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Researchers Take Neuro-Snapshots of the Brain's Awesome Placebo Response

Adding yet more science to the realm of sham medicine.
Image: Carolyn Speranza/Flickr

The placebo effect occupies a peculiar netherworld in contemporary medicine. On the one hand, alt-medicine types—herbalists, acupuncturists, anti-psychiatrists, etc.—are loathe to admit that their product does not have a “real” effect or at least the real effect that they advertise, while, on the other, practitioners of science-/evidence-based medicine aren’t very fond of treatments that are fundamentally dishonest (see: the placebo paradox), or, at the very least, treatments that defer to the relative “black box” of psychology. So the concept just kind of hangs out at the fringe of medical practice, while evidence continues to mount as to its awesome, baffling power.

To tap that power, or to tap it in a way that doesn’t involve “tricking” patients, means getting rid of the black box surrounding its actual physiological basis. If researchers can pin down the neurological functioning behind the placebo effect, it might become possible to exploit it without the intermediary of sham treatment. A study out this week in the Journal of Clinical Investigation describes a crucial step in that direction, identifying, via network modeling and fMRI observations, “a distinct cerebello-limbic circuit” that’s activated in Parkinson’s Disease patients subject to “sham surgery.”


“Blinded” patients that responded favorably to fake surgery showed long-term signs of activation within this network, while patients treated conventionally with psychoactive medication or that experienced further disease progression, showed no activation. This aligns well with the mounting pile of neurological observations characterizing placebo effects in other realms of, mostly, brain disorders. “Several regions contributing to this network have previously been noted to exhibit increases in local activity in response to placebo,” the study notes, pointing to a 2002 study on antidepressant trials. That study found a wide range of neurological activation in patients receiving placebo treatments, including within the subgenual cingulate gyrus, part of the brain's emotional center and a network highly correlated with ratings on the Beck Depression Inventory.

In an email to Motherboard, co-author David Eidelberg notes that this is the first study of its kind to map the placebo response as a whole, at the level of a full network. Previous studies have revealed, "one or more 'fragments' of the network topography but give no info regarding neural activity at the systems [network] level," he says. "This difference in topographic scope is important [because] only measurements of the activity of the overall brain network topography—as opposed to those from single, isolated brain regions—are stable enough for use as quantitative imaging biomarkers in individual subjects."

The current JCI study achieves a more specific and immediate goal, however, than a general neurological exploration of the placebo effect. In evaluating outcomes from surgical interventions in Parkinson’s patients historically, it’s been quite difficult to distinguish between “real” and placebo responses; surgery, after all, is heavy stuff and weighs heavily on the mind. With an open-heart triple bypass operation, doctors know they’ve succeeded because blood is flowing this way instead of that way, but in matters of the brain and behavior, success is a more elusive notion. If it were possible to eliminate study participants that are more susceptible to placebo effects, it should become possible to gather more meaningful results.

So: less wasted time, effort, and misery.

That’s the suggestion behind this week’s study: with close identification of this circuit, researchers should be able to pick out patients with stronger physiological inclinations toward placebo effects. This is an ability that has obvious consequences beyond just Parkinson’s brain surgery; the placebo effect is one of the fundamental barriers to most all medical research and if it were possible to cut back on some of the painstaking effort undertaken to neutralize it, that’s good for everyone.