Electrical brain stimulation, in contrast, targets the neural circuitry. Brain disorders, including depression, are thought to result when the electrical signals that travel through neural circuits are disrupted in a particular region. ECT induces a seizure that, in a way still not fully understood, resets the circuitry of large regions of the brain, possibly restoring the proper release and uptake of neurotransmitters. But in causing a seizure, ECT acts like a blunt instrument, sending a large current through the skull, basically to see what happens. Nonconvulsive devices hold promise because they attempt to achieve the same results by targeting a pivotal place, without inducing a seizure.
The new options are all variations on the ECT theme of using electricity to change the pattern of brain activity. Several of them work on specific regions of the brain that research has linked to abnormalities, and all stimulate the brain with lower doses of energy than ECT, and without causing seizures. Their efficacy depends on the brain’s plasticity, its ability to be remodeled by learning, experience, drugs—and electricity.
Vagus nerve stimulation, which the FDA approved as a complementary treatment for long-term management of treatment-resistant depression just last year, uses a back door to the brain. The vagus nerve, one of the body’s 12 cranial nerves, threads its way through far-flung regions of the body, sending signals to and from the digestive tract, stomach, heart and other places, through the neck and into the brain, where messages are relayed to the widely distributed limbic system, beneath the outer cerebral cortex. While the cortex governs higher-order cognitive processes, the limbic system helps rule emotions. It includes the hypothalamus, hippocampus, amygdala and other regions, to which we owe our feelings of fear, anxiety and sadness, as well as drive and motivation. The brain stem produces the bulk of the mood-regulating neurotransmitters serotonin, dopamine and norepinephrine, which are central to communication in the limbic system. Stimulating the vagus nerve helps gain access to those brain regions and systemically influences the neurotransmitters.
In 1999, in a pilot study, Karmen McGuffee of Garland, Texas, another of Husain’s patients, was fitted with a two-part VNS device. Electrodes were attached, via a quarter-inch incision, to the vagus nerve in her neck. Then wires were threaded down to her chest, where a small hockey-puck-shaped disk was implanted beneath the skin. The disk sends pulses to the electrodes at the vagus nerve, much the way a cardiac pacemaker regulates the heart. Husain can adjust the settings using a handheld device that functions like an electronic prescription pad, delivering the correct dosage of milliamps. If something goes wrong, the device can be turned off in an instant. But for McGuffee, it has remained on—even through her pregnancy and the delivery of a child in 2003—and to heartening effect. She is among the 15% of patients in the Phase III trial of VNS who ceased to be clinically depressed. (Another 27% saw their symptoms reduced by at least half.)
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