International Journal of Psychology, 2014 Vol. 49, No. 6, 488–497, DOI: 10.1002/ijop.12072

Motivation and expectancy influences in placebo responding: The mediating role of attention Carrie Aigner and Soren Svanum Indiana University Purdue University Indianapolis, Indianapolis, IN, USA

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rawing upon research in perception and motivation, the current study proposes a motivation-attention model of placebo in which more motivated persons pay greater attention to placebo-related stimuli, directly influencing placebo response. We manipulated both motivation to respond to placebo and expectations of placebo response in a 2 × 2 design. Participants (N = 152) evaluated a series of placebo pheromones (slightly scented water) of potential romantic dates and made desirability ratings. Consistent with hypotheses, more highly motivated participants demonstrated greater placebo responses, as evidenced by higher desirability ratings of the “pheromone” and greater variability among ratings, when compared to less motivated participants. Moreover, the relation between motivation and placebo response was mediated by attention. Contrary to expectations, we found no effect for expectancy. These findings highlight the importance of motivation and the mediating factor of attention in placebo and support goal-oriented models of placebo. Keywords: Placebo; Expectancy; Motivation.

Placebo is broadly conceptualised as an inert substance or treatment that produces beneficial change. Placebo is loosely related to the therapeutic effects associated with constructs such as hope (Richman et al., 2005), optimism (Scheier & Carver, 1992) and more controversially, religiosity (Goldman, 1985). Placebo has been found to be an important component of treatments including psychological and pharmacological treatment of depression (Kirsch & Sapirstein, 1998), transplant surgery for Parkinson’s (McRae, Cherin, Yamazaki, & Diem, 2004) and analgesia (Vase, Price, Verne, & Robinson, 2004), to name a few. Although some view placebo factors as a nuisance, superfluous to active treatment, others have presented placebo as an important component of treatment with untapped potential for enhancing treatment effects (Kaptchuk et al., 2008). Capitalising on placebo’s full potential begins with an understanding of the process involved in producing placebo change. Attempts to explain how placebo effects are produced in therapeutic settings have typically drawn upon expectancy models, which essentially assert that expectations regarding the outcome of a treatment are responsible for producing placebo effects. Simply, if a person believes that a treatment will be effective, they will respond. This placebo expectation is an outcome expectation that a specific emotional or physiological response will result from engaging

in a certain behaviour (e.g. taking a pill). For example, a generally held expectation is that consuming caffeine will lead to feelings of alertness. In experimental research, the deceptive administration of decaffeinated coffee (in which participants are led to believe the coffee contains caffeine) has been found to produce greater increases in heart rate and feelings of alertness than decaffeinated coffee administrated under double-blind conditions (Kirsch & Weixel, 1988). Placebo expectations can be triggered by characteristics of the placebo, experimenter or participant, and are thus, susceptible to subtle variations in study design (Price, Finniss, & Benedetti, 2008). This may help to explain, at least in part, the wide variation in placebo effect sizes across studies (Vase, Riley, & Price, 2002). Although expectancies appear to influence placebo responding, expectancy models may offer an incomplete conceptualisation of placebo. Research suggests that it is not only the expectation of response, but also the motivation for response that is important in producing placebo outcomes (Vase et al., 2004). Broadly, motivation describes the driving force behind goal-directed behaviours (Hyland, 2011). Motivational forces including demand characteristics, self-enhancing motives and the desire for a treatment to produce beneficial effects (e.g. provide pain reduction, produce feelings of alertness) have all been examined within the context of placebo

Correspondence should be addressed to Carrie Aigner, Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, 1155 Pressler St. Unit 1330, Houston, TX 77030, USA. (E-mail: [email protected]).

