Perhaps nowhere else is the role of cognitive processes on the development of nausea more evident than in the context of expectations. Numerous observations have been made under a variety of nauseogenic circumstances of expectations’ effects on the development of nausea, and on the physiological changes that accompany reports of symptoms. The dramatic impact of placebos on both symptoms and physiological function has been interpreted to be the effect of manipulation of one’s expectations of the effect of a given treatment. It is important to emphasize that placebo effects are not simply matters of symptom perception; they are accompanied by measurable changes in physiological indices of health.

Response expectancy theory attributes the placebo effect to the forming of expectations that an ingested substance will produce both subjective and physiological changes in accordance with the supposed effect of that substance [51]. Response expectancy is defined as the anticipation of the occurrence of nonvolitional, automatic responses. For instance, if an individual expects a treatment to produce relief from pain or any other response that is not under that individual’s direct control, the effect is much more likely to take place than if no such expectation exists. Individuals can learn to expect certain outcomes simply by listening to others’ descriptions of a treatment to be administered or by observing the behavior of others who supposedly have experience with the treatment [52]. Kirsch suggested that the single-most influential determinant of the placebo response is one’s expectation that some change in bodily state will be achieved through the administration of a placebo treatment.

Internal states such as mild nausea tend to be somewhat ambiguous, particularly during the early stages of their development. This ambiguity may underlie the strong association between response expectancy and involuntary, automatic responses to stimuli [51]. A response expectancy may induce a perceptual set that is employed for the interpretation of ambiguous bodily sensations. Once an interpretation has been made that a set of vague physiological sensations is representative of the anticipated condition, an unspecified psychophysiological mechanism is initiated that produces the expected physical symptoms that otherwise may not have developed.

Several studies suggest expectations play a meaningful role in the development of nausea symptoms. Chemotherapy patients exhibit direct relationships between expectations for nausea before their first treatment and nausea that actually develops [53, 54]. In addition, patients who expect nausea side effects of the treatment report significantly more severe nausea than those who do not. Eden and Zuk [55] conducted a study of naval cadets undergoing training on rough seas that often promote the development of nausea and motion sickness. Those provided with a “verbal placebo” that they would not suffer from severe symptoms because of their psychological and physiological profiles developed significantly less nausea than those who were not.

Mearin et al. [56] administered placebos to patients with functional dyspepsia, a disorder marked by abdominal pain or discomfort centered in the upper abdomen and/or nausea, bloating, and early satiety following meal ingestion [13]. The condition lacks a substantiated structural or biochemical explanation but is often accompanied by disturbed gastric motility. After 8 weeks of placebo treatment, scores on a global symptom index were significantly reduced in 80 % of the patients. The reduction in symptoms was accompanied by a return of normal gastric motility. The placebo’s effect on subjective symptoms could not, therefore, be attributed solely to a response bias. In a series of studies exploring the use of acustimulation for the management of nausea and gastric dysrhythmia, significant placebo effects were observed (e.g., [57]).

The idea that the placebo response represents a specific biological phenomenon is based on the assumption that mental experience can somehow affect physiology. According to Fields and Price [58], the administration of a placebo alters the interacting neural representations of memory, environmental context, and specific sensory stimuli. This aggregate of neural activity translates into a subjective experience that simultaneously affects physiology. Indeed, cognitive factors like attribution, belief, desire, motivation, and expectation may be potent mediators of the placebo response [59]. That placebo effects of greater magnitude are achieved by more believable and technically sophisticated agents seems to support this idea. For instance, placebo injections elicit greater placebo responses than placebo pills, and larger pills are associated with stronger placebo responses than smaller pills; the number of pills taken is also directly related to the magnitude of the placebo response [60]. Also, when there is a strong desire for a given treatment to produce a certain effect, as when pain is extraordinarily intense, the placebo effect tends to be augmented.

The results of a study employing the rotating drum in order to induce the nausea of motion sickness demonstrated the powerful effect of placebo-induced expectations on nausea and gastric dysrhythmia [61], albeit in a different manner than what was predicted. All participants were given placebo pills prior to their exposure to the rotating drum, but were led to believe different things about what the effects of the pills would be. One group of participants was led to believe that the pills would essentially prevent the development of nausea, while another was told the pills would actually intensify their symptoms. Surprisingly, nausea was significantly less severe among participants told their experience would be made more unpleasant by the administration of the pills than among participants who were assured that their experience would be relatively innocuous (Fig. 14.2). This reverse placebo effect was also revealed by EGG data that were collected; participants who believed they would not experience nausea developed significantly more gastric dysrhythmia during their exposure to the motion stimulus. These results are consistent with those of Williamson et al. [62], who demonstrated high expectations of motion sickness symptoms produced by a rotating drum to be associated with the inhibition of the development of gastric tachyarrhythmia.

