Four years after publishing her research, Mayberg was ready to try what had never before been done: applying deep brain stimulation to Area 25.
DBS had been used since 1997 as a treatment for movement disorders, including essential tremor, Parkinson's disease and dystonia. Mayberg theorized the low voltage current from DBS could also help severely depressed patients.
Her first surgical experiment in 2003, in collaboration with neurosurgeon Dr. Andres Lozano at Toronto Western Hospital in Canada, was more about testing for safety than actually treating the patients.
"For all we knew, we were going to activate [the circuits] and actually make people feel worse," Mayberg explained.
The six patients who volunteered for the procedure had all tried and failed conventional treatments. Some had attempted or considered suicide.
"We had patients who were profoundly without any options and suffering," she said.
All six were lightly sedated when the holes were drilled and the electrodes implanted, but they were awake to describe what they experienced. Several patients reported profound changes just minutes after the stimulator was turned on. One said the room suddenly seemed brighter and colors were more intense. Another described heightened feelings of connectedness and a disappearance of the void.
The patients' descriptions during the procedure went far beyond anything the doctors expected.
One patient spontaneously talked about the first crocus blooms in early spring. Mayberg wondered if the procedure had triggered a hallucination or perhaps the electrode had touched a memory circuit. The patient explained it's the feeling of looking forward to something new and rejuvenating.
Mayberg says she struggled to remain a dispassionate scientist, but her empathy for the desperate patients who were, in effect, collaborators in the experiment got the best of her.