Mouse Study: Researchers Devise Non-Invasive Form of Deep Brain Stimulation

Researchers at the Massachusetts Institute of Technology (MIT),  in collaboration with Beth Israel Deaconess Medical Center (BIDMC) and the IT’IS Foundation in Switzerland, have devised a non-invasive form of deep brain stimulation.

This new approach could make deep brain stimulation less risky, less expensive, and more accessible to patients with Parkinson’s disease and other disorders. Rather than requiring surgery to implant electrodes inside the brain, this new method works by applying electrodes to the scalp.

So far, the new approach has been studied in live mice where it was shown to selectively stimulate deep brain structures without affecting the activity of cells in the overlying regions. The findings are published in the journal Cell.

“Traditional deep brain stimulation requires opening the skull and implanting an electrode, which can have complications. Secondly, only a small number of people can do this kind of neurosurgery,” says senior author Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT.

Traditional deep brain stimulation has been used successfully on many patients with Parkinson’s disease. It has also been used to treat some patients with obsessive compulsive disorder, epilepsy, and depression, and is currently being explored as a treatment for autism. The new, noninvasive approach could make it easier to adapt deep brain stimulation to treat additional disorders, the researchers say.

“With the ability to stimulate brain structures non-invasively, we hope that we may help discover new targets for treating brain disorders,” says the paper’s lead author, Nir Grossman, a former Wellcome Trust-MIT postdoc working at MIT and BIDMC, who is now a research fellow at Imperial College London.

When treating Parkinson’s disease, electrodes are typically placed in the subthalamic nucleus, a lens-shaped structure located below the thalamus, deep within the brain. Electrical impulses delivered to this region of the brain have been shown to improve many symptoms of the disease, but the surgery needed to implant the electrodes carries risks, including brain hemorrhage and infection.

Other researchers have tried to noninvasively stimulate the brain using techniques such as transcranial magnetic stimulation (TMS), which is FDA-approved for treating depression. Since TMS is noninvasive, it has also been used in normal human subjects to study the basic science of cognition, emotion, sensation, and movement.

However, using TMS to stimulate deep brain structures can also result in surface regions being strongly stimulated, resulting in modulation of multiple brain networks.

The MIT researchers figured out how to deliver electrical stimulation deep within the brain, via electrodes placed on the scalp, by taking advantage of a phenomenon known as temporal interference.

This strategy requires generating two high-frequency electrical currents using electrodes placed outside the brain. These fields are too fast to drive neurons. However, these currents interfere with one another in such a way that where they intersect, deep in the brain, a small region of low-frequency current is generated inside neurons. This low-frequency current can be used to drive neurons’ electrical activity, while the high-frequency current passes through surrounding tissue with no effect.

By tuning the frequency of these currents and changing the number and location of the electrodes, the researchers can control the size and location of the brain tissue that receives the low-frequency stimulation. They can target locations deep within the brain without affecting any of the surrounding brain structures. They can also steer the location of stimulation, without moving the electrodes, by altering the currents. In this way, deep targets could be stimulated, both for therapeutic use and basic science investigations.

“You can go for deep targets and spare the overlying neurons, although the spatial resolution is not yet as good as that of deep brain stimulation,” says Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research.

Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory, and researchers in her lab tested this technique in mice and found that they could stimulate small regions deep within the brain, including the hippocampus. They were also able to shift the site of stimulation, allowing them to activate different parts of the motor cortex and prompt the mice to move their limbs, ears, or whiskers.

“We showed that we can very precisely target a brain region to elicit not just neuronal activation but behavioral responses,” says Tsai. “I think it’s very exciting because Parkinson’s disease and other movement disorders seem to originate from a very particular region of the brain, and if you can target that, you have the potential to reverse it.”

Significantly, the new approach did not activate the neurons in the cortex, the region lying between the electrodes on the skull and the target deep inside the brain. The researchers also found no harmful effects in any part of the brain.

Source: Massachusetts Institute of Technology