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models (Geers, Weiland, Kosbab, Landry, & Helfer, 2005; Vase et al., 2004). It has been argued that models that also include these motivational influences provide a more complete understanding of placebo (Geers et al., 2005). For example, a more motivationally driven model, the goal-activation model of the placebo effect, asserts that placebo responding is enhanced when placebo expectations are compatible with motivation for experiencing a particular placebo response (Geers et al., 2005). Indeed, placebo effects have been found to be largest when both expectancy and motivation are maximised (Geers et al., 2005; Vase et al., 2002). All goals are not created as equal. When a placebo is linked to an outcome that is valued and has relevance to a person outside the lab setting, motivation to respond to the placebo is enhanced (Hyland, 2011). For example, the motivation to reduce experimentally manipulated short-lived pain among college students in a lab setting is something quite different from motivation to achieve long-term pain relief among chronic pain patients. A placebo analgesic that promised to deliver pain relief would be valued differently by these two groups. Recent models of placebo have sought to incorporate this more nuanced view of motivation. The motivational concordance theory of placebo proposes that people will respond most highly to a placebo when the placebo is linked to a goal that a person highly desires (Hyland, 2011). Despite theory supporting the importance of motivational forces in placebo, little research has empirically examined the role of motivation in producing placebo effects. Moreover, only a handful of studies have examined the concurrent effects of expectancy and motivation, potential interactions between the two or the relation of each to proposed placebo mediators (Geers et al., 2005). This is especially problematic in research on placebo mechanisms, where causal paths are often inferred without accounting for the influence of other important predictors (Geers, Helfer, Weiland, & Kosbab, 2006). One variable that has been examined as a potential mediator in placebo responding is attention or somatic focus. Some expectancy models propose that expectations of treatment benefit may alter attentional processes (Geers et al., 2006; Lundh, 1987; Vase et al., 2004). When attention is diverted to signs and signals of placebo benefit, placebo responding is produced. Support for the role of attention in placebo can be found in research observing enhanced placebo effects in conditions where participants are told to focus on or document their moment-by-moment responses to a treatment (Geers et al., 2006). Attentional processes have largely been examined within expectancy models of placebo, despite strong evidence in perception literature for a pathway linking motivation to attention (Balcetis & Dunning, 2006; Van Damme, Legrain, Vogt, & Crombez, 2010). In this literature, there is wide range of evidence that everyday © 2014 International Union of Psychological Science

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judgments and experiences are highly responsive to desires, goals and motivations, as apparent in research on motivated reasoning, defensive processing and attentional biases, to name a few. The conceptualisation of attention as a dynamic process subject to the influence of motivational forces provides a useful framework through which to view placebo responses. Motivational factors have been found to influence attention to and the interpretation of stimuli involved in the experience of pain (Van Damme et al., 2010), visual perception (Balcetis & Dunning, 2006) and emotion (Isaacowitz, 2006), among others. This research points to a process in which people motivated to observe a particular stimulus or experience a desired internal state selectively attend to those stimuli and sensations that support their desires and interpret ambiguous stimuli in accordance with these desires, thereby producing the desired belief or state. This is not to discount the role of expectancy, but rather to redefine its role in producing placebo effects. Expectations also influence perception, but possibly through a different pathway. Some theorists in the perceptual bias literature have proposed that expectancies inform people of testable perceptual hypotheses (Pyszczynski & Greenberg, 1987). Thus, motivation may increase attention to and processing of stimuli, but expectancy may help to inform interpretations of these stimuli. Consistently, research on asthma treatment has found that the same placebo (inhaler) can produce different types of placebo responses depending on the verbal expectancies given to participants (Butler & Steptoe, 1986). Taken together, this research provides support for a placebo model in which motivation, causing increased attention to placebo-relevant stimuli, is the main driver of placebo process, and expectancy, informing of possible interpretations, helps to define the nature and type of placebo effect observed. The model is consistent with literature linking motivation to attention and with placebo research demonstrating the importance of both expectancy and motivation in influencing placebo responses. It is an improvement over previous models in its comprehensiveness, clear explanation of mechanisms and theoretical soundness. In this study, we sought to maximise placebo factors, such that mechanisms could more easily be identified and examined. More recent models of placebo propose that placebos linked to goals that are inherently valued will have the strongest effects (Hyland & Whalley, 2007). Researchers have often triggered motivation by linking the placebo to valued goals (e.g. pain relief, stress reduction, sleep enhancement and the desire to be perceived favourably by others; Geers et al., 2005; Hyland & Whalley, 2007). Accordingly, we designed the study such that responding to a placebo “pheromone” in a lab setting was linked to a goal of high value to most single college students: the desire to meet a compatible date. The design was modelled after human pheromone research where

