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Scientists understanding, altering brain’s circuitry

CHICAGO – Every day during a four-year deep depression, Sean Miller thought of ending his life. Nothing relieved the emotional darkness – not therapy, not medication, not loving attention from family and friends.

Then doctors in Toronto implanted electrodes in his brain and switched on an electrical current, and everything changed. Within a month, hope began to flicker. Within six months, Miller felt normal again. “It’s a miracle,” said Miller, 41.

Actually, the credit goes to scientists’ growing understanding of the electrical architecture of the brain – a vast, complex network of circuits that record and relay information – and a technique that offers new hope to people with treatment-resistant illnesses.

Deep brain stimulation, the treatment Miller received, employs electricity to jolt the brain in pinpointed locations. Already in use to treat Parkinson’s disease, the therapy is being tested for patients with severe depression, chronic pain, epilepsy, obsessive compulsive disorder, traumatic brain injuries and Alzheimer’s disease.

“I believe this field is where heart pacemaker devices were 25 to 30 years ago. Brain pacemakers are going to have a significant impact on the treatment for a number of neurological and behavioral conditions,” said Dr. Ali Rezai, director of Cleveland Clinic’s Center for Neurological Restoration.

Whether that promise will pan out is far from certain. Most research studies under way are in their early stages. And scientists readily acknowledge they don’t really know yet what works, under what conditions and for what period. “We are going where no man has gone before: inside areas of the brain that have previously been uncharted,” said Dr. Andres Lozano, a professor of neurosurgery at the University of Toronto.

‘The brain is an electrical organ’

The buzz surrounding the procedure is a sign that science’s growing knowledge of the brain’s circuitry is generating exciting avenues for medical treatments. Doctors who now have to fight stubborn diseases primarily by dosing the brain with chemicals have hope of intervening more directly and precisely.

Guiding researchers’ efforts are new brain maps generated by sophisticated imaging technologies such as functional MRIs and PET scans.

By recording activity in both sick and healthy people, scientists are learning how brain circuits work and discovering where significant breakdowns seem to occur.

Those locations become possible targets for deep brain stimulation, or the application of a constant current of electricity to a specific location in the brain. The current tamps down circuits firing abnormally or revs up circuits that are underactive, experts theorize.

“The brain is an electrical organ, so it makes sense to use electrical stimulation to try to alter its activity,” said Dr. Roy A.E. Bakay, professor of neurological surgery at Rush University Medical Cener in Chicago, which has performed hundreds of the procedures on Parkinson’s patients.

The technique involves drilling two dime-size holes in the skull and guiding electrodes to a spot about the size of a small olive. Then electrodes are connected with leads that snake down under the skin of the neck to a battery-operated device implanted under the collarbone.

At first, Sean Miller felt nothing when doctors turned on his neuro-stimulator after his February 2007 surgery.

“I was devastated,” said Miller, whose four-year depression hadn’t responded to more than 15 medications, electric shock therapy or years of talk therapy. Almost 2 million people with major depression in the U.S. get no relief from conventional treatments.

But one morning almost six months later, after doctors had tinkered repeatedly with the settings for his device, Miller awoke and realized “the pain, the fear and the anxiety were gone.”

So far, the painful feelings haven’t come back, though he still has better and worse days. “I’m so incredibly grateful. I didn’t think I had a chance of ever getting better,” he said.

Preliminary science, potentially lucrative

About 300 medical centers offer deep brain stimulation to patients with Parkinson’s disease in the United States, and about 40,000 procedures have been performed across the world.

But medical device companies such as Medtronic Inc. and St. Jude Medical Inc., which pay for most ongoing research across the U.S., see enormous potential to expand the market.

If the treatment proves effective for other psychiatric and neurological illnesses that don’t respond to conventional therapies, it will be lucrative for hospitals and doctors, as each procedure can cost $150,000.

The science, however, is still at a very preliminary stage. In more than a dozen interviews, scientists said they were still uncertain which patients are most likely to benefit from these procedures, whether relief of symptoms will be long-lasting and what the long-term side effects are likely to be.

Complications from surgery can include brain bleeds or hemorrhages, infections, problems related to medical hardware, post-surgery seizures and headaches, pain and severe mood fluctuations, reports suggest.

Given these risks, deep brain stimulation should be a “last resort for stringently selected patients” who have failed all other therapies, said Dr. Wayne Goodman of the National Institute of Mental Health.

Still, some of the early results are remarkable.

A year ago, researchers in New York and New Jersey reported that a minimally conscious man in a nursing home who appeared unaware of his surroundings began speaking single words and responding to people after electrodes were implanted in his brain.

The procedure may have activated neural circuits that were intact but impaired after an assault disabled the 38-year-old man, said Dr. Nicholas Schiff, a neurologist at Weill Cornell Medical College.

His team has received approval from the Food and Drug Administration to study 11 additional patients with traumatic brain injury.


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