Context Interventions: Social Modeling and Initial Treatment Experience

In this experiment, the investigators study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects. Specifically, the investigators examine the separate and joint effects of two of the most powerful context interventions: Social modeling-observing someone else being effectively treated-and prior treatment success or failure experiences. Participants will be randomized into 4 groups (Social modeling: observed success vs. observed failure and Conditioning: experienced success vs. experienced failure). The objectives are to investigate the placebo effect on pain relief and aversive image stimuli between and within-subjects. Each group will undergo a behavioral induction phase, fMRI placebo test phase, and an identical 3-month follow up fMRI placebo test phase. Follow-up assessment will provide some of the first evidence on predictors of the durability of placebo and context interventions.

Background:

Humans are highly social creatures, and others' behavior and experiences can have profound effects on symptoms, physiology, and behavior. Social modeling-watching a similar other experience treatment benefits-may also strongly enhance placebo effects and their durability over time, particularly when combined with other context interventions. Social influences can affect core motivational circuitry (e.g., nAC and amygdala), shape learning trajectories, and appears to have distinct mechanisms from other (e.g., conditioning) manipulations. Their impact on brain mechanisms of placebo has not been studied. Likewise, initial perceived treatment success or failure can powerfully shape learning trajectories and placebo analgesia. Initial failure experiences with a treatment type (e.g., pill) may explain some of the treatment failures in studies that (a) attempt to wash out placebo responses with ineffective pills before starting verum drug, or (b) re-randomize non-responders to different pills, as in the STAR\*D antidepressant study. But the effects of initial success/failure experiences on the brain mechanisms of placebo effects have not been studied.

Design:

In an initial observation phase, participants will watch a video of another participant ("demonstrator") undergoing the baseline assessment and placebo test procedure. Next, participants will undergo a conditioning phase. The intervention is a 2 x 2 factorial between-groups manipulation (N = 30 per group) of social modeling (Observed treatment success vs. failure) and participants' initial success experience (Experienced success vs. failure). Thus, the demonstrator will either show strong signs of pain relief during placebo (Observed-Success condition) or no signs of relief (Observed-Failed treatment). During the conditioning phase, all participants will experience high-intensity heat before placebo treatment and then either low-intensity heat after application of a placebo cream, as in the investigator's and others' past work, creating experience of pain relief (Experienced-Success condition) or they will not experience relief (i.e., temperatures will not be lowered; Experienced-Failed treatment). In a subsequent fMRI test phase, participants experience painful heat and aversive IAPS images (as a transfer/specificity test) during fMRI, on skin sites treated with Control and Placebo creams, in a Control -\> Placebo -\> Control block design as in past research. Finally, a 3-month follow-up fMRI test phase, without additional observation or conditioning, will assess durability of brain and behavioral placebo effects.

Eligibility Criteria:
Inclusion Criteria:

* No current psychiatric or major neurological diagnosis
* No reported substance abuse within the last six months
* Capable of performing experimental tasks (e.g., are able to read, able to cooperate with fMRI examination)
* Fluent or native speakers of English
* No current or recent history of pathological pain or reported neurological disorders
* Abstained from alcohol and substance use for 48 hours
* Provided informed consent
* Passed fMRI screening test

Exclusion Criteria:

* Current presence of pain
* Current or past history of primary psychiatric disorder
* Current or past history of psychoactive substance abuse or dependence
* Dementias
* Movement disorders except familial tremor
* CNS infection
* CNS vasculitis, inflammatory disease or autoimmune disease
* CNS demyelinating disease (e.g. multiple sclerosis)
* Space occupying lesions (mass lesions, tumors)
* Congenital CNS abnormality (e.g. cerebral palsy)
* Seizure disorder
* History of closed head trauma with loss of consciousness
* History of cerebrovascular disease (stroke, TIAs)
* Abnormal MRI (except changes accounted for by technical factors or UBOs)
* Neuroendocrine disorders (e.g., Cushings disease)
* Uncorrected hypothyroidism or hyperthyroidism
* Current or past history of cancer
* Recent history (within two years) of myocardial infarction, severe cardiovascular disease, or currently active cardiovascular disease (e.g. angina, cardiomyopathy)
* Uncontrolled hypertension or hypotension
* Chronic pain syndromes
* Chronic fatigue syndromes
* Subjects unable to tolerate the scanning procedures (e.g., claustrophobia)
* Prior treatment within the last month with any of the following: antidepressants, mood stabilizers, glucocorticoids, opiates
* Prior treatment with any of the following: antipsychotics, isoniazid, centrally active antihypertensive drugs (e.g. clonidine, reserpine)
* Metal in body or prior history working with metal fragments (e.g., as a machinist)
* Pregnancy
* Any other contraindications for MRI examination (e.g., metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body)
* Claustrophobia