A Tiny Electric Brain Implant Could Wake People in Comas
Unconscious monkeys zapped in one area of the brain suddenly woke up
Last year, a woman from the United Arab Emirates woke up in a German hospital after a road accident in 1991 left her in a coma for 27 years. Her doctors couldn’t believe it.
Her case was exceedingly rare. Only a handful of other patients have ever recovered after that long. Some people may gradually come out of a coma or wake up after a few weeks. Some become what’s known as “minimally conscious,” showing occasional awareness and responsiveness. Others may enter a vegetative state — where they seem awake but show no signs of awareness. These patients may eventually regain a degree of awareness, but they could also remain in a vegetative state for years.
To help these people, scientists have been trying to pinpoint where consciousness resides in the human brain. Doing so would not only solve one of the central questions of neuroscience, but it could also lead to treatments to “awaken” people in comas.
Brain scans have suggested that an area called the thalamus, which is located just above the brain stem, plays a role in consciousness. In a paper published in the journal Neuron on Wednesday, researchers at the University of Wisconsin-Madison identified a tiny zone within this region — just a few millimeters in size — that, when stimulated appropriately, appears to wake unconscious monkeys. It may be especially important in keeping humans awake and conscious as well.
First, the researchers inserted electrodes in the brains of macaques, recording activity from multiple brain areas at a time. By studying animals when they were awake, sleeping, or anesthetized, they narrowed down the region that seemed to be involved in consciousness to an area within the thalamus, only 1–1.5 millimeters across and 3–4 millimeters deep, called the central lateral thalamus.
Then, they used an approach called deep brain stimulation on anesthetized monkeys to deliver electrical pulses to this region. Deep brain stimulation, which involves surgically inserting electrodes into the brain to administer intermittent electric stimulation, is an approved treatment for Parkinson’s disease and a handful of other conditions. It has also been tried in some comatose patients but has only helped a few people.
“The animal looked around the room as if it was coming out of anesthesia normally.”
In contrast to those attempts, the Wisconsin team used much smaller electrodes to precisely target the central lateral thalamus. They also designed the electrodes to match this region’s shape. When they flipped on the stimulation, it had an immediate effect on the monkeys.
“Within about two seconds of starting stimulation, the animals started to open their eyes, make body movements and purposeful reaches,” says Yuri Saalmann, an assistant professor of psychology at the University of Wisconsin-Madison and senior author of the paper. “The animal looked around the room as if it was coming out of anesthesia normally, despite the fact that there was a continuous administration of a relatively steep dose of anesthesia.”
When the stimulation was turned off, the monkeys went back into an unconscious state within seconds.
In 2007, a group at Weill Cornell Medical College led by neuroscientist Nicholas Schiff reported that deep brain stimulation to the general thalamus area roused a patient from a minimally conscious state, restoring limited movement and speech. Stimulation to the thalamus has since improved a few other patients’ conditions, but it hasn’t worked across the board for people in comas. The new study suggests targeting just the central lateral thalamus may be helpful where general thalamus stimulation is not.
“It is a very tough area to target,” Saalmann says of the central lateral thalamus. That may explain why only a handful of patients with disorders of consciousness have benefited from brain stimulation while many others have not.
There was another key difference in the stimulation approach that Saalmann’s team used compared to previous studies that have attempted to awaken unconscious patients. Deep brain stimulation studies typically use a high frequency of electricity — 100 hertz, or 100 electrical pulses a second. Saalmann’s group used a frequency half that amount because they had observed that neurons in the central lateral thalamus generated electrical pulses at only 50 hertz.
“We basically tried to mimic the activity of the neurons in the central lateral thalamus in the wake state,” Saalmann says. They tried higher and lower frequencies, too, but they weren’t effective.
Before the approach can be tried in comatose patients, Saalmann’s team needs to do more animal studies. They’re planning to do experiments to see if they can keep monkeys conscious for longer to do certain tasks like playing video games. He hopes to move the approach to clinical trials in comatose patients within a few years.
Meanwhile, a few ongoing clinical trials are testing the effectiveness of noninvasive types of stimulation, like transcranial direct current stimulation and vagus nerve stimulation on people in comas. Neuroscientists are also exploring the use of ultrasound, which was used to wake up a man in a coma.
Aaron Boes, a neurologist at the University of Iowa, says the Wisconsin group’s findings are promising, but whether the central lateral thalamus is the best area to target in people with disorders of consciousness is still an open question. “I suspect there are many areas of the brain that can modulate the level of arousal,” he says.
Martin Monti, an associate professor of neurology at the University of California, Los Angeles, thinks different types of stimulation are worth pursuing, but cautions that it may not work for everyone. His group is testing ultrasonic and non-invasive stimulation of the thalamus, but he says that brain damage in some patients may be so pervasive that stimulation won’t be effective at all.
“The patients who are in a disorder of consciousness typically narrowly survived a catastrophic life event,” he says. “So, it is not as simple as turning consciousness back on.”