Stimulating the Deep Brain—From the Outside In

Source from Northwestern Medicine

The idea of using electricity to influence the brain isn’t new—it actually dates back to ancient times. In the Roman Empire, a physician named Scribonius Largus used the electricity produced by the torpedo fish to treat ailments like headaches. Over time, other doctors and researchers continued experimenting with electric fish to try to cure a range of conditions. While these early methods occasionally worked, they also came with serious risks, such as skin burns. That’s because the electrical signals from the fish were uncontrolled—especially in terms of strength and duration.

Thankfully, technology has come a long way since then. Today, scientists can use machines to deliver precisely controlled electrical currents to the brain. But how is it possible that electricity can influence brain activity in the first place?

The answer lies in how the brain naturally works. The brain communicates using electrical signals called action potentials. These are like binary signals—comparable to the 0s and 1s used in computers. When a brain cell, or neuron, receives input from other cells, this input basically casts a vote for whether the neuron should send out its own electrical signal. If enough input pushes votes to send a signal, the neuron fires an action potential to send information to other connected neurons. This fast electrical communication system underlies everything the brain does.

By applying weak electrical currents to the brain, we can subtly influence this process—making neurons more or less likely to fire. With stronger currents, we can even trigger neurons to fire directly. This is the principle behind brain stimulation.

Modern electrical brain stimulation techniques fall into two main categories: invasive and non-invasive.

• Invasive brain stimulation involves surgically implanting electrodes into specific areas of the brain. This method is used to treat neurological conditions like Parkinson’s disease. However, due to the need for surgery, it’s generally reserved for patients with serious disorders.

• Non-invasive brain stimulation, on the other hand, uses electrodes placed on the surface of the scalp to generate electric fields that influence the brain. This approach doesn’t require surgery, making it more accessible for both patients and healthy individuals. Historically, though, it’s been limited to surface-level brain regions because electric fields weaken with increasing distance. This meant that deeper brain areas were difficult to reach without also affecting the surface.

That changed in 2017, when researchers introduced a new technique called Temporal Interference Stimulation (TIS). TIS uses two sets of electrodes to deliver two different high-frequency electric fields. On their own, these fields don’t affect the brain much. But where they overlap and are equal to each other—in a specific region of the brain—the interaction of these fields can influence neuronal activity. Crucially, this interaction can be steered toward deeper brain regions by adjusting the placement and strength of the original fields, allowing for targeted deep brain stimulation without surgery.

This innovation sparked excitement in both research and clinical communities. TIS opened the door to stimulating deep brain areas in healthy people and showed promise for treating diseases like epilepsy. Some studies have even explored using TIS to target memory-related regions in hopes of enhancing memory.

However, some critics raised an important concern: while TIS might be able to target deep brain areas, the resulting electric field may not be strong enough to meaningfully affect brain activity.

In response to this challenge, researchers from France and Western University collaborated on a new approach published in Bioelectronic Medicine in 2025. Their goal was to amplify the effects of TIS while staying within safety limits. The result was an advanced version of the technique called Multipolar Temporal Interference Stimulation (mTIS).

Instead of using just two interfering fields, mTIS adds more pairs of electric fields, all focused on the same brain region. With each additional pair, the combined electric field in the target area becomes stronger, making it more likely to affect neuronal activity.

While the idea seems simple, precisely aligning multiple electric fields to interact in the right brain region is challenging. To tackle this, the researchers used computer simulations to predict where the fields would interact most effectively. Then, in animal studies using animals like mice, they implanted electrodes directly into the brain to measure the electric fields and verify their predictions.

By combining simulations and real measurements, the researchers showed that mTIS can significantly increase electric field strength in deep brain regions—without needing invasive surgery. This breakthrough could make deep brain stimulation more effective and accessible, opening new possibilities for treating neurological conditions and studying brain function.

In Summary

Temporal Interference Stimulation (TIS) was a technique that made non-invasive deep brain stimulation possible. Now, with mTIS, researchers have found a way to make that stimulation stronger and more targeted—potentially advancing how we understand and treat the brain.

Original Article: Botzanowski, B., Acerbo, E., Lehmann, S., Kearsley S.L. et al.  Focal control of non-invasive deep brain stimulation using multipolar temporal interference. Bioelectron Med 11, 7 (2025). https://doi.org/10.1186/s42234-025-00169-6