Despite years of study, the placebo effect remains a source of mystery.
Researchers developed a “map” of brain regions activated by the placebo effect; several regions overlap with areas targeted by brain-stimulation therapy for depression.
These findings have important implications for interpreting placebo-controlled clinical trial results and suggest that the placebo effect could potentially be leveraged as a therapeutic tool.

A network of brain regions activated by the placebo effect overlaps with several regions targeted by brain-stimulation therapy for depression, according to a new analysis by a team that included several researchers from Massachusetts General Hospital (MGH), who collaborated with colleagues at Sunnybrook Health Sciences Centre at the University of Toronto. The findings of this study, published in Molecular Psychiatry, will aid in understanding the neurobiology of placebo effects and could influence how the results of clinical trials of brain stimulation are interpreted. This work may also offer insights on how to harness placebo effects for the treatment of a variety of conditions.

The placebo effect occurs when a patient’s symptoms improve because he or she expects a therapy to help (due to a variety of factors), but not from the specific effects of the treatment itself. Recent research indicates that there is a neurological basis for the placebo effect, with imaging studies identifying a pattern of changes that happen in certain brain regions when a person experiences this phenomenon.

The use of brain-stimulation techniques for patients with depression that doesn’t respond adequately to medication or psychotherapy has gained wider use in recent years. Transcranial magnetic stimulation (TMS) is a non-invasive treatment in which a clinician applies a coil to the patient’s head and delivers electromagnetic pulses to the brain. The effect of TMS on brain activity has been established over the last three decades in animal and human research studies, with several TMS devices approved by the Food and Drug Administration for treating depression. What’s more, there’s growing research on the use of deep brain stimulation (DBS, which requires an implanted device) for hard-to-treat depression, too.

The senior author of the Molecular Psychiatry paper, Emiliano Santarnecchi, PhD, director of the Precision Neuroscience & Neuromodulation Program at the Gordon Center for Medical Imaging at MGH, saw studies of brain stimulation as a unique opportunity to learn more about the neurobiology of the placebo effect. Santarnecchi and his co-investigators conducted a meta-analysis and review of neuroimaging studies involving healthy subjects and patients to create a “map” of brain regions activated by the placebo effect. They also analyzed studies of people treated with TMS and DBS for depression to identify brain regions targeted by the therapies. The team found that several sites in the brain that are activated by the placebo effect overlap with brain regions targeted by TMS and DBS.

Release date: 22 February 2022
Source: Massachusetts General Hospital