Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data

The brain systems underlying placebo analgesia are insufficiently understood. Here we performed a systematic, participant-level meta-analysis of experimental functional neuroimaging studies of evoked pain under stimulus-intensity-matched placebo and control conditions, encompassing 603 healthy participants from 20 (out of 28 eligible) studies. We find that placebo vs. control treatments induce small, widespread reductions in pain-related activity, particularly in regions belonging to ventral attention (including mid-insula) and somatomotor networks (including posterior insula). Behavioral placebo analgesia correlates with reduced pain-related activity in these networks and the thalamus, habenula, mid-cingulate, and supplementary motor area. Placebo-associated activity increases occur mainly in frontoparietal regions, with high between-study heterogeneity. We conclude that placebo treatments affect pain-related activity in multiple brain areas, which may reflect changes in nociception and/or other affective and decision-making processes surrounding pain. Between-study heterogeneity suggests that placebo analgesia is a multi-faceted phenomenon involving multiple cerebral mechanisms that differ across studies

Interactions in the hedonic experience of touch and emotion : a double-blind placebo-controlled study using intranasal oxytocin

Interpersonal touch is a key means for communicating emotions in humans, and can be a powerful modulator of behavior. Perceived characteristics of the toucher, including his/her personality and emotional state, are among the factors likely to influence the hedonic touch experience in the touchee. The neuropeptide oxytocin (OT) is involved in a range of social interactions, and has been proposed promote prosocial behavior in humans. The present study investigated interactions in the hedonic experience of touch and emotion perception, and addressed the role of oxytocin in these interactions. Thirty healthy individuals participated in a within-subjects placebo-controlled study where central OT levels were elevated through administration of a nasal spray. Participants watched faces with different emotional values while simultaneously receiving socially relevant touch or a control non-social vibratory stimulus on the forearm. After each stimulus pair, they rated characteristics of the faces (perceived anger, happiness, attractiveness and friendliness), or characteristics of the touch (perceived pleasantness and intensity). Throughout the experiment, participants’ pupil responses to the tactile and visual stimuli were recorded as a measure of autonomic nervous signalling. The results revealed that faces were rated as friendlier and less angry when accompanied by touch compared to vibration. Conversely, the reported pleasantness of tactile stimuli increased with happy faces relative to angry faces. OT was not found to increase positive perception of emotional stimuli. In contrast, participants rated angry faces as more angry with OT, supporting a view that its role in human social interactions is more complex than merely promoting positive social behavior

The association between personality traits and placebo effects: A preregistered systematic review and meta-analysis

Placebo effects are ubiquitous yet highly variable between individuals, and therefore strongly impact clinical trial outcomes. It is unclear whether dispositional psychological traits influence responsiveness to placebo. This preregistered meta-analysis and systematic review synthesized the literature investigating the association between personality traits and placebo effects. Based on 19 studies with 712 participants, we performed formal meta-analyses for 10 different personality traits. We did not find evidence of associations between any of these traits and magnitude of placebo effects, which was supported by equivalence tests. Furthermore, we did not find evidence for moderating factors such as placebo manipulation type (Conditioning, non-conditioning) or condition (pain, non-pain). However, the current synthesis was not statistically powered for full inquiry into potential conditional or interactive associations between personality and situational variables. These findings challenge the notion that personality influences responsiveness to placebos and contradict its utility for identifying placebo “responders” and “non-responders”

The Neurobiology Shaping Affective Touch: Expectation, Motivation, and Meaning in the Multisensory Context

Inter individual touch can be a desirable reward that can both relieve negative affect and evoke strong feelings of pleasure. However, if other sensory cues indicate it is undesirable to interact with the toucher, the affective experience of the same touch may be flipped to disgust. While a broad literature has addressed, on one hand the neurophysiological basis of ascending touch pathways, and on the other hand the central neurochemistry involved in touch behaviors, investigations of how external context and internal state shapes the hedonic value of touch have only recently emerged. Here, we review the psychological and neurobiological mechanisms responsible for the integration of tactile "bottom-up" stimuli and "top-down" information into affective touch experiences. We highlight the reciprocal influences between gentle touch and contextual information, and consider how, and at which levels of neural processing, top down influences may modulate ascending touch signals. Finally, we discuss the central neurochemistry, specifically the mu-opioids and oxytocin systems, involved in affective touch processing, and how the functions of these neurotransmitters largely depend on the context and motivational state of the individual.Funding Agencies|Norwegian Research Council (FRIPRO); Marie Sklodowska-Curie Actions, under the COFUND program [240553/F20]</p

Mechanisms of Musical Analgesia

Investigating underlying mechanisms of a pain management treatment, music therapy. Due to their involvement with natural pain processing and analgesia, opioids have been implicated in music-induced pain relief. We explore this link directly by asking, is music-induced analgesia mediated by the endogenous opioid system and is the expectation of pain relief a driving force of this effect? This study investigates a possible neural mechanism underlying a non-drug pain management tool. It also provides placebo-controlled, randomised research to a growing music therapy field

Dynamic brain-to-brain concordance and behavioral mirroring as a mechanism of the patient-clinician interaction

The patient-clinician interaction can powerfully shape treatment outcomes such as pain but is often considered an intangible “art of medicine” and has largely eluded scientific inquiry. Although brain correlates of social processes such as empathy and theory of mind have been studied using single-subject designs, specific behavioral and neural mechanisms underpinning the patient-clinician interaction are unknown. Using a two-person interactive design, we simultaneously recorded functional magnetic resonance imaging (hyperscanning) in patient-clinician dyads, who interacted via live video, while clinicians treated evoked pain in patients with chronic pain. Our results show that patient analgesia is mediated by patient-clinician nonverbal behavioral mirroring and brain-to-brain concordance in circuitry implicated in theory of mind and social mirroring. Dyad-based analyses showed extensive dynamic coupling of these brain nodes with the partners’ brain activity, yet only in dyads with pre-established clinical rapport. These findings introduce a putatively key brain-behavioral mechanism for therapeutic alliance and psychosocial analgesia