Setting aside the bowl-of-soup model did not mean deciding that neurochemicals weren't important. Rather it meant deciding that neurochemistry, and particularly the chemistry dictating how individual neurons communicate with one another, was probably driven by traffic between different brain areas, and that identifying the patterns in that traffic might yield new understanding. (Or, using another metaphor, if the brain is an orchestra, then the neurochemical approach focuses on how well individual players listen and respond to the players adjacent to them; the network approach, like a conductor, focuses on how the orchestra's sections -- strings, winds, brass, etc. -- coordinate and balance volume and tone. When both are working well, you've got music.)

Imaging tools for tracking these relationships, like PET scans and later functional magnetic resonance imagery, were just maturing as Mayberg pursued her work. Neuroscientists were soon using these tools to help identify networks involved in mental processes ranging from distinguishing facial expressions to experiencing alarm or pleasure. Each of these networks engages different brain areas in different combinations. The areas active in recognizing a fearful expression, for instance, won't match those for recalling old memories, though some areas might overlap. Defining the network involved in any given process requires figuring out not just which parts are involved but also which parts are most vital and how one affects another.

By the 1990's, Mayberg was trying to define the network that goes awry in depression. She and other researchers soon established that depression involved abnormal patterns of activity in a network that includes limbic areas (a cluster of evolutionarily older brain areas around the top of the brain stem), which control basic emotions and drives like fear, lust and hunger, and the newer cortex and subcortex responsible for thought, memory, motivation and reward.

Several researchers were working on this. But Mayberg, and, separately, Dr. Wayne Drevets, then at Washington University and now at the N.I.M.H., increasingly homed in on Area 25, which seemed crucial in both its behavior and its position in this network. They found that Area 25 was smaller in most depressed patients; that it lighted up in every form of depression and also in nondepressed people who intentionally pondered sad things; that it dimmed when depression was successfully treated; and that it was heavily wired to brain areas modulating fear, learning, memory, sleep, libido, motivation, reward and other functions that went fritzy in the depressed. It seemed to be a sort of junction box, in short, whose malfunction might be "necessary and sufficient," as Mayberg put it, to turn the world dim. Maybe it could provide a switch that would brighten the dark.

To work the switch, Mayberg needed a knife. In 1999 she moved from the University of Texas at San Antonio to the University of Toronto, where she met Lozano, who had become expert at using deep brain stimulation for treating Parkinson's, the neurological affliction that causes tremors and rigidity as well as cognitive and emotional declines. By the time he and Mayberg met, he'd slipped electrodes into the brains of almost 300 patients.

Depression is more elusive than Parkinson's. But approaching Area 25 with D.B.S. allowed the researchers to use a known tool. Neurosurgeons found as early as the 1950's that they could treat Parkinson's by destroying a small portion of the hyperactive globus pallidus, a brain area that is crucial to movement. The treatment illustrated one of the brain's many oddities: some areas can cause more trouble when they are excessively active than when they have no activity at all. In the early 1990's, surgeons increasingly began to use D.B.S. to quiet the globus pallidus by sending it steady, rapid pulses of low voltage. Patients' tremors would instantly ease or cease; their rigidity and uncontrollable body movements would fade over a week or two. Killing the current revived the symptoms. Surgeons have now implanted D.B.S. electrodes in some 30,000 Parkinson's patients worldwide. The procedure is not a cure-all. It helps some patients less than others, does little to alleviate Parkinson's cognitive and emotional decay and occasionally creates complications including infection, bleeding and memory loss. Its biggest problem may be its success. So many medical centers now do it that some do it badly or on poorly qualified patients. But done well, it usually works.

Mayberg knew all this from the literature and learned more in conversations with Lozano. She grew increasingly convinced that applying D.B.S. to Area 25 might control depression.