Ever feel like you could use a little jolt to perk up your brain? Six epilepsy patients recently got exactly that. While they were in the hospital awaiting surgery to mitigate their seizures, they volunteered for an unusual experiment: Taking advantage of platinum electrodes surgeons had implanted in the patients' brains, researchers zapped the volunteers with mild pulses of electrical current. The jolts enhanced the patients' ability to learn their way around a virtual city.
"It's an amazing experiment embedded in the routine care of these patients," says Helen Mayberg, a neurologist at Emory University in Atlanta, who was not involved in the study. The implanted electrodes help surgeons locate the source of a patient's seizures before operating to remove it. Mayberg and others say the findings provide insight into the neural mechanisms of memory and raise the possibility of using such deep brain stimulation (DBS) to stave off memory loss in people with early stages of Alzheimer's disease.
In the study, the patients were given a laptop and asked to play a taxi driver game. They used a joystick to navigate around a virtual city, picking up passengers and dropping them off at various locations. Unbeknownst to the patients, the researchers stimulated their brains when they found their way to certain destinations for the first time. When the patients later made another taxi run, the researchers watched to see if they took a shorter route to those destinations the second time around.
They did. When the team had stimulated the entorhinal cortex, a component of the brain's memory circuitry, while patients first learned their way to a destination, the patients took a more direct route to that destination and got there faster on the second try, compared with destinations they'd learned with the electrodes switched off, the researchers report today in The New England Journal of Medicine. Stimulating the hippocampus, a nearby brain region also crucial for memory, did not have a consistent effect and even seemed to inhibit learning in some cases.
"It's a fascinating result," says Richard Morris, a neuroscientist who studies memory at the University of Edinburgh in the United Kingdom. The entorhinal cortex is the major conduit of information from other parts of the brain into the hippocampus, and Morris thinks it makes sense that stimulating this region might somehow make the memory circuit work better. The neural circuitry within the hippocampus itself is more complicated, Morris says, which could explain why stimulating that part of the brain yielded mixed results.
Study leader Itzhak Fried, a neurosurgeon at the University of California, Los Angeles, says he's interested in investigating entorhinal stimulation as a treatment for Alzheimer's disease or other memory disorders. But many questions need to be answered. The new study demonstrates improvements in only spatial learning, Fried notes. Whether it could enhance memory for events, say, or names and faces remains to be tested. Future studies should also investigate whether stimulating the entorhinal cortex while people try to recall a memory might have beneficial effects as well, Fried says.
Tens of thousands of patients with Parkinson's disease and other movement disorders have benefitted from DBS, and Mayberg and others have been investigating its use for depression and other psychiatric disorders. But whether and how such a treatment would work for memory problems is still far from clear.
One pilot study of DBS in six people with early-stage Alzheimer's disease was published in 2010 by neurosurgeon Andres Lozano and colleagues at the University of Toronto in Canada. They stimulated yet another component of the brain's memory circuitry, the fornix, with mixed results. One patient exhibited improved memory, two declined more slowly than expected, and three others showed no significant effect. "In two of our patients with Alzheimer's we were able to stimulate and get déjà vu memories of events that had happened 20 or 30 years earlier," Lozano says. His team hopes to begin a clinical trial later this year that would enroll about 50 early Alzheimer's patients.
In the meantime, Lozano says several apparently healthy people have e-mailed him to inquire about memory-enhancing surgery. He turns them down. "It's totally off the table," he says. Too little is known at this point about the long-term safety and effects of DBS to justify the risks of surgery in healthy people, he says. So at least for now, if you're feeling like you need a jolt, you may have to settle for a cup of coffee.