From The Quarterly, Fall 2012
Earlier this year, in April, Dr. Sanjay Gupta, Chief Medical Correspondent for ‘CNN Presents,’ produced a special segment on deep brain stimulation (DBS). See the video at bbrfoundation.org/cnn-video.
Currently in clinical trials, the development of DBS to treat intractable depression can be traced back to the early work of a brilliant neurologist, Dr. Helen Mayberg. In 1991, Dr. Mayberg applied for—and received—a NARSAD Young Investigator Grant to pioneer work using functional neuroimaging (fMRI) to gain insight on brain function in depressed patients. She continued these studies for several years, receiving a NARSAD Independent Investigator Grant in 1995, and identified the subcallosal cingulate—Brodman Area 25—as an area appearing overactive in depressed people and a key target of antidepressant medications. Area 25 was already known to be a key conduit of neural traffic giving rise to emotion, but hadn’t been identified as a locus of depression pathology.
In 2002 Dr. Mayberg used a NARSAD Distinguished Investigator Grant to pilot the use of deep brain stimulation (DBS) to target Area 25 for the treatment of depression. DBS is often referred to as the ‘Pacemaker for the Brain’ as it applies pulses of current to regulate specific areas of the brain. Used since 1997 as a treatment for movement disorders such as Parkinson's disease, she hypothesized that stimulating Area 25 could regulate mood and help treat severely depressed patients that had not responded to other treatments. In her first study, after six months of stimulation, four of six patients were significantly better. She has since reported similar results for 31 other patients.
Recently, together with a NARSAD Young Investigator Grantee she mentored, Paul Holtzheimer, M.D., she met Edi Guyton as a potential participant for the new Emory DBS research study.
Edi was selected for the experiment on February 23, 2007. She was rolled into a surgical suite, the doctors studied computer-enhanced images of her brain and two holes were drilled into her skull. As the DBS electrodes were positioned on each side of her brain, the doctors were able to monitor the sound of neurons firing. Finding which contact works best is done through trial and error as the patient describes changes in behavior and thinking with short bursts of stimulation. As a benchmark, Edi was asked to rate her feelings of dread on a scale of 1 to 10. "Eight," she reported. Two minutes later, with contact No. 1 on, Edi said, "Three." But doctors would get an ever better result with contact No. 2. Shortly after the second contact was turned on, Edi quietly announced, "I almost smiled." Then she chuckled. Dr. Holtzheimer asked, "Did something strike you as funny? Or was it just sort of spontaneous?" "I was thinking about playing with my grand-niece," Edi replied. "That was when I almost smiled. But when I laughed, that was because I almost smiled."
Five years after the surgery, Edi Guyton is one of Dr. Mayberg's many success stories. While Dr. Mayberg does not yet fully understand how DBS works or why some patients respond to DBS and others do not, she continues to lead experimental studies at Emory to address these critical questions. Does the electricity from DBS activate neurons near Area 25 or inhibit them? Is DBS flipping a switch or knocking down a wall? What regions connected to Area 25 might be critically involved? "We still have a lot to learn about the physiological changes associated with stimulation, but we now have new clues as to where to look,” Dr. Mayberg says. “Our goal is to improve on our 60% response rate, and our new research strategies will hopefully provide important new insights towards this objective.”