School of Medicine

Why doesn’t deep-brain stimulation work for everyone?

Brain networks corresponding to functions such as vision (blue) and attention (green) mingle and share information in structures deep inside the brain, as seen, for example, in the bottom right corner of this color-coded composite MRI image. Researchers at Washington University School of Medicine in St. Louis have mapped nine functional networks in the deep-brain structures of 10 healthy people, an accomplishment that could lead to improvements in deep-brain stimulation therapy for severe cases of Parkinson’s disease and other neurological conditions. (Image: Scott Marek)

People with severe Parkinson’s disease or other neurological conditions that cause intractable symptoms such as uncontrollable shaking, muscle spasms, seizures, obsessive thoughts and compulsive behaviors are sometimes treated with electric stimulators placed inside the brain. Such stimulators are designed to interrupt aberrant signaling that causes the debilitating symptoms. The therapy, deep-brain stimulation, can provide relief to some people. But in others, it can cause side effects such as memory lapses, mood changes or loss of coordination, without much improvement of symptoms.

Now, a study from researchers at Washington University School of Medicine in St. Louis may help explain why the effects of deep-brain stimulation can vary so much – and points the way toward improving the treatment. The stimulators typically are implanted in structures known as the thalamus and the basal ganglia that are near the center of the brain. These structures, the researchers found, serve as hubs where the neurological networks that control movement, vision and other brain functions cross paths and exchange information. Each person’s functional networks are positioned a bit differently, though, so electrodes placed in the same anatomical spot may influence different networks in different people – alleviating symptoms in one but not in another, the researchers said.

The findings are published Dec. 10 in Neuron.

“The sites we target for deep-brain stimulation were discovered serendipitously,” said co-author Scott Norris, MD, an assistant professor of neurology and of radiology who treats patients with movement disorders. “Someone had a stroke or an injury in a specific part of the brain, and suddenly their tremor, for example, got better, and so neurologists concluded that targeting that area might treat tremor. We’ve never really had a way to personalize treatment or to figure out if there are better sites that would be effective for more people and have fewer side effects.”

What neurosurgeons lacked were individualized maps of brain functions in the thalamus and basal ganglia. These structures connect distant parts of the brain and have been linked to neurological and psychiatric conditions such as Parkinson’s disease, Tourette’s syndrome and obsessive-compulsive disorder. But their location deep inside the brain means that mapping is technically challenging and requires enormous amounts of data.

Nico Dosenbach, MD, PhD, an assistant professor of neurology and the study’s senior author – along with co-first authors Deanna Greene, assistant professor of psychiatry and of radiology, and Scott Marek, PhD, a postdoctoral researcher, and other colleagues – set out to create individual maps of the functional networks in the basal ganglia and thalamus. Such maps, they reasoned, might provide clues to why people with neurological and psychiatric conditions exhibit such a wide range of symptoms, and why electrodes placed in those structures produce variable results.

“Deep-brain stimulation is a very invasive treatment that is only done for difficult, severe cases,” said Greene, who specializes in Tourette’s syndrome. “So it is difficult to grapple with the fact that such an invasive treatment may only help half the people half the time.”

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