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participants are asked to assess their feelings of attraction and arousal in response to pheromones. Internal cues of attraction can be somewhat ambiguous, as evidenced by research on misattribution of arousal in romantic attraction (White, Fishbein, & Rutstein, 1981). Moreover, research on pheromones in humans suggests that placebo factors may play an important role in pheromone effects of arousal and attraction (Filsinger, Braun, & Woodrow, 1985). Thus, we believe this is an ideal paradigm for examining placebo effects. We designed the study such that students rated feelings of attraction and arousal in response to a placebo pheromone substance. Although this study has design similarities to other placebo research (e.g. rating affective responses to music therapy in Geers et al., 2005), it should be noted that the primary task of rating the desirability qualities of an external placebo stimulus is somewhat unique from the traditional placebo paradigm, in which participants are often asked to rate internal sensations. Nevertheless, the proposed theoretical model can be broadly applied to different methodologies and different types of placebo responses, and the present design represents a good paradigm for examining the theorised pathways in placebo responding. We predicted that the more attention participants pay to the effects of the placebo pheromone, the more opportunity they will have to interpret ambiguous feelings and physiological sensations according to their desires. With this greater attention to the placebo pheromone, we propose participants will be creating an ideal environment to begin to respond to the placebo scents and perceive differences among the identical placebo scents. This is consistent with other research on motivation and attention, which has demonstrated that more highly motivated people tend to look for, and find, differences in ambiguous stimuli (Balcetis & Dunning, 2006).

found some empirical support (e.g. Geers et al., 2005). This assumes that there may be bidirectional influences between expectancy and motivational influences in the placebo effect; high levels of motivation may produce expectancies of placebo benefit, and vice versa. The current study design allowed for an examination of paths and interactions, in order to provide a better understanding of the role of each model variable in producing placebo effects. METHOD Participants Participants were recruited for a study on “dating and attraction” using the psychology department’s research participation website and received course credit for participation. Participants who were currently involved in a committed relationship were excluded. A total of 152 undergraduate students participated in this study. Expectancy manipulation Participants were given different background information and instructions, depending on the experimental group to which they had been assigned. Participants in the high expectancy condition were told that people can easily detect the pheromones of others and that pheromones are an important component of attraction in humans. In the low expectancy condition, participants were told that most people cannot detect the pheromones of others and that pheromones do not seem to influence attraction in humans. Motivation manipulation

Hypotheses This study has three central hypotheses: (a) motivation leads to greater attention to stimuli, (b) the relationship between motivation and placebo response is mediated by attention and (c) expectancy positively influences placebo response, independent of attention. We manipulated both motivation and expectancy, resulting in a 2 (motivation: high or low) × 2 (expectancy: high or low) crossed design. These hypothesised results are consistent with a strong interpretation of the motivation-attention model in which only motivation influences attention. It is also possible that expectancy would have a small influence on attention. In this more moderate interpretation of the model, motivation would have the largest influence on attention and expectancy would exert an influence, but to a lesser degree. It is also reasonable to assume that when both expectancy and motivation factors are high, placebo effects are maximised, an assertion that has

The desire to meet a compatible match was triggered in the high motivation condition. The researcher informed participants that the results of a compatibility survey they filled out at the beginning of the session would be used to “match” them to members of the opposite sex (participants who identified as homosexual on the demographics questionnaire were told the matches were of the same sex). Participants were told that they would be rating the pheromone sample of their selected match and three other randomly chosen samples. In the high motivation condition, the researcher informed participants that if they found the scent of their match to be most pleasing, indicating compatibility with their match, they would have the opportunity to return to the study at a later date along with their match to participate in a second phase of the study together. In the low motivation condition, the researcher told participants that the data collected in this study were for academic purposes only, the identities of their match © 2014 International Union of Psychological Science

