How Pain Prediction Affects Perception

Post by Elisa Guma

What's the science?

Our past experiences often shape our expectations of the future, which in turn can influence how we perceive future events. Previous work has shown that our expectation of how painful a stimulus will be can influence our perception of that stimulus and our response to it. Moreover, expectations about pain (e.g., following placebo treatments) can be surprisingly resistant to change, acting much like self-fulfilling prophecies. The brain and behavioural mechanisms underlying these phenomena are largely unknown. This week in Nature: Human Behavior Jepma and colleagues used behavioural assessments and functional magnetic resonance imaging (fMRI) to investigate how expectations about pain affect pain experience, and why expectations of high or low pain sometimes persist despite evidence to the contrary.

How did they do it?

The authors designed two experiments in which they independently manipulated predictive pain cues (to investigate pain expectation), and the intensity of a pain stimulus (to investigate pain perception). In both studies, participants first went through a learning phase where they learned to associate abstract visual cues with either low or high temperatures (displayed on thermometers). In the subsequent test phase participants were presented with both sets of cues followed by a painful heat stimulus to the inner forearm in the first study, and to the lower leg in the second study. Unbeknownst to the participants, the cues were no longer predictive of heat intensity. Participants were instructed to rate how much pain they expected following each cue, and how much pain they experienced following each heat stimulus. In the second study, fMRI activity was also recorded. The authors tested responses in a measure called the Neurologic Pain Signature (NPS); a measure of activity across brain areas validated to be sensitive and specific to pain in tests performed to date. They used these brain areas to guide their investigation of brain signatures of pain perception and expectation in this study. Finally, the authors used computational models to quantify their findings, using both a reinforcement learning model  and a Bayesian model.

What did they find?

The authors found evidence that cue based expectations influence pain perception; higher pain expectation led to larger subjective pain rating, and to higher brain activity in the neurologic pain network. In addition, larger pain rating and higher activity in the NPS predicted higher pain expectation in subsequent trials with the same cue. The authors also observed a confirmation bias in learning about pain intensity, with stronger learning from new pain stimuli that confirmed one's initial pain expectation than from new pain stimuli that disconfirmed expectations. The computational models allowed the authors to determine that participants' pain expectations influenced both perceived pain and participants' learning rates. Finally, participants with stronger confirmation biases in their learning rate also showed a greater confirmation bias in the updating of pain-anticipatory brain activity in regions important for threat, anxiety, and value-based decision-making.

What's the impact?

This study is among the first to identify brain and behavioural processes underlying self-reinforcing expectations. This may have implications for chronic pain, as self-reinforcing expectations may be part of what makes people transition from acute to chronic pain. The findings may help in our understanding of how perceptual learning is applied to pain, and can be applied to individuals at risk for chronic pain. More broadly, it may help us understand how beliefs are sometimes so resistant to new evidence.

Jepma et al. Behavioural and neural evidence for self-reinforcing expectancy effects on pain. Nature: Human Behavior (2018). Access the original scientific publication here.

Sensory Cues Can Promote Riskier Choices

Post by Stephanie Williams

What's the science?

We know from animal studies that reward-related cues like noises (chimes) or visual signals (flashing lights) can influence animals to make risky decisions. It is still unknown if reward-related cues can influence humans in a similar way. It is also unclear how the cues would exert their effects on decision making. This week in the Journal of Neuroscience, Cherkasova and colleagues assessed the effects of reward-associated sensory cues on the promotion of risky decisions in humans.

How did they do it?

The authors randomized 131 human subjects to play two computerized games, either with or without visual (i.e. stacks of bills or coins) and auditory (casino chiming noises) cues, to test whether these cues affected decision making. The first game, the Iowa Gambling Task (IGT), consisted of four decks of cards, and the participant’s goal was to win as much money as possible by selecting cards from the decks. Some decks were more advantageous than others, and each time the participant selected a card, they either won or lost money. To win the maximum amount of money, participants should have chosen cards from the two of the four decks that had low risk/low reward cards (no big wins, but no big losses either). In the second game, the Vancouver Gambling Task (VGT), participants had to choose between a low chance of winning a larger amount of money, and a higher chance of winning a smaller amount of money. Participants were repeatedly presented with various pairs of potential winnings. The researchers used the participant’s choices in this task to create a model of a participants' willingness to take risks.

The authors tracked several physiological measurements including eye movements and pupil dilation, which is related to arousal. Eye tracking data was analyzed to measure time spent looking at probability information (participants were shown pie charts representing probabilities of winning during the VGT task). Pupil size was analyzed from the VGT to see whether the auditory and visual effects were related to pupil dilation, and whether dilation was related with riskier choices.     

What did they find?

