26 July 2012
Treating disease by stimulating brain cells with light is a step closer to reality following the first demonstration that the technique can improve mental performance in monkeys. Two monkeys performed better on simple computer tasks after light was used to boost the activity of brain cells necessary for the task.
“For the first time, we were able to change behaviour in primates with our technique,” says Wim Vanduffel of Massachusetts General Hospital in Charlestown, who is head of the group that performed the experiment.
Known as optogenetics, the method has the potential to treat conditions such as epilepsy, where the light could temporarily deactivate the brain cells that cause seizures, or Parkinson’s disease, where it can activate cells that make dopamine, the neurotransmitter vital for controlling mobility that those with Parkinson’s lack.
Previously, it has been used in nematode worms to trigger them to lay eggs, and mice to relieve depression and paralysis. Researchers have also used it in monkeys, but only on single, isolated neurons. Vanduffel and his colleagues wanted to see if they could extend this to entire networks of cells, boosting a monkey’s ability to perform a simple computer-based task.
Natural performance enhancers
First, Vanduffel’s team scanned the two monkeys’ brains using functional magnetic resonance imaging while they followed a green dot on a computer screen. From the scans, the researchers could tell that the monkeys relied on an area of the brain called the arcuate sulcus to do the task.
Next, the team inserted a gene that reacts to light into the cells of the arcuate sulcus. Originally from algae, the gene makes a protein called channelrhodopsin-2, which reacts to blue light by admitting ions into the brain cells, activating them in the process. They gene was ferried into the cells using a virus.
Finally, the team guided fine, light-conducting needles into the same area through a port permanently attached to the animal’s skull. The monkeys then repeated the task as the researchers pumped light into their brains.
Comparisons of the monkeys’ performances before and after the treatment showed that they reacted about 10 per cent faster when undergoing light stimulation. “One monkey reacted about 20 to 28 milliseconds faster, and the other about 15 milliseconds faster,” says Vanduffel.
Vanduffel says that in unpublished experiments, monkeys undergoing the technique while carrying out a more complex task improved even further. “My hunch is that the harder the task, the more significant the effect,” he says.
Proof of principle
“This is just proof of principle, and there’s a very, very long way to go before we can start using it in humans,” he adds.
Although treating humans is a distant prospect for now, Vanduffel says the method is evolving fast. Gene switches have been identified that work in very specific brain areas, potentially enabling light to target unhealthy cells without disrupting healthy ones.
“This work is exciting because they’ve shown that pre-stimulating an area of the brain necessary for the task makes processing faster,” says Arnd Pralle of the State University of New York at Buffalo, who uses magnetism instead of light to activate brain cells in worms.
Another important advance, says Pralle, is that whole networks of cells were activated for the first time, compared with single or small groups of neurons stimulated in previous monkey and rodent experiments.
Journal reference: Current Biology, DOI: 10.1016/j.cub.2012.07.023.