The placebo effect: advances from different methodological approaches

Abstract

There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.

Figures

Figure 1.

The scheme shows how psychosocial signals including conditioning, verbal and observational cues are detected by the brain, interpreted, and translated into neural inputs crucial to form expectations and placebo responses resulting in behavior and clinical changes (adapted from Colloca and Miller, 2011a).

Figure 2.

Consistent placebo-related neuroimaging findings from 2004 to 2011. A complete list of studies can be found in Wager and Fields (2011). A, Placebo-related decreases during pain, or regions in which placebo-related decreases were correlated with placebo analgesia. B, Placebo-related increases in neuroimaging activity during anticipation or pain, or regions in which placebo-related increases correlated with placebo analgesia. The top rows show individual peak coordinates (for more details, see Wager and Fields, 2011), and the bottom rows show areas activated in at least three separate maps. Note that increases and decreases can be found in the same brain regions, if, e.g., there are consistent increases during anticipation of pain and decreases during pain experience. This is the case with the rostral dorsal cingulate region shown in both maps.