Science + Technology

Belief in Placebo Produces Physical Changes in the Brain, UCLA Study Reveals

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Patients with chronic abdominalpain who received daily placebo pills for three weeks experienced not onlyimprovement in their symptoms, but also showed physiological changes in theirbrain structures as well, a new UCLA study reveals.

The study, to be published inMarch in the online edition of the peer-reviewed journal NeuroImage, shows a pathway by which a belief in a placebo producessuch changes in pain symptoms.

"We wanted to see how the beliefleads to the change in pain symptoms," said Matthew D. Lieberman, assistantprofessor of psychology at UCLA and lead author of the study. "This study helpsanswer that question, and also identifies a neural pathway from a region of thebrain associated with placebos and with thinking about emotional experience toa region closely linked to the placebo-related outcome of diminished pain."

The placebo effect is not justpsychological.

"We actually see physical changesin the brain that correspond closely to changes in symptoms that the patientsreport," Lieberman said.

Seventy-one percent of the placebopatients afflicted with irritable bowel syndrome (IBS) reported improvementafter three weeks. The amount of pain relief reported was very similar for IBSpatients who received actual medication to treat the disease, instead of theplacebo pills, Lieberman said.

Neuroimaging scans with positronemission tomography (PET) revealed decreased activity in the dorsal anteriorcingulate of the patients who reported improvement in their symptoms. Locatedin the center of the brain, the anterior cingulate has been implicated in painand the relief of pain.

Why does the anterior cingulatedecrease its activity in response to the placebo? The UCLA research team alsoanalyzed the regions of the brain that become more active after patients takethe placebos — activity that may inhibit theanterior cingulate response. Among patients who reported improvement insymptoms, the researchers detected a substantial increase in activity inanother part of the brain: the right orbitofrontal cortex.

The right orbitofrontal cortex islocated behind the forehead and eyes, and has been associated with thinking inwords about emotional experiences. This region of the brain also is associatedwith inhibiting behavior, impulses, emotions and thought.

"In placebo patients whosesymptoms were improving, the dorsal anterior cingulate decreased — as if wegave them medication that actually reduced anterior cingulate activity — andthe right orbitofrontal cortex increased," Lieberman said. "These changes inthe brain are related; the increase in the right orbitofrontal cortex predictsthe extent to which the dorsal anterior cingulate will become less active.

"These changes tell us that theplacebo affects the dorsal anterior cingulate associated with the experience ofpain, and that this response may be partly a result of placebo-related thoughtsabout the pain associated with orbitofrontal cortex. Our research suggests thatbelief about the effectiveness of the placebo is turning on the right orbitofrontalcortex area, which, in turn, may be shutting off the anterior cingulate to somedegree."

Theresearchers studied 52 patients with IBS, of whom 23 received daily placebosfor three weeks. The patients completed a daily diary of symptoms, starting aweek before the placebo treatment, and PET neuroimaging tests were performedbefore and after the three weeks of treatment to monitor changing brainactivity of the patients.

Lieberman's co-authors are Johanna Jarcho, agraduate student in his laboratory; Emeran A. Mayer, director of UCLA's Center for Neurovisceral Sciences andWomen's Health, and professor of medicine, physiology and psychiatry at theDavid Geffen School of Medicine at UCLA; Steven Berman, brainimaging head in UCLA's Neuropsychiatric Institute and Brain Research Institute; Bruce D.Naliboff, a clinical professor in UCLA's department of psychiatry andbiobehavioral sciences; Brandall Y. Suyenobu, a researcher in UCLA's Brain Imaging Core of the Center for Neurovisceral Sciencesand Women's Health; and Mark Mandelkern, a UC Irvineprofessor of physics and radiological sciences.

The research was supported bygrants from the National Institute of Diabetes and Digestive and KidneyDiseases and the National Institute of Mental Health.

-UCLA-

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