Alternative to Deep Brain Stimulation Could Revolutionize Mental Health

Doctors could soon stimulate the deepest reaches of the brain without surgery.

Brain surgery is one of the most delicate, invasive procedures in medicine. When having brain surgery, you like there awake. In some severe psychiatric cases, you may have an electrode inserted into your brain so you can receive deep brain stimulation. We don’t like it when people mess around inside our heads, but sometimes it can be a medical necessity.

Research published Thursday in the journal Cell promises a safer alternative to these otherwise intrusive ways to get in your head: stimulating neurons deep in the brain without any invasive procedures. The procedure, called temporal interference stimulation, is the latest invention of MIT neuroscientist and engineer Edward Boyden.

“Brief stimulation of the brain can actually cause the brain to clean up the amyloid plaques that are a hallmark of Alzheimer’s Disease,” Boyden tells Inverse. He feels that his new technology can help with a number of neurological conditions without many of the hazards inherent to invasive techniques

Even when guided by a skilled surgeon, there’s a big risk with any invasive brain procedure, Dr. Helen Mayberg, a psychiatrist at Emory University, tells Inverse. “There are lots of risk issues with an implant. You can get an infection, there’s a battery, you have to charge it,” she says.

Dr. Mayberg uses deep brain stimulation in her practice, especially for cases of depression that don’t respond to other treatments. “I would like nothing better than to do what I do but outside the head,” she says.

In the rat study, Boyden and his team used temporal interference stimulation to activate the rats’ hippocampus (the part of the brain most strongly associated with memory formation) which was previously too deep within the brain to reach from the surface. The team also used their new technique to target various parts of the rat’s motor cortex, driving it to reflexively twitch its paws and wiggle its ears and nose.

A rat's brain where the hippocampus is being activated by temporal interference stimulation

Nir Grossman, Suhasa B. Kodandaramaiah, and Andrii Rudenko

“Wiggling your finger is easy,” Dr. Mayberg tells Inverse, pointing out that less advanced techniques have done the same thing. But the motor cortex is much more accessible by non-invasive techniques, and temporal interference stimulation seems likely to reach previously-unattained precision.

Temporal interference works by sending two precise electrical signals into the brain from an electrode resting on the scalp. Boyden’s lab went back to verify that these pulses weren’t causing any brain damage along the way. When the two electrical signals collide, they energize whatever neuron happened to be resting at the point of intersection, causing it to activate.

While temporal interference stimulation could effectively penetrate and stimulate deep into the brains of the mice used in this study, calling it “noninvasive deep brain stimulation” is a misnomer. Rather, the new technique is more similar to transcranial magnetic stimulation, which sends magnetic pulses through the brain in repeated treatments over a period of time, whereas deep brain stimulation is a 24/7 therapy.

“I don’t think this goes head to head with [deep brain stimulation] per se,” Boyden tells Inverse, because there would be no long-term implant that constantly provides a signal.

What the three treatments have in common, however, is that they can help advance medicine by providing doctors with a way to directly control the brain’s behavior as it pertains to psychiatric disorders or recovering from injuries like strokes. They would just be used for different things.

In addition to his goal of helping patients fight Alzheimer’s Disease, Boyden explains that his technique could hasten the brain’s natural plasticity, which is its ability to adapt and self-repair after part of it is damaged or removed.

“If someone has a stroke they may learn to walk but using a new part of the brain,” he tells Inverse. “If we can speed that process up, then great.”

Deep brain stimulation requires an electrode be physically inserted into the brain, which is why people are developing alternative treatments.

Wikimedia Commons / Allurimd

On the other hand, deep brain stimulation is more commonly used for ongoing psychiatric disorders that require constant attention.

“It’s not gonna be replacing [deep brain stimulation] any time soon,” Dr. Mayberg tells Inverse. She thinks that this new research is exciting and promising, but still far away from clinical application, especially one that would be relevant to her practice. In part this is because Boyden has thus far relied on animal models, which often fail to translate to human studies.

But also, her patients require the constant intervention that only an electrode implanted into the brain can provide. She explains that patients with Manic Depressive Disorder who use deep brain stimulation will relapse almost immediately if their electrode is turned off or runs out of batteries, even after years of treatment.

“I’ve got patients who have been implanted ten years, and they’ve been well. They don’t relapse,” Dr. Mayberg tells Inverse. “But if you turn the device off or it breaks, it isn’t like you just walk away and it turns out you didn’t need it.”

Since completing his rat studies, Boyden has begun some human trials at his MIT lab. Because they’re still in-progress, he couldn’t give a statement on how they’re going. But he did say that because the human brain is bigger, more complex, and shielded by a thicker skull, some parameters of his technique will have to be modified from those used in the research published today.

While she probably won’t use it to treat her patients, Dr. Mayberg is excited by temporal interference stimulation’s potential as a diagnostic tool. By targeting different parts of the brain with Boyden’s new technology and seeing how her patients respond, Dr. Mayberg feels that she could have a better idea of where to place the implant so it can do the most good.

“I’m not gonna put two electrodes in one person any time soon,” she tells Inverse. “This is just stage one. In principle, this is the start of something exciting and we’ll see where it goes.”

Abstract: We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.
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