When a researcher asks a volunteer to slide head-first into the open eye of a magnetic resonance imaging (MRI) machine, the expectation is that the device's magnetic field will penetrate the skull to produce a faithful picture of the brain without changing its behavior. A new study suggests, however, that MRI machines do, in fact, manipulate brain activity—and they change the brain in a way that helps treat depression. In other words, MRIs may be unintentional antidepressants.

Hadi Rokni-Yazdi of Tehran University of Medical Sciences in Iran and his colleagues organized 51 volunteers with major depressive disorder into three 17-person groups. Volunteers in the first two groups received one of two kinds of MRI scan. Those in the third group received phony MRI scans: The magnet was never switched on, but a recording of the sound generated by a genuine session was played to convince the volunteers they had been scanned. All the subjects were taking common antidepressants known as selective serotonin reuptake inhibitors (SSRIs) and all had their level of depression assessed by standard scales before and after the procedure.

Two weeks after the scans, volunteers in the first two groups scored between 35 and 40 percent lower on the depression scales than they scored before the scan. The placebo effect may have played a role; when people believe they are receiving a helpful treatment for anything, they often feel better afterward. But volunteers in the pretend MRI group improved less, only by 15 to 19 percent. So, the researchers reasoned, some other factor must explain why volunteers who received phony MRIs showed less improvement. The results are discussed in the November issue of Brain Imaging and Behavior.

One possibility is that the magnetic field created by the MRI machine somehow acts as an antidepressant. Scientists have been investigating the idea that magnets can relieve depression for more than a decade. Most studies have focused on repetitive transcranial magnetic simulation (rTMS), in which an alternating magnetic field induces electric currents in specific regions of the brain, with mixed results. However, a few studies have asked the same questions about MRIs, which create a weaker magnetic field and thus weaker electric currents. Previously, researchers have found that MRIs or devices that generate similarly weak magnetic stimulation improved mood in patients with bipolar disorder—who fluctuate between mania and depression—and helped relieve depression in rats and mice.

But the evidence so far has failed to persuade most scientists, not least because no one has been able to explain exactly how magnetic stimulation alters brain activity in a way that improves depression—although at least one researcher has a few ideas.

About eight years ago, Michael Rohan of Harvard Medical School’s McLean Hospital was running MRI studies of people with depression and noticed that the volunteers emerged from the scans with improved moods. Rohan has been looking into the matter ever since and has recently finished an as-of-yet unpublished study that "looks favorable," he says. He has even created a tabletop device that produces the same electric fields generated by magnetic pulses inside the MRI machine. Because the electric fields generated by an MRI's magnet are too weak to change the behavior of axons—the long tails of neurons that send out signals—Rohan thinks that, instead, the electric fields somehow synchronize signals in a neuron's dendrites, the many branches that receive signals from nearby cells. Out-of-sync electrical activity has been implicated in many brain disorders.

"We're still in the early stages," Rohan stresses. "All of this is exploratory."

As neuroscience blogger Neuroskeptic points out, another possibility is that the results in the new study are a statistical fluke. Almost all the volunteers improved, and those who recovered the most may have wound up in the first two groups by chance. The smaller the number of participants, the more likely this kind of statistical fluke can occur.

Or, perhaps, it was the placebo effect after all. Volunteers in the fake scan group may have improved less overall because some noticed that, despite attempts to hide it, something was a little off or simply did not buy into the idea as much as volunteers who had received real scans, especially if they had prior experience with MRIs—a question the researchers did not ask.

The study is only the first clinical trial to specifically investigate whether MRIs can help people suffering from major depressive disorder, and the intriguing results will likely inspire other researchers to try similar experiments of their own.