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would not be revealed, and that they would not have the opportunity to meet their potential match. Placebo substance Following the procedure used in pheromone research, the placebo sample consisted of water slightly scented by cologne (Filsinger et al., 1985). In preparing the substance, five drops of unisex cologne was added to a 2 l bottle of water. Thus, the overall effect of scent was very slight. The placebo substance (identified as a pheromone to participants) was identical for all four experimental groups. Placebo response Desirability rating of chosen scent Participants rated each of the four samples on the following bipolar dimensions: unattractive–attractive, unsexy–sexy and unarousing–arousing. Each scale had a “neutral” midpoint. Following the study, we translated the ratings to numerical data ranging from 1 (unattractive) to 9 (attractive). The sum of the numerical ratings of attractiveness, sexiness and arousal was averaged to obtain an overall rating of desirability for each of the four scents. Cronbach’s alpha values >.85 for each scent rating provided support for the use of an overall construct of “desirability.” The sample chosen by participants as the most desirable sample was used to define placebo response. Variability in ratings Placebo response was also assessed as the variability (SD) in ratings of desirability of the four samples. Given that there were no actual differences in the samples, greater variability in desirability ratings of these samples should indicate greater placebo response. Attention Assessment time We defined attention as the total amount of time it took for participants to complete the entire rating task. The time began once participants were instructed to start the rating task and ended when participants completed their ratings for all four samples and indicated to the experimenter that they were finished with the task. Number of assessments We also defined attention as the number of times participants smelled each sample. Because the samples were © 2014 International Union of Psychological Science

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applied to separate surgical masks, participants had to raise the mask to their nose in order to make assessments. Distinct sniffs were identified when participants removed the mask at least 2 in. from the face and reapplied the mask to make another assessment. Social desirability A measure of social desirability was included in order to control for potential responding intended to perceive or present one’s self in a favourable light. The Crowne-Marlowe Social Desirability Scale consists of 33 true/false questions and is a commonly used measure of social desirability. Items include a wide variety of behaviours, both desirable (e.g. no matter who I’m talking to, I’m always a good listener) and undesirable (e.g. I can remember “playing sick” to get out of something). Internal consistency has been found to be adequate, with Cronbach’s alpha values ranging from .70 to .77 (Crino, Svoboda, Rubenfeld, & White, 1983). Test–retest reliability over a period of a month was found to be high (r = .86; Crino et al., 1983). Tests of validity that demonstrated positive correlations have been found between social desirability and positive self-evaluations. Procedures Participants who met inclusion criteria were scheduled to meet individually with one of five research assistants. When participants first reported to the lab, they filled out a questionnaire battery containing a personality inventory, relationship attitudes scale, optimism scale, social desirability scale and demographic questionnaire. The researcher informed participants that the results of this “compatibility” survey would be used to “match” them to a member of the opposite sex (or same sex if homosexual). The primary purpose of administering this personality and attitudes assessment battery was to increase the believability of the study design; each of these surveys are face valid measures and would appear to students as a valid means of matching them with potential matches. Following the completion of the assessment battery, the researcher conducted the expectancy manipulation, followed by the motivation manipulation (both described above), by communicating to participants different information regarding the nature of pheromones and the purpose of the experiment. Next, the researcher set up the pheromone rating task. Prior to study initiation, we prepared a large container of the placebo pheromone substance to be used throughout the duration of the study. In advance, dozens of small individually labelled vials had been filled with the substance, to represent the pheromone samples collected from other students. In view of the participant, the researcher selected four vials containing placebo pheromone samples.

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Participants were told that they would be rating the pheromone sample of their selected match and three other randomly chosen samples. The researcher then drew samples from each vial with a medicine dropper and applied the sample to a surgical mask. Research assistants wore lab coats and latex gloves when preparing the samples. The purpose of creating this lab environment was to increase the believability of the task. The researcher placed four masks, each representing one of the samples, on a table in front of the participants. The researcher then placed one desirability rating card in front of each of the masks. The researcher explained the bipolar desirability rating scales to the participant and asked if they had any questions. Participants in all groups were told to take as much time as they needed on these tasks and that they may smell each sample as many times as they needed in order to make their best assessments. They were asked to make their final ratings of samples only when they felt that they had had sufficient time to assess each sample. When the participant began the task of rating the samples, the researcher began timing. During this portion of the procedure, the examiner was seated across the table from the participant. In order to provide the most unobtrusive means of assessment, time was measured using a stopwatch on a cell phone set to the silent setting, which was placed on the experimenter’s lap. As the participant performed the rating task, the research assistant discreetly recorded each time the participant assessed a sample. So as to not influence or disrupt the participant during the rating task, the researchers were instructed to appear busy during this time by quietly reading and organising documents. All research assistants underwent two training sessions and demonstrated proficiency in delivering study procedures prior to beginning work with participants.

