Happiness is a Warm Electrode?

The most promising new treatment for severe depression isn't a pill. It's a permanent implant that shocks the brain. Is this what joy looks like?

In the middle of room #11 in the Cleveland Clinic's surgical center, Diane Hire lies on an operating table, the back half of her shaven head hidden behind a plastic curtain. Four pins, one driven into either side of her forehead, the other two in back, hold a titanium halo fast to her skull. An anesthesiologist, several nurses and her psychiatrist cluster around the bed.

Behind the curtain, neurosurgeon Ali R. Rezai surveys Hire's brain, white and snaked with thin red arteries, through a pair of small holes he's drilled in the top of her skull. Because so few pain receptors are located in the brain, only local anesthetic numbs Hire's head. She is awake during the procedure-or as awake as she can be. For the past 20 years, she has suffered from severe depression, a crippling strain of the disease that afflicts as many as four million people. Years of therapy, at least 10 different drugs and six courses of the whole-brain shock technique known as electroconvulsive therapy (ECT) all failed to bring Hire lasting relief.
Her final hope is this operation, a radical form of neurosurgery called deep-brain stimulation, or DBS. Whereas ECT-a treatment that's been demonized in movies like One Flew over the Cuckoo's Nest but is still used on roughly 100,000 patients a year-floods the brain with electricity from the outside, this technique delivers a smaller dose of better-targeted current to an area of the brain believed to be a key regulator of mood. Wires thread beneath the skin from their place in the brain and plug into two battery-run stimulators implanted in the chest. About the size of an iPod nano, each stimulator constantly pumps out current, bathing a small region of brain tissue in electricity. If ECT is the equivalent of slapping defibrillators against a heart-attack victim's chest, deep-brain stimulation is the pacemaker that prevents the attack in the first place.

On the operating table, Hire closes her eyes. Rezai slowly inserts a wire as thin as a fishing line through the left hole in her skull, using the halo as a guide. His team has already mapped out his route using a precise 3-D reconstruction of Hire's brain compiled from 180 MRI scans. His target is a chunk of neurons associated with energy and mood. After the tip of the wire is in the right spot, he repeats the process on the other side.
Within 90 minutes of the first cut, Hire has two electrodes lodged in the center of her brain. Now it's time to charge them up. On the other side of the curtain, Donald A. Malone, Jr., Hire's psychiatrist, tells her that everything's ready. Malone has a clear, soothing voice and a comforting, boyish face. He's the kind of person you'd want to talk to if someone was about to shock your brain.

At his signal, two volts of electricity, enough to power a wristwatch, course through the wires and radiate outward from the tip a few millimeters in every direction. Millions of neurons bask in the electricity, and the effect is fairly immediate. Hire feels warm at first, a bit flushed.

And then it happens. The room looks brighter to her. The faces, the big, circular lights overhead, the ceiling-they all seem clearer. Malone asks her how she feels. "I'm really happy," she replies, clearly surprised. "I feel like I could get up and do all sorts of things." But even more telling than her words is the look on her face. For the first time in 20 years, with a halo bolted to her head and two freshly drilled holes in her skull, Hire smiles.

Prescription Voltage

Deep-brain stimulation began as a treatment for movement disorders in the mid-1990s, and the surgery has been performed on more than 40,000 patients, most of them Parkinson's sufferers, since then. In those cases, the current normalizes activity in the basal ganglia and thalmus-which dictate motor control, among other things-and can calm their shaking hands and limbs.

But the clinical trial in which Hire is enrolled, along with 16 other patients, is among the first to tackle depression. Other major trials are under way at Emory University and the University of Toronto. Exact numbers are hard to ascertain, but it's estimated that fewer than 50 patients in North America are walking around with wires in their brain.

In some ways, severe depression is a far more challenging disease to treat than Parkinson's. It can manifest in dozens of different ways and arises from a variety of complex factors, some genetic and some environmental. For instance, scientists are just starting to identify a class of what they call vulnerability genes. In essence, they come in two forms: lucky and unlucky. "If you have one version, you are relatively resilient in the face of stress," says Brown University psychiatrist Ben Greenberg, who is collaborating with the Cleveland Clinic group. "But if you have another, the more severe the stress you have in your life, the more likely you are to develop depression."

Most depression therapies address the disease as a kind of communications problem in the brain. When all is healthy, a neuron receives a chemical message from a neighboring neuron and dispatches a corresponding electrical signal along a nerve fiber called an axon. Then, at the other end, the neuron pumps chemicals on to the next cells.

Drugs attempt to improve communication by altering chemical signals. Prozac, the popular antidepressant, blocks the action of a pump that sucks serotonin, a key mood-regulating chemical, out of the gaps between two neurons. This leaves more serotonin in those spaces, supposedly improving the flow of messages between neurons. But why (or whether) this makes people happy remains unclear. Antidepressants may generate billions of dollars in revenue for pharmaceutical companies, but recent studies suggest that pills work only 50 percent of the time-and they don't do much at all for the millions like Hire who are severely depressed.

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http://www.popsci.com/scitech/article/2007-09/happiness-warm-electrode