Placebo treatment can alter primary visual cortex activity and connectivity
Introduction
Brain imaging investigations have shown that the viewing of affective, relative to neutral, pictures provokes increased activation of visual cortex areas (e.g., Britton et al., 2006, Sabatinelli et al., 2007). For example, when participants look at disgusting scenes compared to neutral scenes, this not only activates limbic regions, such as the insula, and the amygdala, but several visual areas located in the occipital, parietal and inferior temporal cortex (e.g., Schienle et al., 2002).
Models of visual emotional perception suggest that the amygdala is central for the initiation of increased extrastriate cortex recruitment. Sabatinelli et al. (2007) demonstrated that during affective picture processing, increases of hemodynamic responses in the occipital cortex were preceded by activation changes in the amygdala. This sequence supports the view that information on the emotional significance of stimuli is first identified in the amygdala and then transferred to the visual association cortex. This process serves motivated attention which allows enhanced perceptual processing of salient and survival-relevant visual information in the environment (Bradley et al., 2003).
Besides this bottom-up-regulation, top-down modulations of visual and affective processing systems have been described. For example, amygdala as well as visual cortex activity during affective picture processing can be altered via cognitive control strategies (e.g., Banks et al., 2007, Goldin et al., 2008). Reappraisal (the conscious attempt to view emotional scenes in a detached way) decreased amygdala activation and increased activation in lingual and angular gyri (e.g. Goldin et al., 2008). Also, reappraisal was able to change functional connectivity between prefrontal cognitive control areas, the amygdala and areas involved in visual attention, such as the inferior parietal cortex (Banks et al., 2007).
Whether automatic emotion regulation strategies are also able to modify amygdalar-occipital activity and connectivity has not been studied thus far, and therefore was the goal of the present study. As a method to initiate unconscious emotion regulation, we chose placebo treatment. The most widely studied placebo phenomenon in neuroimaging research is placebo analgesia, where an inert substance (i.e., a pill filled with sugar) is administered with the verbal suggestion that it is a pain medication. According to Wager (2005), a placebo primarily affects expectancy and appraisal, two related processes crucial in determining the subjective pain experience. In the present investigation, we studied if a ‘disgust placebo’ (an inert pill which was presented to the recipient with the instruction that the substance efficiently reduces disgust symptoms) is able to alter (extra)striate cortex activation during visual emotion elicitation. Moreover, we conducted psychophysiological interaction (PPI) analyses in order to explore functional connectivity between visual cortex areas and brain regions involved in disgust processing (amygdala, insula). We reanalyzed data from a previously published study (Schienle et al., in press), where the administration of the mentioned disgust placebo had provoked a marked decrease in experienced disgust and insula activation during the presentation of disgusting pictures. Interestingly, this placebo had not evoked neural changes during the presentation of fear-relevant pictures, which constituted a second affective condition in the experiment. Thus, the explicit verbal suggestion of disgust reduction had induced an emotion-specific change of brain activation.
We now tested the hypothesis that the disgust placebo (a positive expectation concerning disgust relief) is not only able to specifically change activation and connectivity in brain regions implicated in affective processing, but also in primary and secondary visual areas.
Section snippets
Participants
Thirty-four right-handed, healthy women (mean age = 23.9 years, SD = 4.0) participated in this study. All participants had a high school diploma and 91% were students. The sample had been restricted to females as there are significant sex differences in disgust proneness (Schienle et al., 2002). All participants were free from mental disorders, medication, and somatic problems as assured by the Brief Symptom Inventory (Derogatis, 1993). Written informed consent was obtained from all subjects. The
Affective ratings
The disgust ratings for the Disgust pictures were more than halved in the placebo condition (no-placebo: M = 6.53 (SD = .29); placebo: M = 2.50 (SD = .24), t(33) = 11.70 (p < .001). The fear ratings for the Fear pictures were also reduced (no-placebo: M = 6.12 (SD = .34), placebo: M = 4.09 (SD = .33), t(33) = 4.75 (p < .001). Fear and disgust ratings for the NEUTRAL pictures did not differ between the placebo and no-placebo condition (both p > .16). All participants were convinced that they had received active treatment.
Discussion
We demonstrated that a ‘disgust placebo’ reduced disgust symptoms as well as (extra)striate cortex activation during visual emotion elicitation. Whereas modulatory placebo effects on the activity of the visual association cortex (Petrovic et al., 2005) have been reported before, this is the first study to show that a pharmacologically inactive substance coupled with a positive suggestion of symptom reduction is able to change activation of early visual areas.
Previous neuroimaging studies on
Conclusion
We demonstrated that a placebo can alter basic perceptive processes during affective picture viewing. We administered a silica-filled capsule together with the positive suggestion that this treatment is able to effectively ease disgust symptoms. The placebo reduced experienced disgust as well as activation of the striate cortex, which showed lowered connectivity with limbic regions such as the amygdala and insula. Our data suggest that placebos not only exert their effects via emotion
Acknowledgments
The authors declare no conflict of interest.
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2018, NeuroImageCitation Excerpt :After the NF training, the connectivity measures were comparable between placebo and non-placebo groups. In line with our findings, prior studies also showed that a placebo intervention can affect brain activity (Beauregard, 2007; Meyer et al., 2015; Schienle et al., 2014a, 2014b; Volkow et al., 2006; Wager et al., 2011; Wager, 2005). For instance, Meyer et al. (2015) found a placebo intervention to increase brain connectivity between frontal and more posterior brain areas.
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2018, International Journal of PsychophysiologyCitation Excerpt :Those, given positive information showed faster reaction times without reduction of detection accuracy, while those in the nocebo condition performed worse. Other studies demonstrated that placebo/nocebo-related expectations were able to alter visual exploration behavior (Schienle et al., 2016) as well as activation in brain areas implicated in visual perception (Schienle et al., 2014; Höfler et al., 2018). In an eye-tracking study by Schienle et al. (2016), the participants viewed disgust eliciting images once with, and once without a ‘disgust placebo’ (inert pill administered with the verbal suggestion of an anti-nausea drug).