comparison for another treatment, a trend that may result from a more careful consideration of factors known to increase placebo effects in experimental studies of placebo (Price et al., 2008). Thus, given a general range of effect sizes in experimental placebo studies of .51 to .95, a conservative estimate of effect size would be at the low end of this range of values (an effect size of about one half a standard deviation; Price et al., 2008). With a power of .80 and an effect size of .50, a total sample size of 75 is needed, indicating that this study is sufficiently powered.

Power analysis

Analysis of hypothesised effects

Studies that examine the mechanisms of placebo responding, as in this study, have been found to have larger effect sizes than those that use a placebo as a control group

To examine the influence of the expectancy and motivation manipulations on mediating and outcome variables, we conducted a series of 2 (high, low expectancy) × 2

RESULTS Study variables and sample characteristics A total of 152 undergraduate students participated in this study. Seventy-one percent of the sample was female; the majority of the participants reported their ethnicity as White (69%), followed by African American (13%), Asian American (7%), Hispanic American (3%) and other (8%). Ninety-four percent reported a heterosexual orientation, followed by homosexual (3%) and bisexual (3%). Most participants (75%) were in their freshman or sophomore year at the university. Mean and standard deviation values for all study variables, by experimental group, are listed in Table 1. Pearson correlations among primary study variables are reported in Table 2. Skewness and kurtosis statistics indicated that the distributions of a few variables displayed significant skewness and kurtosis. Logarithmic transformations successfully corrected data distributions problems, but did not affect primary results or data interpretation. Results reported in this article are based on non-transformed data.

TABLE 1 Mean and standard deviation values of primary study variables by experimental group Experimental group High/High Low/Low Low Motivation/High Expectancy High Motivation/Low Expectancy Total

Mean SD Mean SD Mean SD Mean SD Mean SD

Number of assessments

Assessment time

Desirability of chosen scent

Variability in scent ratings

13.03 8.827 9.49 6.008 10.58 5.612 14.97 9.573 11.98 7.894

176.71 89.877 127.44 68.179 146.89 62.252 172.14 85.950 155.50 79.139

6.4430 1.59310 5.8145 1.24430 5.7632 1.61758 6.4414 1.16084 6.1114 1.44277

1.3784 .86112 .9080 .78081 1.0152 .71780 1.2034 .71640 1.1243 .78523

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TABLE 2 Pearson correlations among primary study variables Number of assessments

Assessment time

Desirability of chosen scent

Variability in scent ratings

1 .70** .33** .20*

1 .44** .24**

1 .61**

1

Number of assessments Assessment time Desirability of chosen scent Variability in scent ratings

6.8

Desirability Ratings by Group 2

Variability in Scent Ratings by Group

6.6 6.4

Hi Mot, Lo Exp

Hi, Hi

6.2 6 5.8

Lo, Lo

Lo Mot, Hi Exp

5.6 5.4 5.2 5

Variability in Scent Ratings

Desirability Rating of Chosen Scent

*Correlation is significant at the .05 level (two-tailed). **Correlation is significant at the .01 level (two -tailed).

1.5 Hi Mot, Lo Exp Hi, Hi Lo Mot, Hi Exp

1 Lo, Lo

Group

0.5

Figure 1. Rating of the placebo outcome “desirability rating of chosen scent” by experimental group. *Error bars represent 95% confidence levels.

