Many people with drug-resistant depression have found relief via transcranial magnetic stimulation (TMS). Yet the mechanism of this relief has been unknown. Now a study finds that TMS may work by correcting connectivity.

Researchers at Weill Cornell Medical College used functional MRI to scan the brains of 17 patients with depression and 35 healthy volunteers while they were not focusing on anything in particular. Previous research has shown that the regions active in this resting state, known as the default mode network, are hyperconnected in depression. Because these areas regulate internal focus, scientists believe the extra connectivity may be related to depression's repetitive ruminations.

The new study first confirmed these regions' hyperconnectivity in the people with depression. Then the patients received a standard five-week course of TMS before their brains were scanned again. Not all patients benefited, but those who did revealed a pattern. Patients who improved no longer had too many connections; their scans were indistinguishable from those of healthy subjects. In addition, patients who initially had tighter links between resting-state regions were more likely to respond to TMS—further evidence that this finding explains how TMS treats depression.

The results suggest a way to eventually customize treatment. A patient could undergo a quick fMRI scan, for example, to learn whether his or her brain is hyperconnected—and if not, avoid a costly and time-consuming regimen of TMS. Study co-author Marc Dubin, a physician and neuroscientist at Weill Cornell, notes that targeting a person's specific abnormalities could help individuals find an effective treatment more quickly.