UCLA Researchers Find Magnetic Waves Increase Chemical GABA in the Brain, to Treat Depression

The brain is both an electrical and chemical organ.

That’s something that often gets overlooked, according to UCLA’s Dr. Andrew Leuchter, Director of the Transcranial Magnetic Stimulation (TMS) Clinical and Research Program. Psychiatrist Dr. Leuchter is an expert in the use of TMS for treatment resistant depression.

We are used to thinking of talk therapy, or medications as the only options to address mental health. But today cutting-edge researchers like Leuchter are looking at depression as a problem with the brain’s network wiring.

Depression has emerged as the most debilitating condition in the world for the first time surpassing cancer, heart disease, and AIDS according to the World Health Organization. And according to Leuchter, we need a new treatment.

Although a variety of antidepressant medications are available, today nearly two-thirds of patients do not benefit from initial pharmacotherapy and remain symptomatic and functionally impaired.

Recent studies show that if people stick with medications, and stick with them long enough to try various different combinations results can be favorable. But according to Leuchter:

“It can take 12 to 18 months to try enough medications and combinations.”

For people with major depressive disorder, spending months trying different medications or combinations can be challenging. What’s exciting about TMS technology says Leuchter is that it holds potential as a first line treatment, with few side effects.

How It Works

Transcranial Magnetic Stimulation (TMS) involves placing an electro magnetic stimulator on a patient’s scalp. The stimulator sends a series of magnetic pulses into the brain.

The key to the treatment, according to Dr. Leuchter is that TMS kicks off a “reset” program, that makes both biochemical and connectivity changes across the brain.

“Our work suggests that if we are stimulating one area of the brain, this effects how that area relates to other areas of the brain,” says Leuchter. “The signals we are putting into the area, are spreading to related areas and mood regulating circuits. It’s the relationship among those areas that is changed.”

“TMS interacts with deeper areas and other circuits on the surface of the brain in the Fronto-parietal circuit.” According to Leuchter this Fronto-parietal circuit (located right behind and above the ear in the parietal lobe), appears to play a role in mood regulation. 

TMS delivers a one-two punch to promote brain health, in both an electric and chemical way.

The brain is electrical and regulates neuronal activity and plasticity by increasing voltage-dependent calcium channels. A neuron needs an electric signal to activate.

At the cellular level, TMS delivers the electricity to increase the calcium ions channels in a cell, and this in turn stimulates an increase in neurotransmitters. But only approved by the FDA since 2008, the mechanisms of how TMS actually work haven’t been well understood – until now.

A recent study from Dr. Leuchter’s lab shows increased levels of GABA from TMS treatments.

GABA (y-aminobutyric acid) is the most widespread neurotransmitter in the brain, and like all neurotransmitters, helps to carry signals across a synapse.

GABA is the chief inhibitory neurotransmitter, which means that it weakens or slows down signals. Its principle role is reducing neuronal excitability, and the latest research suggests that it plays a key role in depression.

In the journal Biological Psychiatry, Penn State University biologist Bernhard Lűscher reports that depression may arise from a deficit in GABA, throwing GABA and glutamate out of balance. In an attempt to compensate, the body increases production of glutamate. At first, the glutamate surge leads to lots of neuron excitation. But eventually the receptors for glutamate retreat, preventing brain cells from firing. This deficit in GABA according to Lűscher causes feelings of numbness and disengagement from the world.

Dr. Leuchter says his work also seems to correlate well with recent findings on using Ketamine experimentally to treat depression. (Ketamine appears to help patients with major depression by restoring balance to the GABA-glutamate system.)

As an expert on the front lines of TMS, Leuchter’s study comes at a time when the field of psychiatry is looking for new evidence-based solutions.

A New Yorker article “The Troubled History of Psychiatry” (May 27, 2019) challenges the legitimacy of the profession, citing that treatment often depends on the caliber of the therapist. Harvard Professor Anne Harrington argues that traditional medicine and disease treatment relies on scientific experiment, accurate diagnosis and targeted therapies. But that the field of psychiatry has failed to show efficacy and clinical trial results on how patients can get better with talk therapy and medication in the least amount of time.

In an effort to make psychiatric treatment more evidence-based, TMS could provide patients with needed options. Dr. Leuchter is seeing potentially promising results in the over 6,000 patients that have undergone treatments at UCLA.

TMS: Different Than a TENS Unit

This isn’t the first time electrical impulses are used to treat pain in the body. What people are more familiar with is a small TENS unit, used in physical therapy offices to treat back pain.

TENS units deliver small electrical impulses through electrodes that have adhesive pads to attach them to a person’s skin. These electrical impulses flood the nervous system, reducing its ability to transmit pain signals to the spinal cord and brain. The electrical impulses cause the body to produce natural pain relievers called endorphins.

“On the one hand TMS is very different but on the other hand not at all,” explains Dr. Leuchter.  “A TENS unit puts out electricity. TMS puts out magnetic energy.”

“TENS is generated by a 9 volt battery very weak signal, or a AAA battery tiny electrical micro currents. We’re [with TMS] using magnetic pulses strong enough to make a nerve cells activate and fire.”

Leuchter sees both a small TENS unit and TMS as forms of neuromodulation. But TMS delivers a stronger magnetic pulse, which produces electrical stimuli once it penetrates the cranium, and in turn influences how the nerve cells fire.

What’s Next: Machine Learning

“We’re using machine learning EDT caps on the patients’s head and we record their brain activity and we can see how pulses got through the brain networks,” says Leuchter.

The hope is that TMS will someday be easy to personalize to each patient’s brain. And developing briefer and more rapid forms of treatment will also be critical. So for example according to Leuchter instead of 45 minutes, a TMS treatment session could take 3 minutes.

Leuchter also hopes that insurance companies will soon cover TMS as a first line of treatment. Currently in most states, patients have to fail with 3 or so different medications before health insurance will pay for TMS visits.

For now the aim is to make the treatments as efficient as possible by finding the resonant frequency that works best for each patient in less time. And to make TMS more available, especially for patients with depression that has failed to respond to medications. Dr. Leuchter says UCLA will be opening a new community clinic offering TMS, in Pasadena sometime in early 2020.