(high, low motivation) analyses of variance (ANOVAs). In order to test our first hypothesis, which predicted motivation would lead to greater attention, ANOVA analyses were conducted for each measure of attention, number of assessments and assessment time, with motivation and expectancy experimental groups and an experimental group interaction term entered as predictors. Motivation significantly influenced number of assessments, F(2, 149) = 10.15, p < .01, and assessment time, F(2, 149) = 8.82, p < .01, p < .01 (Figures 1 and 2). Thus, participants in the high motivation conditions displayed greater attention and the first hypothesis was supported. Expectancy did not influence either attention variable, number of assessments, F(2, 149) = .12, p < .73 or assessment time, F(2, 149) = .92, p < .34. Additionally, motivation (but not expectancy) predicted both measures of placebo response, variability in scent ratings and chosen scent, such that those in the high motivation group had greater placebo response (Table 3). No significant experimental group interactions emerged on any of the outcomes examined. The second hypothesis posited that attention would mediate the relationship between motivation and placebo response. Traditionally, the multiple regression approach proposed by Baron and Kenny (1986) accompanied by the Sobel test of significance has been used in testing mediation effects. However, it has been argued that such an approach lacks power to detect an effect. An alternative test of mediation has been proposed that does not have a normality assumption, reducing likelihood of a Type II error (MacKinnon, Lockwood, Hoffman, West, & Sheets, 2002). This approach calculates confidence © 2014 International Union of Psychological Science

Group

Figure 2. Rating of the placebo outcome “variability in scent rating” by experimental group. *Error bars represent 95% confidence levels.

intervals for the indirect effect, with a significant mediated effect indicated by a confidence interval that does not contain 0. Confidence intervals can be computed by entering unstandardised regression coefficients and respective standard error values into a downloadable program, Prodclin, for testing mediation effects (MacKinnon, Fritz, Williams, & Lockwood, 2007). Four tests of mediation were conducted utilising this approach and all four mediated effects were found to be significant. Confidence intervals for the indirect paths (with manipulated motivation as a predictor) were as follows: indirect path with mediator “assessment time” and outcome “chosen scent” (.09, .46), indirect path with mediator “assessment time” and outcome “variability in scent ratings” (.01,.18), indirect path with mediator “number of assessments” and outcome “chosen scent” (.07, .39), and indirect path with mediator “number of assessments” and outcome “variability in scent ratings” (.01, .15). Please refer to Figure 3 for a graphical representation of the mediational paths. Lastly, the third hypothesis, which predicted that expectancy would influence placebo response, independent of attention, was not supported. Results of the ANOVA indicated that expectancy did not influence either of the placebo outcome variables, “chosen scent,” F(2, 149) = .01, p < .91, or “variability of scent ratings,” F(2, 149) = 1.27, p < .26. Furthermore, there was no Motivation × Expectancy interaction effect on either of the placebo response variables, “chosen scent,” F(2, 149) = .01, p < .91, or “variability in scent ratings,” F(2, 149) = .07, p < .79 (Table 3).

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TABLE 3 F and p-values of 2 × 2 ANOVAs testing for effects of motivation (high/low) and expectancy (high/low) experimental group on placebo response and mediating variables

Motivation group (1 = high motivation) Expectancy group (1 = high expectancy) Motivation × Expectancy group interaction

Assessment time

Number of assessments

Desirability of chosen scent

Variability in scent ratings

8.82, p < .01** .92, p < .34 .352, p < .55

10.15, p < .01** .12, p < .73 1.49, p < .22

8.05, p < .01** .01, p < .91 .01, p < .91

6.92, p < .01** 1.27, p < .26 .07, p < .79

*Correlation is significant at the .05 level (two-tailed). **Correlation is significant at the .01 level (two-tailed).

Number of Assessments .25**

.29**

Motivation

Desirability Rating of Chosen Scent .23**

(.16)

Figure 3. Standardised regression coefficients for the relationship between motivation and placebo response (i.e. desirability rating of chosen scent), as mediated by attention (i.e. number of assessments). The standardised regression coefficient between motivation and placebo response controlling for attention is in parentheses. **p < .01.

