Finding the Treatment for Binge Eating and Addiction with Brain Zaps

“It may be that stimulation of the nucleus accumbens altered reward circuitry in the brain to decrease the volume of the pleasurable craving that patients with alcohol use disorder feel when they see or are around alcoholic beverages,” says Nir Lipsman, the principal investigator and neurosurgeon at Sunnybrook Health Sciences Centre.

Lipsman hopes to conduct a larger study to confirm the findings. His group is also interested in finding brain signatures linked to alcohol cravings, so stimulation may only be needed at certain times.

Scientists working in the DBS field believe that many psychiatric disorders may ultimately be amenable to therapy. For example, Sheth’s September review in the Journal of Neurology, Neurosurgery and Psychiatryry analyzed 34 studies of DBS used to treat OCD. He concluded that in 352 patients, it was effective in 66 percent of them.

But there are challenges in scaling therapy. Some psychiatric disorders, such as anorexia and bulimia, are difficult to replicate in mice. This makes it difficult to move forward with human research. And since doctors would target different parts of the brain depending on the condition, regulators want to make sure the technique is safe in each region before larger human trials get the green light. “It’s important to realize that this started with very well-controlled and planned mouse studies,” says Halpern. “We didn’t just operate directly on the human brain.”

The studies are also expensive – costing researchers around $100,000 per patient – and require complicated surgeries that pose risks for participants. Infections may occur after surgery or later develop at the site of the implanted lead. A misplaced electrode or a high pacing rate can cause mood swings. (One of the patients in the Toronto study became more irritable after receiving the brain implants. Once the researchers reduced the tension, the patient’s mood stabilized.) These challenges mean that the studies are often small and do not include a placebo group, making it difficult to draw broader conclusions about effectiveness.

They also need to take place over long periods of time so researchers can accurately gauge the effects of the stimulation – but it can be difficult to justify a long trial when patients don’t seem to be getting better. In the 2010s, two high-profile DBS studies on depression showed no improvement. In the smaller of the two studies, researchers measured patient response rates after just 16 weeks. The larger study was terminated early by its sponsor, St. Jude Medical, when an interim analysis found there was no benefit compared to a control group that received a sham device.

Helen Mayberg, a neurologist at Mount Sinai Health System in New York who pioneered the use of DBS for depression and was a consultant to the St. Jude study, says the decision to end the study early was a mistake. Her research over the past decade had shown that stimulating the subcallosal cingulum, also known as area 25, can relieve major depression. The region plays a role in appetite, self-esteem, sleep, and sadness processing, and has been shown to be hyperactive in some patients with major depression. However, later research by Mayberg and her colleagues found that many of the study’s patients who did not initially respond to therapy eventually improved.

She also believes the placement of the device has an impact on how well the therapy works. She remembers one of her patients who was no better after six months of stimulation. During the examination, the electrode was not inserted deeply enough. Once it was placed in the right place, the person’s symptoms began to improve. “We think this proves that location explains most of your variation in results,” Mayberg says.

Device maker Abbott, which acquired St. Jude Medical in 2017, is gearing up for a new study. Abbott’s system was recognized by the FDA in July as a breakthrough device for treating depression.

However, questions remain about which patients will benefit from DBS. Like Halpern, Mayberg and her team have collected brain recordings from major depressive patients and believe they have isolated a specific signature that indicates who will respond to therapy. But researchers are still trying to capture possible signals for other psychiatric disorders. “There’s this amazing promise at the same time, but so far untapped potential,” says George.