After 22 years of failed treatments, including rehabilitation, psychotherapy and an array of psychiatric medications, a middle-aged Dutch man decided to take an extraordinary step to fight his heroin addiction. He underwent an experimental brain surgery called deep brain stimulation (DBS). At the University of Amsterdam, researchers bored small holes in his skull and guided two long, thin probes deep into his head. The ends of the probes were lined with small electrodes, which were positioned in his nucleus accumbens, a brain area near the base of the skull that is associated with addiction.
The scientists ran the connecting wires under his scalp, behind his ear and down to a battery pack sewn under the skin of his chest. Once turned on, the electrodes began delivering constant electrical pulses, much like a pacemaker, with the goal of altering the brain circuits thought to be causing his drug cravings. At first the stimulation intensified his desire for heroin, and he almost doubled his drug intake. But after the researchers adjusted the pulses, the cravings diminished, and he drastically cut down his heroin use.
Neurosurgeries are now being pursued for a variety of mental illnesses. Initially developed in the 1980s to treat movement disorders, including Parkinson's disease, DBS is today used to treat depression, dementia, obsessive-compulsive disorder, substance abuse and even obesity. Despite several success stories, many of these new ventures have attracted critics, and some skeptics have even called for an outright halt to this research.
One major misgiving is that recent applications may be outpacing their scientific support. Unlike the cautious early investigations of DBS for depression, carried out by neurologist Helen Mayberg of Emory University and her colleagues, the latest trials have been conducted less meticulously. Although these procedures are often considered low risk, as Mayberg once pointed out, “there is no such thing as minor brain surgery.”
Lobotomies are perhaps the most infamous example of “psychosurgery.” This procedure, which involved cutting the connections between different parts of the brain, has always been controversial. Only in the 1970s did concerns about its misuse drive these surgeries to extinction in the U.S. Similar techniques, such as freezing or cutting certain brain areas, persisted in China and Russia at least through the early 2000s.
DBS seems more palatable than these gruesome-sounding methods and rightly so. It is more precise: electrodes are guided to within a millimeter of their target to stimulate a specific brain area. DBS is also considered reversible because the electrical stimulation can easily be turned off. The risks of this procedure—including brain hemorrhage, infection or even death—are dire but uncommon.
The first brain area targeted for depression was chosen after years of painstaking neuroimaging research, but recent advancement in DBS has come as much from luck as from planning. Consider, for example, the serendipitous manner in which it was discovered that DBS might treat addiction. In 2006 psychiatrist Jens Kuhn of the University of Cologne in Germany and his colleagues tried DBS on a patient with a particularly bad case of panic disorder. The man's anxiety did not change, but he reduced his alcohol intake considerably without intending to do so. The researchers realized that in other experiments, stimulation to the same brain region, the nucleus accumbens, had also led to unintended, spontaneous reductions in drinking and smoking. Soon researchers were testing DBS on cocaine- and morphine-dependent rats, and in the past few years scattered reports of DBS for people with drug and alcohol problems have also emerged.
Other unintended side effects have also spurred new uses of this poorly understood technology. The case of obesity is instructive here. Despite not being a traditional mental disorder, obesity has become an enticing target for DBS. In 2013 neurosurgeon Donald Whiting of the West Penn Allegheny Health System and his colleagues reported that by stimulating the lateral hypothalamic area (the “feeding center” of the brain) of three people with intractable obesity, they could reduce their patients' urge to eat. Two of the three participants lost a significant amount of weight during the two-year study.[break]
At a different institution, DBS failed to help another man with obesity. Yet he experienced a surprising side effect as soon as the electrodes were turned on. Suddenly, he was overtaken by vivid memories from 30 years prior, and when the stimulation was increased his recollections became more intense. This man did not lose any weight (in part because he turned the device off at night to binge), but his experience made investigators curious about how stimulation might enhance memory. Now a larger experiment is under way to see if DBS can help reverse the effects of Alzheimer's disease. In this case, one man's unsuccessful surgery opened up a new avenue of research, but one could imagine a scenario in which the retrieval of painful memories brings back old trauma. Such potential risks underscore the uncertainty inherent to DBS today.
Cause for Caution
Indeed, some bioethicists contend that not enough is known about DBS to broaden its use so quickly, and they call for further studies in animal models and in better-understood conditions first. The selection of some stimulation sites, as in the Alzheimer's and addiction trials, has been driven not by theory so much as happenstance. Even the fundamental mechanisms of DBS remain elusive. Initially researchers thought that it produced the equivalent of a lesion by deactivating brain areas, but it is now clear that the effects are more complicated.
The quality of the trials themselves has also come into question. Recently single-person case reports have proliferated, which are less useful than larger, placebo-controlled clinical studies. The device maker Medtronic contributed to this trend when it obtained a “Humanitarian Device Exemption” from the Food and Drug Administration, which permits the company to apply DBS to obsessive-compulsive disorder. In doing so, Medtronic sidestepped the FDA's usual channels, which would have required more rigorous experiments to establish DBS's effectiveness for this illness.
A leading concern with this piecemeal approach is that it is not clear which patients are best suited to psychiatric DBS. In several cases, patients chose to receive a stimulator before they had tried all other treatments that might have assuaged their conditions. For example, the obese man who turned off his implant so that he could binge had declined bariatric surgery—in fact, he had justified his decision by arguing that he would continue to overeat after the procedure—so perhaps it is no surprise that he went on to fiddle with his device.
Ultimately the reason we do experiments at all is because questions remain about whether new techniques and technologies truly work. Case reports may not seem dangerous, especially when the procedure seems effective. Yet using DBS outside of careful clinical trials might obscure unknown risks or side effects, such as more subtle changes to someone's thinking or behavior. Further, successful trials are more likely to be published while unknown numbers of failed attempts go unreported, skewing our scientific understanding. The incentive to develop new psychiatric treatments is enormous—approximately 50 percent of people will meet criteria for a psychiatric disorder at some point in their life—but sound science must counterbalance this drive to expand DBS.
One last example: Spanish investigators recently used DBS in six people with intellectual disabilities to curtail their out-of-control aggressiveness. The intention was to prevent harmful behavior. Yet conducting brain surgery on individuals with mental disabilities will very likely alarm the public no matter the circumstances. The promise of psychiatric DBS is immense, but considering psychosurgery's dubious past, today's practitioners must proceed with caution.[break]
Misuse of the FDA's Humanitarian Device Exemption in Deep Brain Stimulation for Obsessive-Compulsive Disorder. Joseph J. Fins et al. in Health Affairs, Vol. 30, No. 2, pages 302–311; February 2011.
Proposals to Trial Deep Brain Stimulation to Treat Addiction Are Premature. Adrian Carter and Wayne Hall in Addiction, Vol. 106, No. 2, pages 235–237; February 2011.