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The Promise of Transcranial Magnetic Stimulation

Roy Hamilton, associate professor of Neurology and Physical Medicine and Rehabilitation, standing in the Brain Science, Innovation, Translation, and Modulation Center

Recently, actor Bruce Willis announced that he would step away from his acting career, due to complications resulting from aphasia.

Aphasia is the loss or impairment of the ability to speak or write, and it can result from damage in the area of the brain that controls language expression and comprehension. Damage can be a result of stroke, head injury, brain tumor, infection, or dementia.

For now, the only treatment for aphasia is speech and language therapy, which helps patients learn other ways to communicate. However, research led by Penn Medicine shows that transcranial magnetic stimulation (TMS) might help stimulate brain repair by helping the brain “reorganize” signals around the damaged area.

TMS is a non-invasive technique that excites neurons in the brain via magnetic pulses passed through the scalp from coils of wires. It has been approved by the FDA to treat major depression since 2008, and pain associated with certain migraine headaches since 2013. In 2020, Penn launched the Brain Science, Innovation, Translation, and Modulation (brainSTIM) Center, which brings together a team of leading neuroscientists, neurologists, psychiatrists, psychologists, and engineers at Penn using neuromodulation techniques to research, repair, and enhance human brain function — the first multidisciplinary translational center of its kind in the region.

Currently, TMS is only approved to treat a limited number of conditions. While not yet available to patients, researchers at Penn Medicine are hopeful that their ongoing studies will illustrate broader applications for this innovative, noninvasive treatment method, and emphasize the importance of continued funding for further research.

“Imaging reveals that people tend to rely on the left side of their brain for language, but patients with aphasia actually use both. This tells us that brain functions are a lot more flexible than we previously thought,” said Roy Hamilton, MD, MS, an associate professor of Neurology and Physical Medicine and Rehabilitation, and director of the brainSTIM Center in the Perelman School of Medicine at the University of Pennsylvania. “Our research, which is currently under a phase II clinical trial, shows promising evidence that when we use TMS to target the damaged areas of a patient’s brain that is causing aphasia, the brain is able to recruit different, healthy parts of itself, and create new pathways, bypassing the injured area,” he explained.

Existing research on TMS as a treatment for aphasia has been produced by promising, but small proof-of-concept studies. Hamilton says that in order to be widely adopted for treatment of aphasia, TMS would have to be employed successfully in substantially larger clinical trials, and suggests that while it’s hard to predict how long this will take, it could be several years, underscoring the importance of continued support and funding for research.

The brainSTIM Center also investigates the factors that predict who will react from TMS, and what areas to target.

“Each person’s brain reorganizes differently after a stroke or other injury,” said Hamilton. “Part of our research in the brainSTIM Center is an attempt to gain a fundamental understanding of how stimulation affects the brain, and what underlying properties make it more likely that one part of the brain will take on the function of the damaged area of the brain.”

Hamilton hopes to develop biomarkers — including genetic factors — that can show how plastic, or adaptable to outside stimuli, an individual’s brain is, which may determine how responsive they will be to brain stimulation. That is, some people need more or less stimulation, and this may influence whose brains are more likely to recover the ability to communicate. Identifying biomarkers, or other benchmarks that clinicians could test for would allow providers to determine which patients would benefit from TMS to treat their aphasia, and which may not, allowing doctors tailor treatment to individual needs.

For example, Hamilton is interested in the biomarkers that may inform clinicians about how flexible an individual’s brain is. His lab is currently researching whether a patient’s levels of a protein known as brain-derived neurotrophic factor (BDNF), which is known to be important for brain plasticity, can predict whether or not language can be recovered in patients living with post-stroke aphasia.

“Our brain naturally attempts to repair itself after it’s been injured. We are hoping to be able to use TMS to guide the brain’s reorganization and repair, and optimize stimulation in each individual, hopefully resulting in better outcomes for patients experiencing aphasia or other cognitive difficulties,” Hamilton added.

Magnetic stimulation also shows promising signs of being able to help other health problems, Hamilton added. For example, new research produced in collaboration with Penn Medicine’s department of Cardiology revealed that magnetic stimulation of a nerve cluster in the neck in patients with dangerous arrhythmias and reduce the rate of ventricular tachycardia (VT) storm in the hospital.

“We’ve just scratched the surface of applications of magnetic stimulation,” said Hamilton. “I’m eager to continue to expand our understanding of how stimulation impacts the brain and nervous system, and how we can use that research to develop therapies that help patients who previously had no other options.”

While targeted and noninvasive, there are still some risks associated with TMS. There is a very small chance of inducing a seizure, Hamilton noted, adding that it is extremely uncommon, particularly using widely adopted stimulation guidelines.

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Views expressed are those of the author or other attributed individual and do not necessarily represent the official opinion of the related Department(s), University of Pennsylvania Health System (Penn Medicine), or the University of Pennsylvania, unless explicitly stated with the authority to do so.

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