In conclusion, regression tests of mediation indicated that “number of assessments” and “assessment time” mediated the relationship between motivation and the outcome variables “chosen scent” and “variability in scent ratings.” Thus, motivation led to greater attention as measured by greater time engaging in the scent rating task and greater number of ratings made. Attention, in turn, led to greater placebo response as measured higher desirability ratings of the chosen scent and greater variability in the scent ratings. Inconsistent with hypothesised effects, expectancy did not influence placebo response. Social desirability The Crowne-Marlowe Social Desirability Scale (M = 16.7, SD = 5.1) had a Cronbach’s alpha of .71, consistent with reliability values reported in other studies (Crino et al., 1983). When controlling for social desirability, the motivation experimental group remained a significant predictor of both primary dependent variables, chosen scent, β = .16, t(148) = 1.97, p < .05, and variability of scent ratings, β = .19, t(148) = 2.31, p < .02. Manipulation check We created a 20-item manipulation check measure for the motivation and expectancy manipulations that included face valid items of motivation and expectancy (e.g. I think that the pheromones will influence my attractiveness ratings). We piloted an abbreviated version of this measure

and found the expected differences by experimental group. However, in this study (with the full 20-item measure), we found higher reported placebo expectations in the high expectancy experimental group (M = 3.7, SD = .4) than the low expectancy group (M = 3.4, SD = .6), F(1, 150) = 6.9, p < .01, but no difference in self-reported motivation by motivation experimental group, F(1, 150) = 1.52, p < .21. Cronbach’s alpha values for the 10-item expectancy and 10-item motivation measures were .82 and .80, respectively. Experimenter effects Five research assistants conducted the experiments and were not informed of the research hypotheses. One-way ANOVA analyses revealed no differences by experimenter on any of the primary study variables: chosen scent F(4, 147) = .54, p < .75, variability of scent ratings, F(4, 147) = .44, p < .82, assessment time, F(4, 147) = .54, p < .75 and number of assessments, F(4, 147) = 1.48, p < .20. DISCUSSION To date, motivational influences have not been widely studied in relation to placebo responses, despite the literature presenting motivation as instrumental in shaping various perceptual experiences (Van Damme et al., 2010; Vase et al., 2004). This study sought to clarify the role of motivation and expectancy in placebo responding, examining attention as a mediating variable. We proposed a model in which motivation, causing increased attention to placebo-relevant stimuli is the main driver of placebo process, and expectancy, informing of possible interpretations, helps to define the nature and type of placebo effect observed. As hypothesised, there was a main effect for motivation on both measures of placebo response. Thus, those participants more motivated to respond to the scent of a match found the scent of the chosen sample to be most pleasing and displayed greater variability in the ratings of the four samples. Inconsistent with hypotheses, placebo outcomes were not influenced by the expectancy manipulation in this study. This study also identified an important mediating variable in placebo and suggests that a motivation-attention © 2014 International Union of Psychological Science

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model is a meaningful way to conceptualise placebo change. As hypothesised, both measures of attention mediated the relation between motivation and placebo response. Those participants who were more highly motivated to respond to placebo engaged in a greater number of scent assessments for a longer period of time, which in turn, led to greater placebo response. It is inferred that the greater focus on and attention to the “pheromones” displayed in more motivated participants provided the platform for placebo responses to develop. The influence of motivational factors on feelings of attraction and arousal provides initial evidence that a motivation-attention model of placebo may be applicable to different types of placebo responses, including scent and physical attraction. Although there was an effect of motivation on attention, we cannot rule out the possibility that expectancy forces may also have an effect on attentional processes. It may be that this paradigm produced a less than optimal manipulation of expectancy (a thought we return to later in this discussion section), thus precluding us from observing expectancy effects on the mediating and outcome variables. Thus, the results of this study do not discount the role of expectancy, but rather underscore the important role of motivation in producing placebo effects. Additionally, it is possible that expectancies developed independently of the expectancy manipulation. As discussed in the introduction of this article, motivational and expectancy forces may be characterised by bidirectional influences; if a participant is highly motivated for a placebo to work, this may influence their expectation of placebo benefit, and vice versa. In the present study, highly motivated participants may also have developed placebo-related expectancies, which we were unable to detect in this study. The motivation-attention findings of this study are consistent with models of perception that propose that motivation to observe or experience a desired state can influence the sensations, emotions and physiological input we attend to, altering our overall perceptual experience (Van Damme et al., 2010). Applied broadly, this motivation-attention model may help to explain the presence of placebo responses across a wide range of disciplines. For example, both perception of pain and benefit from placebo analgesia are known to be influenced by many cognitive-evaluative, affective-motivational and attentional factors (Van Damme et al., 2010; Vase et al., 2004). The characterisation of pain as an overall perceptual state impacted by both nociceptive information from the pain site and psychological factors such as attention to pain, goal for pain reduction and mood, provides an illustration of how placebo factors, broadly defined, may impact our everyday experiences. Examining the applicability of this motivation-attention model to other areas of placebo responding, such as pain perception, will provide © 2014 International Union of Psychological Science

