A group of researchers at Massachusetts General Hospital and Beth Israel Deaconess Medical Center focused on understanding the placebo effect—the gains in health that can occur when patients receive a sham treatment that they believe is real—are trying to unravel the neurobiology of the doctor-patient interaction. They have been putting physicians in scanners and watching what areas of the brain are activated when a doctor provides pain relief to a patient, seeking to understand what intangible aspects of a doctor’s demeanor may lead to better or worse medical care.

The study, published Tuesday in the journal Molecular Psychiatry, found that areas of doctors’ brains involved in empathy and anticipation of pain relief lit up when their treatment alleviated pain. What the researchers still don’t know, however, is whether that brain activation means anything: will a doctor whose brain lights up in a particular way during a patient interaction provide care that leads to better outcomes?

That’s an important question, because at least one study has found that who a patient’s doctor is can matter more than the medication; a study of depressed patients found that who a patient’s psychiatrist was had a larger treatment effect than the drug they were given.

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Outside scientists cautioned that, although the study is interesting, interpretations of such data can be difficult because of the inherent limitations of brain imaging studies.

“You are kind of stuck, in general, with this sort of uncertainty about what’s the real underlying process you’re tapping in to,” said Russell Poldrack, director of the Imaging Research Center at the University of Texas at Austin. “Even if it’s the case when people engage in empathy, that site of the brain area gets turned on, that doesn’t mean when the brain area is turned on it’s necessarily empathy. ... It’s pretty much impossible to make a strong conclusion.”

The researchers acknowledge this is just a first step. They launched the study with the modest intent of seeing whether it was possible to image physicians’ brains while they treated a patient. These provide baseline measurements of doctors’ brains during an interaction, but can't show yet whether those signals are linked to better or worse health care. Ultimately, they hope to use knowledge of the brain activation involved in a successful patient-physician exchange to shape training and policy.

“If we want to in the future be able to train doctors to have a certain interaction style with their patients in order to improve the care, we have to know exactly what it is that’s going on within them,” said Karin Jensen, a research fellow at Mass. General who conducted the research.

The researchers started with the prediction that when doctors administered pain relief to patients, the physicians’ brains would mirror those of patients, with activation of brain areas involved in anticipating pain relief. They also predicted that brain circuits involved in feelings of rewards would be activated when a treatment resulted in successful pain relief. The results largely met their expectations.

They started by demonstrating to 18 doctors a pain relief device they would be using to treat patients. First, the doctors received a painful stimulus of heat applied to their arms. Then, they were told that an electronic wristband would be used to relieve the pain. The wristband didn’t really do anything, but when it was “on,” the researchers turned down the heat so the doctors felt less pain.

Next, after conducting a clinical exam of an actor playing a patient, the doctors were put in a brain scanner that was equipped with mirrors so that they could still see the patient’s face. The patient received the pain stimulus, and doctors were either told to push a button to administer the treatment, or press a dummy button that administered no treatment.

They found that areas of doctors’ brains involved in empathy were active when they watched the patient grimace with pain. Brain circuits that the researchers had seen turn on in patients who were experiencing the placebo effect—expecting pain relief—were active when the doctors were treating their patients, but not when they gave no treatment. Physicians who scored well on a test of their ability to take the perspective of their patient had greater activity in a portion of the brain that is involved in feelings of reward.

It’s an open question whether such research will improve medical care. Will maps showing which brain areas light up in a given laboratory demonstration actually elucidate much about complex social behaviors, much less how to improve them?

The researchers think so. They argue that knowing which circuits turn on in the brain will help shape interaction with patients in productive ways.

“Understanding how bonding is made, how trust is created, compassion is expressed; those are questions we hope that this study has a way of looking at,” said Ted Kaptchuk, director of the Program in Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess.

Still, knowing which bits of brain flash on during an act of compassion will leave them with the challenge of teaching doctors to act more compassionate.