To understand the effect of the sensory cues on decision making, the authors applied various models that took into account different variables related to their data. They found that the presence of sensory cues did not cause subjects to make a greater number of disadvantageous choices in the IGT task. In contrast, during the VGT task, they found that subjects made riskier choices and spent less time paying attention to probability information when playing the cued task than when playing the uncued VGT task. The authors were able to relate the risk enhancement to subject’s decreased consideration of reward probability when making choices, rather than changes in the subject’s perceived expected value. It is still unclear what mechanism swayed participant's attention away from the probability information.

Several findings emerged from the authors analysis of pupil dilation during the VGT. In both the cued and uncued tasks, subjects showed increased pupil dilation during risky decisions. This was a significant finding, as it provides novel confirmation of a strong association between pupil dilation and risky choice. In the cued task, the authors found that pupil dilation associated with decision-making and anticipation was increased. This finding highlights the effect of the sensory cue in increasing arousal. The authors also found that the risk-promoting and arousal-promoting effects of cues were separate and independent effects.

What's the impact?

This is the first paper to confirm that sensory reward cues promote riskier decisions in humans. Previous studies had shown that reward sensory cues could increase arousal, and change the way people estimate profits, but no one had yet shown that they could directly affect choice. Their findings suggest that the sensory cues in particular environments (ie. Casinos) could affect decision making, which could be used to help explain why individuals suffering from addiction may make risky decisions.

Cherkasova, M. et al., Win-concurrent sensory cues can promote riskier choice. The Journal of Neuroscience (2018). Access the original scientific paper here.

Prenatal Exposure to Neurotransmitter-Targeting Medications and Autism

Post by Sarah Hill

What's the science?

Is the use of psychiatric or neurologic medications during pregnancy associated with higher (or lower) incidence of autism spectrum disorders (ASD) in children? This has been a difficult question to answer as pregnant women are often excluded from clinical trials. Further, separating out whether effects on children stem from exposure to medications or from increased risks associated with the mother's medical diagnosis has not been possible using prior study design methods. This week in JAMA Psychiatry, Janecka and colleagues use an innovative study design strategy to test whether prenatal exposure to drugs that act on neurotransmitter systems is associated with increased or decreased prevalence of ASD.  

How did they do it?

The authors obtained data for 95,978 children born between 1997 and 2007 from a health maintenance organization in Meuhedet, Israel, and verified that maternal prescription rates and ASD prevalence in the sample matched the national rates. The sample population consisted of all children who had received an ASD diagnosis before 2015, randomly sampled ASD and non-ASD individuals, and all siblings of ASD and non-ASD individuals. They then grouped individuals based on the neurotransmitter system that was targeted by the mother's medication (55 non-mutually exclusive medication groups in total; for example, the serotonin system), in contrast to previous studies which grouped individuals by medication. They next calculated the hazard ratios, a measure of the relative risk of outcome in one group compared to another group, using a statistical method that simultaneously evaluates how several factors influence the rate of a particular event happening (in this case, an ASD diagnosis) at a particular timepoint [Cox proportional hazards regression]. Importantly, the models tested also took into account the mothers' psychiatric or neurological conditions (e.g. anxiety disorder), number of maternal medical diagnoses within 1 year prior to birth (e.g. acute bronchitis), birth year, maternal and paternal age, and socioeconomic status.     

What did they find?

Due to the number of factors that may play a role, establishing a clear relationship between prenatal exposure to psychiatric drugs and altered risk of ASD is difficult. A link between neuronal acetylcholine receptor α antagonists, such as certain medications used to treat epilepsy, and increased rates of ASD was the only clear finding in this study that remained significant after accounting for all other factors, although there were very few women who took these medications during pregnancy. Certain medications used as anti-analgesic/anti-inflammatory agents were found to be associated with decreased rates of ASD when the number of maternal diagnoses was also taken into account, though the associations were not statistically significant in subsequent analyses. The authors found no other statistically significant links between medication group and ASD when all variables were considered, indicating that the use of most neurologic medications, including antidepressants and antipsychotics, during pregnancy is not associated with increased or decreased prevalence of ASD. Of all factors considered, the number of maternal medical diagnoses appeared to have the greatest effect on whether a relationship between medication group and ASD was found, suggesting it may be confounding previously observed associations.

What's the impact?

In contrast to previous reports, this study found no evidence that the use of drugs that act on the serotonin system (as well as most other neurotransmitter systems) during pregnancy increase a child's risk of ASD. Instead, it suggests that maternal general health can impact the risk of ASD, indicating that prior studies that found a link between prenatal medication use and ASD may need to be re-evaluated. Large-scale population-based studies such as this one are imperative for informing prescription practices of doctors treating pregnant patients.  

Janecka et al. Association of Autism Spectrum Disorder with prenatal exposure to medication affecting neurotransmitter systems. JAMA Psychiatry (2018). Access the original scientific publication here.