A Gentler Way to Jump-Start the Brain

Scientists in Israel are testing a noninvasive method to electrically stimulate neurons deep in the brain.

Deeply affected: Patients with severe depression may find relief with the help of a wired helmet (above). A magnetic field generated by the helmet harmlessly induces electric currents deep in the brain, giving underactive neurons a much-needed jump start.

Electrically shocking the brain is often the only recourse for people suffering from severe, untreatable depression. While standard antidepressants have little effect on these patients, electroconvulsive therapy (ECT) can sometimes jump-start the brain, lifting people out of depression, at least for a while. But ECT can also carry some serious side effects, including seizures and memory loss.
Now researchers are exploring a gentler approach to electrically stimulating the brain. The technique, called transcranial magnetic stimulation (TMS), uses an external magnetic field to create electric currents within the brain. Until recently, researchers experimenting with TMS have only been able to stimulate superficial brain regions. Now a company in Israel called Brainsway has developed a TMS method that reaches deeper into the brain, to stimulate areas associated with depression and other neurological disorders. If successful, the therapy could provide a new alternative for the two-thirds of patients with major depression who fail to respond to antidepressants.
Brainsway's technology builds on traditional TMS methods, which involve placing an electromagnetic coil close to a patient's scalp. An external power source generates an electric current, which flows through the coil, which in turn creates a powerful magnetic field that travels through the skull, into the brain. Once in the brain, these electromagnetic waves generate electric current, stimulating nearby neurons, which then activate related networks, potentially strengthening connections within the brain.
However, a major limitation in TMS research has to do with the very nature of magnetic fields: electromagnetic waves decay rapidly after a short distance. This constraint has largely limited TMS's reach to brain areas one centimeter below the skull. In order to reach deeper regions, researchers would have to increase the intensity of the electric current flowing through the coil, which could induce painful side effects such as seizures and tissue damage.
Instead, Abraham Zangen, one of two inventors of Brainsway's deep TMS approach, and his colleagues designed a new coil configuration that is able to excite neurons at a depth of four centimeters, using the same intensity of current used in standard TMS coils. Instead of a single coil generating a single magnetic field through the brain, Zangen has outfitted a helmet with a number of small coils, each producing a separate magnetic field. As researchers run a standard current through the helmet, the coils, which are connected in a series, produce multiple fields that add up, generating a much stronger magnetic field that goes deeper into the brain before dropping off.
Zangen and his team have tested the helmet on a group of 50 people with severe depression, all of whom showed no improvement after taking antidepressants. During the double-blind clinical trial, half of the patients underwent deep TMS treatment at electrical intensities comparable to standard TMS for five days a week for four weeks, while the other half underwent similar treatments at lower intensities. Each treatment lasted about 20 minutes, during which patients wore the helmet while researchers periodically administered two-second electrical pulses. After the experiment, 50 percent of the patients who received the higher-intensity version reported significant improvements in sleep, appetite, and overall mood, while none of the others did. Most patients in the higher-intensity group also performed better on a standard cognitive test evaluating depression.

"We observed improved mood and optimism," says Zangen. "For example, people who before were just at home doing nothing were able to go back to work."
Brainsway is currently seeking approval in Europe and the United States for deep TMS as a therapeutic tool for depression and other brain-related diseases. Zangen anticipates that the technology will be approved in Europe within the next few months. Before it gains FDA approval, the company will have to test the technology on a much wider population. Zangen's team is now mobilizing clinical trials in a number of medical centers in the United States, including Johns Hopkins University and Harvard Medical School.
Meanwhile, Brainsway is designing different coils to tackle brain regions associated with other conditions, such as post-traumatic stress disorder, autism, and drug addiction. Zangen says that in addition to stimulating underactive areas of the brain such as those associated with depression, deep TMS can be used to inhibit brain regions that may be abnormally overactive, such as during addiction.
"The idea is, you want to reduce some connectivity that was established during addiction, and actually weaken some synapses in the reward system of the brain," says Zangen. "If you use lower-frequency stimulation, you can actually inhibit overactive neurons and reduce connectivity over the long term."
Alvaro Pascual-Leone, director of the Center for Noninvasive Brain Stimulation at the Beth Israel Deaconess Medical Center, says that while deep TMS may have beneficial effects on depression, it may not work for all patients, and researchers will have to find a way to tailor the technology to each individual.
"It's still unclear how to make TMS optimally antidepressant for any one individual," says Pascual-Leone. "Ultimately, you would have to individualize intervention. But this is the only successful attempt in generating a coil that can reach deep in the brain, and that's exciting."