Transcranial magnetic stimulation (TMS) is a transformative method of stimulating and resetting brain circuits to relieve symptoms of depression, as well as other diseases of the mind and brain. UCLA Health practitioners have been at the forefront in adopting TMS therapy and are working to make it even more effective through “precision medicine” innovations.
The U.S. Food and Drug Administration approved TMS in 2008 for treatment-resistant major depressive disorder. It is highly effective, providing substantial benefit to two-thirds of patients even when medications have not been helpful. Patients most commonly receive treatments once a day for six to nine weeks and can feel relief from their depression within a few weeks. In the years since, TMS also has been shown to be effective for people with obsessive compulsive disorder, addiction, chronic pain, and tinnitus.
For the treatment of depression, TMS therapy uses magnetic fields to stimulate the prefrontal cortex. Most patients have experienced improvements with a course of therapy, but the rate and extent of success varies. UCLA Health researchers have created new “precision TMS” approaches that can help each individual patient recover more rapidly and completely from their depression.
UCLA Health has invented a novel treatment method called 5x5 (“five-by-five”), which involves patients receiving five TMS treatments per day for five days, with relief coming within days.
“TMS is a highly effective treatment for depression, but the burden of coming to treatment daily for six to nine weeks is too great for many patients,” said Andrew Leuchter, MD, Distinguished Professor of Psychiatry and director of the TMS Clinical and Research Service. “Our 5x5 protocol appears to be at least as effective as the longer course of treatment and provides much more rapid relief. Our goal is to have more than 85% of patients fully recover from depression with TMS.” The 5x5 treatment approach has not yet been reviewed by the FDA, so is considered off-label treatment.
Key to the success is UCLA’s “precision TMS” treatment approach. An expert psychiatrist sees the patient at each treatment session, and an MRI scan of the brain is used to “neuronavigate” to a personalized target for each individual. UCLA Health also is one of a handful of programs across the nation to use robotics to target the stimulation site enabling greater precision in treatment. This technology is not available through any other provider in Southern California.
“The Axilum Cobot defines the next generation of care for depression,” said Dr. Leuchter. “The Cobot uses the MRI image to place the coil on the head with millimeter accuracy for every treatment. If the patient moves their head during treatment, the Cobot actually moves with them.”
Pupil constriction amplitude linked to symptom improvement
Another precision TMS approach examines pupillometry, the eye’s response to light. In two recent studies, UCLA Health scientists found that the pupil’s response to light before TMS treatment correlated with improvements in depression symptoms over the course of therapy. Pupil size reflects activation of the autonomic nervous system, which controls involuntary functions and is negatively affected in people with depression.
The first study, appearing in the Journal of Affective Disorders, reported on outcomes for 51 patients who underwent daily TMS sessions. Before receiving treatment, researchers measured the patients' baseline pupillary constriction amplitude (CA): how much the pupil shrinks when exposed to bright light. The pupil’s constriction is an indicator of parasympathetic nervous system function. The researchers found a significant association between baseline pupil constriction amplitude and symptom improvement, indicating that a greater CA at baseline was associated with a better outcome.
The second study, published in Brain Stimulation, compared patients who were treated for depression with one of two common TMS protocols: 10 Hz stimulation and intermittent theta burst stimulation (iTBS). With 10 Hz stimulation, magnetic pulses are delivered at a fixed rate of 10 pulses per second, a continuous and relatively high-frequency stimulation; iTBS is a faster form of stimulation with bursts of three pulses at 50 Hz, repeated with short breaks between bursts. This pattern is thought to mimic the natural rhythm of certain brain activities.
The researchers found that people with slower pupillary constriction had significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10 Hz treatment.
“These results suggest we may be able to use a simple test of the pupil to identify who is most likely to respond to electromagnetic stimulation of the brain to treat their depression,” said researcher Cole Citrenbaum, lead author of both studies and a researcher with the TMS Clinical and Research Program at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
Measuring pupillary reactivity before starting a round of TMS could help practitioners more precisely tailor the frequency of brain stimulation to each patient, resulting in better outcomes, Citrenbaum said.
“As we better understand the complex brain activity underlying depression, we move closer to matching patients with the treatments that ensure their full recovery,” Dr. Leuchter said.
TMS for chronic concussion symptoms
UCLA Health researchers also are testing the benefits of personalized brain stimulation to reset a potentially over-sensitized brain circuit in people with long-term symptoms following a concussion.
Kevin Bickart, MD, PhD, an assistant professor of neurology at UCLA’s David Geffen School of Medicine and the UCLA Steve Tisch BrainSPORT Program, said the maladaptation of the circuit may prevent the brain from letting go of fears about returning to pre-injury levels of activity and resolving symptoms. This, in turn, leads people to avoid certain everyday activities because they may trigger headaches, dizziness, sensitivity to light, brain fog and depression or anxiety.
Researchers are using TMS to disrupt that oversensitive, overactive circuit, to diminish those fears and enhance coping ability, he said. “We get an MRI on everyone at baseline to map their whole brain and find that one circuit,” Dr. Bickart said.
Avoiding exercise, using a computer, or going outside into bright sunlight can be protective in the short run, he said, but, in the long term can cause intolerance, sensitivities and deconditioning, and ultimately worsen symptoms for some people.
“It is important as a public health concern to lessen the burden and cost of chronic concussion symptoms,” said Dr. Bickart, principal investigator of the four-year study, which received a $3 million grant from the Department of Defense. “It’s been hard to even diagnose, let alone find targets for treatment of this condition.”
The treatment could potentially help the 30% to 50% of people who still have debilitating symptoms more than three months after a concussion, despite no observable injury on a brain scan, he said.
