Brain Connectivity Can Predict Occurrence of Placebo Effect

by Patrick Yang ’20

Figure 1. Neuroimaging of brain connectivity in the right midfrontal gyrus can predict the occurrence of a placebo effect.


The placebo effect has consistently stumped the scientific community because it provides an effective treatment based on a patient’s belief, rather than a scientific reason. Instead of disregarding the placebo effect, Dr. Pascal Tétreault of Northwestern University and his team aimed to discover the biological context and the predictability of placebo response in chronic pain patients. Since some patients exhibit the placebo effect while others do not, brain structure was specifically examined to predict whether a certain connectivity was inclined to exhibit the placebo effect.

The study was a two-part study which examined 56 patients with knee osteoarthritis who experienced chronic pain. The first study involved a two-week placebo pill trial with 17 patients, while the second involved a three-month randomized trial with 39 patients. The latter study compared the effects of a placebo and duloxetine, a type of painkiller. Prior to both studies, functional magnetic resonance imaging (fMRI) was used to take brain measures and map brain connectivity in order to compare a resting-state fMRI to post-treatment fMRIs. During treatment, fMRI-derived brain connectivity maps of placebo responders and placebo non-responders were compared to not only each other, but also their resting-state connectivity maps.

Approximately half of the patients in both studies experienced placebo-induced analgesia, or pain relief. Comparison of resting-state connectivity maps with maps of placebo responders and placebo non-responders revealed that differences in the frontal lobe, specifically the right midfrontal gyrus connectivity, determined the presence and magnitude of placebo response. The effects of duloxetine also varied among patients, and either enhanced or reduced the predicted effects of placebo response. The efficacy of drug-induced analgesia was attributed to connectivity in the right parahippocampus gyrus.

The conclusion that brain connectivity can predict whether drug or placebo-induced analgesia will occur has significant implications for the treatment of chronic pain. The use of fMRI-derived brain connectivity maps in the clinical setting allows for individualized drug treatment of all patients with chronic pain because an image of a patient’s brain will predict whether a drug is effective. Based on connectivity maps, physicians may be able to predict whether or not a drug will enhance analgesia in their patients, which allows for optimal treatment and removal of the usual trial-and-error process of finding an effective drug.


  1. P. Tétreault, et al., Brain connectivity predicts placebo response across chronic pain clinical trials. PLOS Biology 14, (2016). doi: 10.1371/journal.pbio.1002570.
  2. Image retrieved from:

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