Happiness is a Warm Electrode

Mood Swings in an MRI

The day after her surgery, with her scalp sewn up but the wires still sticking out, Hire is moved to the Cleveland Clinic's main imaging center, where she's wheeled into a tightly packed room containing a functional magnetic-resonance-imaging (fMRI) machine. The device generates powerful magnetic fields to measure the metabolic activity in different areas of the brain in real time. It's shaped like a giant, nine-foot-wide doughnut and has a narrow bed inserted through the center hole. The imaging technician, John Cowan, helps Hire position her head inside the opening and outfits her with earphones and a microphone, while neurophysiologist Kenneth Baker squeezes behind the machine to attach the wires from her head to an external stimulator in another room.

From an adjacent room, Cowan, Malone and Baker watch Hire through a window and on a small video screen, talking to her frequently to keep her calm. For the next 48 minutes, while she tries to remain relaxed and perfectly still, Baker turns the voltage on and off as the machine scans her brain. For 30 seconds, she's happy. Then Baker shuts off the electrodes, Hire's smile fades, and the machine maps how her brain reacts. Another 30 seconds pass, and the happiness returns. Cowan later marvels at the effect of the stimulation on Hire and the other depression patients. "They're always laughing, and I'm wondering, how can you be laughing like this so soon after surgery?"

Regardless of how or even whether DBS is curing Hire's depression, the fMRI scans show that physiological changes in her brain accompany the emotional changes. The scientists can watch different brain areas-which they refer to as "nodes" or "hubs" in a larger circuit-become active, one after the other, in a repetitive pattern. "We're putting electrical impulses into a hub that connects large parts of the brain involved in your mood, your anxiety and your energy level," Rezai says. The more that scientists understand about how the diseased brain functions, he explains, the more they will know how to find the faulty wiring or circuits responsible for it, and from there they can design the therapies to fix it.

Keep on Smiling

The results of these limited tests of DBS are impressive so far. In 2005 the Toronto group found that four out of six patients showed significant improvements. Earlier this year, psychiatrist Thomas Schlaepfer's group at the University of Bonn in Germany announced that all three of his patients were benefiting from the surgery. And the Cleveland-Brown collaboration reports improvements in 70 percent of their patients, half of whom are in complete remission.

Medtronic, a company in Minneapolis that manufacturers the hardware for DBS, is working with the Food and Drug Administration to plan the largest study yet of depression and DBS-a 100-patient trial in which the scientists may delay stimulation in half the patients for six months, switch it on in the other half, and compare the results. Emory is also planning to conduct a blind trial.

The Cleveland-Brown group is even starting to think about next-generation versions of the technology. Rezai, for instance, envisions implanted sensors that could detect abnormal activity in key brain circuits and deliver the necessary jolts to correct it. With the help of Cleveland Clinic biomedical engineer Charles Steiner, he's also developing versatile electrodes that send current in a specific direction. These would create a more targeted pulse, enabling the psychiatrist to further fine-tune the stimulation to suit the patient.