Current treatments that use electrical deep brain stimulation require a surgeon to open the skull and implant electrodes inside the brain.

Now, in a new study using mice, scientists demonstrate a noninvasive approach called temporally interfering stimulation, which uses electrodes placed on the scalp to electrically stimulate regions deep inside the brain. The experimental technique does not require surgical implants and does not disturb surface brain tissue.

In a paper published in the journal Cell, the researchers - including a team from Massachusetts Institute of Technology (MIT) in Cambridge - report how they tested the new temporally interfering (TI) stimulation method on the brains of mice.

Deep brain stimulation (DBS) was originally developed as a treatment to reduce symptoms of Parkinson's disease, which typically include uncontrollable movements, stiffness, tremor, and problems with walking.

In current approaches to DBS, electrical stimulation is delivered through two electrodes that must be surgically implanted inside the brain.

However, because of their invasive nature, such approaches to DBS carry with them the risk of infection, stroke, and bleeding in the brain.

Noninvasive brain stimulation techniques - such as the transcranial magnetic stimulation that is approved for the treatment of depression - are quite effective at stimulating tissue near the surface of the brain.

Unfortunately, they are less effective at stimulating deeper regions in the brain, especially without also disturbing surface regions.

TI stimulation selectively targets deep brain regions

TI stimulation relies on the fact that placing high-frequency electrodes on the scalp results in the frequency from each electrode being too high for the current to stimulate neurons by itself; the cells' biophysical properties only allow them to become excited by low-frequency currents.

However, setting up the high-frequency currents so that their frequencies are slightly different, where they intersect, allows them to generate a small area of low-frequency current that can stimulate neurons.

For example, it is possible to have an electrode sending a 4,000-hertz signal placed on one side of the head, and another sending a 4,001 hertz signal on the other side.

This is precisely what the researchers did: they set up the high-frequency currents in the scalp electrodes so that they met in a particular region deep inside the brains of living mice.

They first tested the method in physical mockups using computer models, and then, on the strength of those results, they carried out tests in the mice.

Using a technique called c-Fos neuron labeling, they confirmed that TI electrical signals only excited brain cells in the target region and did not disturb neurons in the surface tissue that the high-frequency currents passed through.

In their study paper, the authors describe how they used TI stimulation to target the hippocampus and other small regions deep inside the brains of the mice.

They demonstrated how they could control the size and location of the target area deep inside the brain by changing the frequencies of the electrical signals and altering the number and position of the external electrodes.

It was even possible to selectively stimulate parts of the motor cortex and get the mice to move their whiskers, ears, left paws, and right paws, they note.

Technique may offer new ways to treat and study the brain

In 2016, Prof. Li-Huei Tsai, one of the researchers and a professor of neuroscience at MIT, used mice to show that a type of light therapy may offer a noninvasive treatment for Alzheimer's disease.

That technique shines flickering light into the eyes to set up oscillations of a particular frequency in the brain, resulting in reduced neuron levels of amyloid plaques - a known hallmark of Alzheimer's disease.

Prof. Tsai says that she now wants to find out whether TI stimulation might have a similar effect.

The researchers also plan to study the effects of TI stimulation in humans. They see potential for using it not just to treat brain diseases, but also to study them.

They note that TI stimulation may not be able to target brain regions as precisely as DBS, so the invasive technique may still end up being the treatment of choice for Parkinson's disease.

However, they suggest that the noninvasive technique may still benefit patients with other conditions - such as stroke, memory loss, and traumatic brain injury - that do not require the precise resolution of DBS.

"With the ability to stimulate brain structures noninvasively, we hope that we may help discover new targets for treating brain disorders." - First author Dr. Nir Grossman, Imperial College London, United Kingdom