Stimulating Brain Function, One Pulse at a Time

Someday, treating children with disabling neurological conditions could be as simple as stimulating the brain with a magnetic pulse. The technology, Transcranial Magnetic Stimulation (TMS), may help accelerate recovery from strokes and improve our understanding of Tourette syndrome, ADHD, neurofibromatosis , and other disorders.

TMS isn’t new technology. The first handheld version was developed in the 1980s in Britain. A TMS device is FDA-cleared for treating medication-resistant depression in adults.

However, Cincinnati Children’s is among the few medical centers nationwide studying how these devices can stimulate a child’s brain – initially for research and potentially as a tool for therapy.

“We are studying one of the most basic processes that the brain needs to learn – the process of brain cells making stronger connections,” says Donald Gilbert, MD, MS, who established the TMS lab at Cincinnati Children’s in 2001. “With this technology, we can measure that process. Not only that, we can modulate that process.”

A Visit to the TMS Lab

The TMS lab occupies an exam-sized room in Cincinnati Children’s clinical neurophysiology unit. The stimulation equipment is mounted on a wheeled cart, about the size of a filing cabinet. The pulse is delivered by a hand-held electromagnetic coil. While the patient sits in an adjustable chair, pediatric neurologist Steve Wu, MD uses a tracking camera to align the coil with an MRI brain image appearing on a nearby computer screen. Once placed, the magnet emits a rapid series of pulses. At full power, the magnet can emit a 2-Tesla pulse, similar in strength to an MRI scan.

In a typical test, the pulse targets the brain region that controls motor function, which causes the patient’s hand to twitch. The intensity of that twitch is measured by sensors attached to the patient’s hand.

“Different patterns of pulses can result in different effects,” Wu says. “One way of setting the device can excite a particular region of the brain. Another way can moderate the response.”

Some patients report a mild tingling sensation in their scalp, but no pain. No serious side effects have occurred at Cincinnati Children’s, Gilbert says.

Taking on Tourette

Researchers are exploring multiple ways to use the stimulation technology. In recent studies involving adults, Wu and Gilbert have demonstrated that people with Tourette syndrome do not respond as strongly to the stimulation as those without the condition. Wu presented these findings in June 2009 at the 5th International Scientific and Clinical Symposium on Tourette Syndrome in New York, and in April 2010 at a scientific platform at the American Academy of Neurology annual meeting in Toronto.

“The conclusion we draw is that there is a significant difference in the neuroplasticity of the brain (of a person with Tourette’s),” “We can directly measure this difference, which might allow us to find ways to identify children sooner and intervene early to prevent
bad outcomes”, Wu says.

Overall, Tourette syndrome occurs in about 3 per 1,000 births, with most people diagnosed as children. About 90 percent largely outgrow their tics by adulthood, but clinicians cannot predict which children will have Tourette’s as adults, Gilbert says.

Several medications are used to treat Tourette’s, but none completely control unwanted movements. Some tics also are treated with Botox injections, while some severe cases receive deep brain stimulation, a non-FDA approved surgical treatment that involves inserting
wires at key focal points in the brain.

Early studies have shown mixed results when attempting to use TMS as a therapy. "However, newer equipment and recently developed techniques offer more potential", Wu says. Cincinnati Children’s plans to further evaluate that potential with a small clinical trial beginning later this year.

Stimulating Speech

TMS technology also may offer a way to accelerate post-stroke recovery. Jennifer Vannest, PhD, a neurology researcher at Cincinnati Children’s and Jerzy Szaflarski, MD, PhD, at the University of Cincinnati Medical Center designed a study involving adult stroke patients with an inability to speak normally.

After a stroke, the brain attempts to re-wire itself to move functions that had been located in the damaged area to other parts of the brain. In this study, researchers use functional MRI (fMRI) scans to locate the new focal areas controlling speech, then use the TMS device to stimulate those areas.

“We’re pulsing their brains in the exact areas that they are using to try to talk, to see if we can help improve their function,” Gilbert says.

Next Steps

An increasing number of sites in the United States are conducting research or providing therapy using TMS devices, including the Lindner Center of Hope and the Drake Center, both in Greater Cincinnati. Gilbert and Wu say that’s just the beginning.

In addition to their work in Tourette’s and stroke, the TMS lab is working on two NIH-funded studies involving children with ADHD. The lab also has begun recruiting participants for a study conducted by Cincinnati Children’s researchers Elana Harris, MD, PhD, in Psychiatry and Mark DiFrancesco, PhD, in Radiology. They seek to determine whether TMS can help reduce anxiety among teens with obsessive compulsive disorder (OCD).

“About 70 percent of children with tic disorders also have symptoms of OCD,” Harris says.

That supports the belief that similar types of brain circuitry disruptions are causing tics for some children and compulsive behaviors in others. The ultimate goal is to determine whether TMS pulses can affect the circuitry involved in compulsive behaviors. Functional magnetic resonance images (fMRI) are obtained before and after a single 30-minute TMS session in each subject to determine whether TMS can de-activate areas of the brain that are overactive in patients with OCD.