Although the results of Levine et al. [61] did not confirm the hypothesis of a traditional placebo effect, they dramatically demonstrate the ability of expectation to influence nausea. In retrospect, the startling results were not difficult to interpret. It was speculated that participants who were told they should anticipate a sickening ordeal may have experienced something far more innocuous than they had expected. Participants who were led to believe their experience in the rotating drum would be fairly benign due to the pills they were given soon realized it would be much more unpleasant than they came to expect. These important differences may have resulted in very different experiences for these two groups of participants. Those who unnecessarily braced themselves for a torturous ordeal may have been calmed or relaxed by what they experienced, whereas those who expected to feel fine may have been alarmed by or unprepared for what they confronted. These differences may have differentially influenced the development of nausea and gastric dysrhythmia. Presumably, participants in each group experienced the same ambiguous, somewhat unsettling sensations during the early minutes of exposure to the nauseogenic stimulation. Those who were alarmed by the sensations probably interpreted them as relatively severe and may have activated an unspecified psychophysiological mechanism that intensified the nausea and gastric dysrhythmia they were already experiencing. Those who were relieved by the sensations likely interpreted them as relatively mild, thereby leading to the minimization of nausea symptoms.

Expectation appears to have a significant impact on the nausea experienced by cancer patients undergoing chemotherapy as well. Several studies have demonstrated that patients expecting to experience nausea during or after their chemotherapy treatment are more likely to suffer from nausea (e.g., [63]). Anticipatory nausea is experienced by approximately 25 % of cancer patients who had previous treatments during which they experienced nausea [64]. Classical conditioning models have been used to explain the occurrence of anticipatory nausea; neutral stimuli such as the drive to the hospital, and the sights, sounds, and smells of the treatment facility are associated by patients with the chemotherapy agents that are administered. If nausea develops during or after the treatment, the previously neutral stimuli acquire the ability to induce symptoms on subsequent visits to the hospital even before the chemotherapy agent is administered. Levine et al. [65] demonstrated support for this idea in a sample of 49 cancer patients receiving chemotherapy. Both acute and delayed nausea experienced during prior chemotherapy treatments were significant predictors of anticipatory nausea experienced before the next administration. Presumably, patients who suffered from nausea during and/or after earlier treatments anticipated more of the same in the context of subsequent treatments, perhaps because their anticipation induced physiological changes consistent with the development of nausea.

The perception of control may be conceived of as the belief that one has the power to dictate the outcome of a situation. Perceived control over a potentially aversive situation has been repeatedly demonstrated to have a significant favorable impact on an individual’s subjective and physiological response to stress (e.g., [66–68]). It is not entirely clear how perceptions of control minimize stress, but most theorists advocate the position that maintaining a belief that the outcomes one experiences are contingent upon one’s actions allows the person to more effectively cope with and hence reduce the unpleasantness of stress.

Predictability is the capacity to accurately anticipate future events. Many studies have demonstrated the availability of predictive information to diminish the subjective and physiological response to stress as well (e.g., [69, 70]). The ability to foresee how a stressful situation will develop can be advantageous for generating an adaptive coping response; knowing when, and for how long a stressful period will last allows people to prepare themselves to cope more effectively with the stressor. Perhaps more importantly, a sense of predictability allows a person to take comfort in the awareness of when it is no longer necessary to engage a coping response and relax given the absence of a stressor [71]. One feature of the perception of control that might allow it to be effective for reducing stress is its relationship with being able to predict and anticipate the development of a challenging situation. An individual who knows he or she can dictate future events related to a potentially aversive interaction can, by definition, predict the course of those events. The beneficial effect of perceived or actual control on responses to various forms of stress may therefore, in varying degrees, be attributed to the predictability that it provides.

Levine et al. [72] explored the extent to which perceptions of control and predictability could both individually and collectively affect the development of nausea, motion sickness, and gastric dysrhythmia during exposure to a motion sickness stimulus. Perceived control was manipulated by providing some participants with the means to start and, more importantly, stop their exposure to a rotating optokinetic drum at their discretion by simply flipping a switch. Other participants were told that in order to terminate the session if their symptoms became intolerable, they needed to request the drum’s rotation to be stopped by an experimenter from an adjacent room. Predictability was provided with and without control of the motion sickness stimulus. Some participants were informed of the duration of their exposure to the rotating drum and were also given regular updates regarding how much time remained. Although the provision of control of the drum itself made the situation somewhat more predictable, the availability of temporal information made the experience considerably more predictable for some participants.

As predicted, the development of nausea was significantly attenuated in participants given control of the rotating drum, and also in participants given predictability concerning the timing of their exposure (Fig. 14.3). The significant main effects of control and predictability on ratings of nausea suggest that providing participants with the means to start and stop the drum’s rotation and, to a lesser extent, providing them with predictive information about the duration of the drum rotation period was each effective for reducing the intensity of nausea and other symptoms of motion sickness. That the interaction effect of perceived control and predictability on nausea ratings scores was not statistically significant suggests that these protective effects were additive rather than interactive. In other words, perceived control and predictability appeared to act as distinct psychological factors in the attenuation of the subjective experience of nausea. Having both control and predictability appeared to offer the most protection to participants from the development of nausea, but the effect of one did not depend on the availability of the other. The protective effects of control and predictability were also revealed by their influence on gastric myoelectrical activity [72]; gastric dysrhythmias were least evident in those provided with both control and predictability.

