Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience

Wager, Tor D.; Atlas, Lauren Y.; Leotti, Lauren A.; Rilling, James K.

doi:10.1523/jneurosci.3420-10.2011

Cited by 276 publications

(272 citation statements)

References 89 publications

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“…This multivariate pattern, henceforth referred to as a brain phenotype for ∆SBP, was derived from the largest neuroimaging study of individual differences in cardiovascular stress reactivity to date, which integrated the use of a standardized stressor battery, cross‐validation testing, and machine learning methods 35, 36, 43. The brain phenotype for ∆SBP accounted for around 9% of the variance in individual differences in stressor‐evoked SBP reactivity (our primary dependent variable), with overall accuracies in predicting normative SBP changes ranging from 0.6 to 0.8 (Figure 3C).…”

Section: Discussionmentioning

confidence: 99%

A Brain Phenotype for Stressor‐Evoked Blood Pressure Reactivity

Gianaros

Sheu

Uyar

et al. 2017

JAHA

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BackgroundIndividuals who exhibit large‐magnitude blood pressure (BP) reactions to acute psychological stressors are at risk for hypertension and premature death by cardiovascular disease. This study tested whether a multivariate pattern of stressor‐evoked brain activity could reliably predict individual differences in BP reactivity, providing novel evidence for a candidate neurophysiological source of stress‐related cardiovascular risk.Methods and ResultsCommunity‐dwelling adults (N=310; 30–51 years; 153 women) underwent functional magnetic resonance imaging with concurrent BP monitoring while completing a standardized battery of stressor tasks. Across individuals, the battery evoked an increase systolic and diastolic BP relative to a nonstressor baseline period (M ∆systolic BP/∆diastolic BP=4.3/1.9 mm Hg [95% confidence interval=3.7–5.0/1.4–2.3 mm Hg]). Using cross‐validation and machine learning approaches, including dimensionality reduction and linear shrinkage models, a multivariate pattern of stressor‐evoked functional magnetic resonance imaging activity was identified in a training subsample (N=206). This multivariate pattern reliably predicted both systolic BP (r=0.32; P<0.005) and diastolic BP (r=0.25; P<0.01) reactivity in an independent subsample used for testing and replication (N=104). Brain areas encompassed by the pattern that were strongly predictive included those implicated in psychological stressor processing and cardiovascular responding through autonomic pathways, including the medial prefrontal cortex, anterior cingulate cortex, and insula.ConclusionsA novel multivariate pattern of stressor‐evoked brain activity may comprise a phenotype that partly accounts for individual differences in BP reactivity, a stress‐related cardiovascular risk factor.

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Section: Discussionmentioning

confidence: 99%

A Brain Phenotype for Stressor‐Evoked Blood Pressure Reactivity

Gianaros

Sheu

Uyar

et al. 2017

JAHA

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“…As contrasted with a more cognitivelymediated PA in adults, one might speculate that in children, reward-related motivational, emotional appraisal (e.g. safety) and associated changes in intra-subcortical limbic-related circuitries (61), as well as attachment are critical for the mediation of PA.…”

Section: Placebo Analgesia Responsesmentioning

confidence: 98%

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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“…For each participant, we conducted a general linear model (GLM) in SPM8 including regressors for conditions of interest (ie, the 'buy' decision epoch-the period in which decisions to purchase or decline cannabis were made-for purchased and declined offers convolved with the canonical hemodynamic response function) and conditions of no interest (motion regressions), with a high-pass filter of 128 s. This allowed us to summarize brain activation in each voxel for purchased vs declined offers. A machine learning regression approach, Least Absolute Shrinkage and Selection Operator-Regularized Principal Components Regression (LASSO-PCR; Wager et al, 2011), was applied in MATLAB (MathWorks, Natick, MA) to generate the whole-brain pattern of regression weights (the neural signature) that best differentiated between purchased and declined fMRI activation maps. We employed a leave-one-out cross validation approach, with data from 16 participants used as training data to generate the neural signature that was then applied prospectively to differentiate brain activity associated with purchased from declined cannabis offers in the left-out participant; data from each participant were sequentially excluded from the derivation of the signature to serve as the predicted data set.…”

Section: Experimental Protocolmentioning

confidence: 99%

An fMRI-Based Neural Signature of Decisions to Smoke Cannabis

Bedi

Lindquist

Haney

2015

Neuropsychopharmacol

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Drug dependence may be at its core a pathology of choice, defined by continued decisions to use drugs irrespective of negative consequences. Despite evidence of dysregulated decision making in addiction, little is known about the neural processes underlying the most clinically relevant decisions drug users make: decisions to use drugs. Here, we combined functional magnetic resonance imaging (fMRI), machine learning, and human laboratory drug administration to investigate neural activation underlying decisions to smoke cannabis. Nontreatment-seeking daily cannabis smokers completed an fMRI choice task, making repeated decisions to purchase or decline 1-12 placebo or active cannabis 'puffs' ($0.25-$5/puff). One randomly selected decision was implemented. If the selected choice had been bought, the cost was deducted from study earnings and the purchased cannabis smoked in the laboratory; alternatively, the participant remained in the laboratory without cannabis. Machine learning with leave-one-subject-out cross-validation identified distributed neural activation patterns discriminating decisions to buy cannabis from declined offers. A total of 21 participants were included in behavioral analyses; 17 purchased cannabis and were thus included in fMRI analyses. Purchasing varied lawfully with dose and cost. The classifier discriminated with 100% accuracy between fMRI activation patterns for purchased vs declined cannabis at the level of the individual. Dorsal striatum, insula, posterior parietal regions, anterior and posterior cingulate, and dorsolateral prefrontal cortex all contributed reliably to this neural signature of decisions to smoke cannabis. These findings provide the basis for a brain-based characterization of drug-related decision making in drug abuse, including effects of psychological and pharmacological interventions on these processes.

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Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience

Cited by 276 publications

References 89 publications

A Brain Phenotype for Stressor‐Evoked Blood Pressure Reactivity

A Brain Phenotype for Stressor‐Evoked Blood Pressure Reactivity

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

An fMRI-Based Neural Signature of Decisions to Smoke Cannabis

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