Researchers in the US have uncovered how a fast-acting form of brain stimulation may relieve depression symptoms in mice by restoring damaged brain connections caused by chronic stress.

Transcranial magnetic stimulation (TMS) is a non-invasive therapy approved to treat depression, particularly in people who do not respond to medication. It works by delivering brief magnetic pulses to stimulate specific brain regions. A newer version of the treatment, called accelerated intermittent theta burst stimulation (aiTBS), can reduce symptoms within days instead of the several weeks required for standard TMS. However, scientists still do not fully understand how the treatment affects brain cells and circuits.

A team at the University of California Los Angeles (UCLA) developed a small cooled magnetic coil that was positioned above the mice’s heads and delivered the focused magnetic pulses while the mice were awake and moving freely, closely mimicking how patients receive aiTBS in the clinic.

After just one day of aiTBS in mice exposed to chronic stress, the loss of dendritic spines — tiny structures that help brain cells communicate — was reversed. This happened in a specific group of brain cells involved in communication between brain regions, called intratelencephalic (IT) neurons. The treatment also improved stress-related behaviours for at least one week after stimulation.

When the researchers blocked the activity of IT neurons during aiTBS, using a specific drug that temporarily switches off specific brain cells, the antidepressant effects disappeared.

"By studying these treatments in mice, we can systematically test how different stimulation parameters reshape brain circuits, which may ultimately help us tailor neuromodulation therapies to individual patients," said Scott Wilke, from UCLA, co-leader of the study published in Cell.