That providing individuals with the opportunity to escape from the stimulation that might bring them discomfort results in the experience of less unpleasant consequences makes great intuitive sense. However, it still is not entirely clear why perceptions of control are so valuable in situations like the rotating drum where noxious stimulation must be coped with effectively. One possibility is that control exerts its protective effects against nausea through its ability to reduce stress and anxiety, and the accompanying physiological responses [66, 68]. The issue remains unresolved, though it is likely that through some as yet unspecified psychophysiological mechanism, perceived control motivates an individual to engage in some form of coping, whether active or passive, which adaptively reduces the stress and negative consequences that result from an aversive situation. Explaining predictability’s capacity to provide relief to those enduring stressful conditions is somewhat more intuitive. Knowing exactly when, and for how long a stressful event will take place will certainly facilitate effective coping with the situation. Without such predictive information, coping resources might seem far too scarce to deal with what could go on for a considerable time longer. This sort of thought process might begin a cascade of negative cognitions that could serve to worsen the stressful nature of the situation, both subjectively and physiologically [69–71]. Having the capacity to predict the unfolding of future events may stimulate positive thinking that facilitates successful adjustment to stressors of all kinds, including those that tend to promote the development of nausea.

As mentioned earlier, nausea is often reported by individuals struggling with stress and anxiety. Reports of nausea have been shown to be common among patients with anxiety disorders such as generalized anxiety disorder [73]. Cancer patients with a great deal of anxiety have been reported to suffer from more side effects of chemotherapy, including nausea and vomiting [74]. In a thorough review of the role of anxiety in chemotherapy-induced nausea, Andrykowski [75] concluded that anxiety contributes to the development of both anticipatory and posttreatment nausea.

Gianaros et al. [10] presented participants with two laboratory stressors and evaluated their effects on gastric myoelectrical activity and ANS responses. Both stressors caused an increase in gastric dysrhythmia, an increase in SNS activation, and a decrease in PNS activation. The extent to which SNS activation increased, in particular, was predictive of nausea that developed during subsequent exposure to a rotating optokinetic drum, suggesting that one’s physiological response to stress plays a role in susceptibility to nausea evoked by a motion stimulus.

If stress exacerbates nausea, then efforts to limit stress should presumably reduce the intensity of nausea, or help prevent it from developing. Relaxation has often been demonstrated to have beneficial effects on individuals’ subjective well-being and stress level, and on a variety of health-related outcomes (e.g., [76, 77]). The physiological mechanism that mediates the purported influence of interventions such as mindfulness meditation and progressive muscle relaxation remains elusive, but likely involves the central and autonomic nervous systems. Levine et al. [78] examined the effects of a brief session of progressive muscle relaxation on reports of nausea made by individuals exposed to a rotating drum, and on the development of gastric tachyarrhythmia. Participants assigned to the relaxation group were guided through a 10 min progressive muscle relaxation program prior to their exposure to the rotating drum. As predicted, participants who engaged in the progressive muscle relaxation program prior to their exposure to the motion stimulus experienced significantly less severe nausea (Fig. 14.4). Analysis of the physiological data is ongoing, and may contribute to the elucidation of the physiological mechanism responsible for relaxation’s beneficial effect.

Distraction has been found in many instances to have a beneficial effect on pain; for instance, those who are engaged in a cognitive task that is demanding of one’s attention, or an activity they find interesting and enjoyable tend to report pain as less severe (e.g., [79, 80]). Levine et al. [81] examined the effects of two sorts of distraction on nausea and gastric dysrhythmia induced by exposure to a rotating drum. A randomized, independent-groups design was employed in which 60 participants were assigned to one of three experimental groups. Distraction was manipulated in two ways in an effort to determine whether one is more effective than the other at reducing nausea and its physiological underpinnings. Each was compared to a no-distraction control group. The first version of distraction was a cognitive/attentional distracting task called shadowing that was completed during exposure to the nauseogenic stimulus. Shadowing consists of repeating back the words being read to the participant from a recorded message in a continuous manner. The second version of distraction was an interest/engagement task that combines attentional distraction with a source of emotional enjoyment. Participants in this group were permitted to listen to their favorite variety of music while they were exposed to the rotating drum. It was hypothesized that participants in each of the distraction groups would report less severe nausea and other symptoms of motion sickness than participants in the control group. It was also expected that participants in each of the distraction groups would exhibit less gastric tachyarrhythmia than participants in the control group. Specific differences between the shadowing and music groups were not anticipated, as each distraction manipulation was expected to be effective for reducing nausea.