators: Hedonic Hotspots In the Brainmentioning

confidence: 99%

Affective neuroscience of pleasure: reward in humans and animals

2008

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“…A well-known feature of placebo treatment is individual variability in the magnitude of the placebo response. These behavioral differences are known to reflect differences in central placebo processing (15,23). We identified covariance with the behavioral placebo response within emotion appraisal circuitry by adding a regressor with each subject's average placebo improvement (placebo > control) for each stimulus type to the fMRI group analysis setup (placebo > control) for each stimulus.…”

Section: Placebo Responses Correlated With Bold Signal Increases In Ementioning

confidence: 99%

“…Activity in these regions predicts individual placebo analgesia more accurately than regions involved in cognitive control or pain processing (21). This network is dependent on endogenous opioids (16,19,22) and interacts with the mesolimbic dopamine system (23)(24)(25) to reduce pain by inhibiting nociceptive signaling (15). Because these regions collectively are involved in valuation and reward-related processing more generally (26,27), and for reasons of clarity and brevity, we will refer to this set of regions as "emotion appraisal circuitry.…”

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confidence: 99%

Placebo improves pleasure and pain through opposite modulation of sensory processing

Ellingsen

Wessberg

Eikemo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Placebo analgesia is often conceptualized as a reward mechanism. However, by targeting only negative experiences, such as pain, placebo research may tell only half the story. We compared placebo improvement of painful touch (analgesia) with placebo improvement of pleasant touch (hyperhedonia) using functional MRI and a crossover design. Somatosensory processing was decreased during placebo analgesia and increased during placebo hyperhedonia. Both placebo responses were associated with similar patterns of activation increase in circuitry involved in emotion appraisal, including the pregenual anterior cingulate, medial orbitofrontal cortex, amygdala, accumbens, and midbrain structures. Importantly, placebo-induced coupling between the ventromedial prefrontal cortex and periaqueductal gray correlated with somatosensory decreases to painful touch and somatosensory increases to pleasant touch. These findings suggest that placebo analgesia and hyperhedonia are mediated by activation of shared emotion appraisal neurocircuitry, which down-or upregulates early sensory processing, depending on whether the expectation is reduced pain or increased pleasure.expectancy | neuroimaging | hedonic feelings M edical treatments aim to provide relief from pain and aversive states. Consequently, research on placebo effects has focused on relief of negative hedonic feelings, like pain and displeasure (1). In contrast, placebo improvement of positive hedonics has received little attention. However, pain and pleasure processes are tightly linked. Relief from pain can induce a pleasant experience underpinned by activation of reward neurocircuitry (2-4). Moreover, a painful stimulus can even be perceived as pleasant when it represents relief from a more severe outcome (5). In line with this pain-pleasure link, placebo analgesia can be conceptualized as a type of reward mechanism; pain relief is a better outcome than the alternative (6-8) and is typically framed as a gain (improvement of pain) (9).Like pain, pleasure is greatly affected by context and expectation (10). Manipulation of people's beliefs about the price of a wine (11), the amount of fruit in a sweet drink (12), the richness of a skin cream (13), and who is caressing them (14) alters the experienced pleasantness of these stimuli.Placebo-induced improvement of aversive experiences (e.g., pain, anxiety, unpleasant taste) is often underpinned by a decrease in central sensory processing. Placebo analgesia is characterized by decreases in the thalamus, posterior insula (pINS), and primary and secondary somatosensory areas (SI and SII) (15)(16)(17). Placebo reduction of affective responses to unpleasant visual stimuli is similarly underpinned by suppression of visual processing (8). It is not, however, known whether placeboenhanced pleasantness (i.e., hyperhedonia) also alters early stages of sensory processing, or if this change is encoded in higher-level valuation areas.Functional neuroimaging studies have revealed that the ventromedial prefrontal cortex (vmPFC), amygdala, ventral...

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“…Dopaminergic activity has also been associated with personality traits such as reward susceptibility (18), which partially predicts the magnitude of PA (18,19). More recently, the personality dimension of magical thinking (MT), which is thought to be related to dopaminergic function (20), has been implicated in modulating expectation-related lateralized PA in healthy adults (21).…”

Section: Introductionmentioning

confidence: 99%

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Kempler

Kossowsky

Schwarz

et al. 2014

The Journal of Pain

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Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat-pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned -stratified for MT and gender -to either an analgesia-expectation or a controlexpectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearmside: low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. PERSPECTIVE: The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children from 6 to 9 years of age. Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. Conflicts of Interest and Source of FundingThe authors declare that there is no conflict of interest. This research was supported by the University of Basel.Running Title: Placebo Analgesia and Magical Thinking in Children Krummenacher et al., 2014 1 Abstract Objective: Higher brain functions such as expectations and beliefs shape the experience of pain. This is most evident in context-induced placebo analgesia (PA), which was recently shown in adults to interact with the trait of magical thinking (MT).In children, PA and the possible relationship between PA and MT has remained unexplored.Methods: Using a lateralized heat-pain paradigm, we investigated the possible modulatory role of PA expectation and MT in response to nociceptive stimuli on the right and left forearm.Participants were 49 right-handed children (6-9 years). In a between-subjects design, half of them were either randomly -stratified for MT and gender -assigned to an analgesia-expectation or a control-expectation condition. Results:Results indicate that, independent of MT, the placebo procedure significantly increased both heat pain threshold (...

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Individual Differences in Reward Responding Explain Placebo-Induced Expectations and Effects

Cited by 410 publications

References 61 publications

Affective neuroscience of pleasure: reward in humans and animals

Affective neuroscience of pleasure: reward in humans and animals

Placebo improves pleasure and pain through opposite modulation of sensory processing

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

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