NEW YORK (Reuters Health)—Brain connectivity differences predict placebo responses in patients with chronic knee osteoarthritis, researchers report.
Positive medical responses to placebo treatments are common, but the underlying central nervous system mechanisms remain unclear.
Dr. Marwan N. Baliki and colleagues from the Feinberg School of Medicine at Northwestern University in Chicago used resting-state functional MRI to investigate brain connectivity and its relationship to placebo responses in patients with chronic knee osteoarthritis.
Nearly half of the participants in the first study (8/17, 47%) were classified as placebo responders.
Compared with nonresponders, placebo responders showed significantly higher connectivity from the right midfrontal gyrus to the rest of the brain, the researchers report in PLoS Biology, online October 27.
Placebo responders also showed greater connectivity from the posterior cingulate cortex, anterior cingulate cortex, and the right secondary somatosensory and primary motor cortex.
In subsequent studies, right midfrontal gyrus connectivity differentiated between placebo responders and nonresponders with 95% accuracy.
In contrast, right midfrontal gyrus connectivity did not differentiate between responders and nonresponders to active medication (duloxetine).
Connectivity with the right parahippocampal gyrus, however, predicted active drug responses after accounting for the placebo response.
“By modeling the expected placebo response in subjects receiving active drug treatment, we uncover a placebo-corrected drug response predictive brain signal and show that in some subjects the active drug tends to enhance predicted placebo response, while in others it interferes with it,” the researchers write.
“Together, these results provide some evidence for clinical placebo being predetermined by brain biology and show that brain imaging may also identify a placebo-corrected prediction of response to active treatment,” they add.
Dr. Karin Jensen from Karolinska Institute in Stockholm, Sweden, told Reuters Health by email, “It is fascinating to see studies with more and more detailed knowledge about the neural basis of placebo effects. It was not long ago that placebo effects were commonly seen as a response bias, without any true underlying change in patients’ physiology.”
“However, since the advent of neuroimaging, the neural underpinnings of placebo effects have been elucidated and a new generation of researchers can focus on revealing the complexity of placebo mechanisms, and variations in placebo response, instead of proving that placebo effects are real,” she said.
“I find it intriguing that the authors move between concepts of placebo responses being ‘predetermined by initial brain physiology’ and brain analyses of a single experiment that capture neural processes that fluctuate in matter of seconds during a brain scan,” Dr. Jensen added. “In the future, the temporal domains of placebo responses will hopefully be described in more detail, either by these authors or by other placebo neuroimaging groups.”
“Placebo responses have a representation in the central nervous system and in the future it is possible that a patient’s likelihood to respond to placebo treatment can be predicted in clinical trials, thus changing the way clinical trials are designed and interpreted,” she concluded.
Dr. Baliki and coauthor Dr. A. Vania Apkarian did not respond to a request for comments.
Reference
Tétreault P, Mansour A, Vachon-Presseau E, et al. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials. PLoS Biol. 2016 Oct 27;14(10):e1002570.