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important insights into the various pathways involved in placebo change. Understanding the mechanisms by which placebo is produced also has implications in clinical settings, where placebo is believed to play a role in producing treatment effects. If greater attention to signs of improvement is the process through which placebo is produced, clinicians may be able to increase treatment effects not only by increasing motivation or expectancy to improve, but also by encouraging patients to monitor themselves for signs of improvement. It is true that greater self-monitoring or symptom focus can exacerbate certain conditions, such as pain, in some contexts (Van Damme et al., 2010). However, it might also be the case that orienting a patient to signs of improvement instead of distress, would facilitate, rather than impede, the therapeutic process. Intervening at the level of this attentional mediating variable may help clinicians to maximise placebo factors, thereby enhancing treatment effects. Limitations and suggestions for future research The current study utilised a novel approach to the study of placebo that appeared to be very engaging to participants, an observation that was supported in informal follow-up interviews with participants and by the large effects for the motivation manipulation. Additionally, no experimenter effects were observed, providing some evidence that the protocol may be less sensitive to the influences of demand characteristics. This study demonstrated that assessing placebo responses in feelings of attraction and arousal, sensations that require a degree of introspection and interpretation of bodily cues, provides a useful test of placebo models. Moreover, the behavioural measurement of attention outlined in this study was found to be an effective and easily executed method for assessing the attentional processes involved in placebo change. This protocol would likely be a good paradigm for the future study of placebo mechanisms, although efforts should be made to address what may have been a less than optimal manipulation of expectancy. Expectancy effects vary by study, and recent studies have similarly observed discrepant findings for expectancy influences (Gaitan-Sierra & Hyland, 2013). This study followed a standard procedure for manipulating expectancy in placebo research, where differing levels of expectancy are communicated verbally to participants. However, it is possible that this method does not always have the power to maximise and minimise participants’ expectations. Although participants often report expectations consistent with manipulations, this does not indicate how strongly or confidently they hold these beliefs. Perhaps manipulating expectancy through a behavioural task (e.g. providing fake feedback to participants regarding their ability to identify pheromone scents) would produce a

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more powerful manipulation. New methods to manipulate expectations should be explored that do not rely on the traditional verbal inducement of expectations common to placebo research. Future research should seek to examine placebo and placebo mediators on multiple dimensions. For example, although it is the author’s belief that a major strength of this study lies in the behavioural assessment of the variable “attention,” the introspective process involved in biased attention to and interpretation of internal stimuli characteristic of motivational theories of perception can only be inferred. This makes it more difficult to rule out other potential explanations for observed findings, an issue common to placebo research (Geers et al., 2005), and a limitation of this work. Placebo studies have observed that outcomes do not always converge on different “levels” of measurement, such as behavioural, cognitive and physiological, suggesting that multiple and diverse pathways may be involved in placebo responding (Benedetti et al., 2003). This may also help to explain the failure of the self-report manipulation check to detect a difference between the high and low motivation groups. It is possible that self-report measures of beliefs and attitudes, such as the manipulation check used in this study, may be more suitable for assessing cognitive expectations in placebo. It is less clear whether or not this is appropriate for measuring motivational forces in placebo. It would be prudent for researchers to consider these methodological issues in future study of placebo. More in-depth assessment of placebo variables may involve measurement on multiple dimensions or with new procedures. For example, techniques such as eye movement tracking of visual attentional bias common to addiction research (Mogg, Bradley, & Field, 2003) or functional magnetic resonance imaging (fMRI) of placebo-induced pain processing (Wagner et al., 2004) may be useful assessment tools in some settings. Convergence of placebo responses on multiple levels (e.g. self-report, behavioural and physiological) would provide important information about underlying mechanisms. In future research, these measurement and design considerations will allow for clearer tests of current models and provide a more complete understanding of the processes involved in placebo change. Manuscript received January 2014 Revised manuscript accepted April 2014 First published online May 2014

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