Breaking through the silence of the seemingly unconscious: Researchers read minds of the vegetative

British neuroscientist Martin Monti says he and his colleagues were "absolutely stunned" as they began to discover that by reading images of patients' brains while those patients were asked questions, the researchers could not only detect signs of life in the minds of patients thought to be vegetative, they could enable a patient locked in by injury to communicate.

Monti is the lead author of a widely hailed study published Wednesday in the New England Journal of Medicine's Early Online edition and detailed in an article here. In an interview, he described the process by which he and colleagues in Cambridge, Britain, and Liege, Belgium, broke through the silence of five grievously brain-injured patients who had been diagnosed as "vegetative" or (in one case) "minimally conscious."

Although those diagnoses assume that a patient is "wakeful without awareness," Monti and colleagues found that of 54 patients they tested, five were aware enough to respond to instructions to imagine playing tennis. Those patients responded with brain activity that looked just like that of healthy people thinking the same thing. Four of the vegetative patients showed brain activity suggesting the same level of awareness and intent when researchers asked them to imagine walking through the rooms of their home.

In one patient, then a 22-year-old man who had been thought vegetative since a car accident five years earlier, the researchers devised a way to get him to answer yes-or-no questions. By thinking about playing tennis, he responded -- correctly -- that, yes, one name provided by researcher was his father's first name. And by imagining navigating the rooms of his home, he responded "no" to simple questions about his siblings and family.

Monti said the researchers hope to use the technique to explore the minds of other "locked in" patients, such as those with amyotrophic lateral sclerosis, or Lou Gehrig's disease -- and to explore simpler techniques, such as EEGs to detect intent and awareness in patients thought to be vegetative.

He also said they hope to see the young man, now in his late 20s, again and use their brain-imaging techniques to communicate further with him. He said he is not haunted by the idea that, having seen flickering signs of mental life in the young man known as Subject No. 23, the researchers had to send him back to his silent world.

"I am proud we could give him a chance to tell us he was conscious, and to interact with his environment," said Monti, who said he hopes that techniques like those described in the study can be used to help patients tell their caregivers if they are in pain or distress. He added that the technique should improve the precision and accuracy of the techniques now used to diagnose patients who are unresponsive after head injury or illness that has blocked the flow of oxygen to their brains.

UCLA neuroscientist David A. Hovda, commenting on the study, noted that all but one of the patients who responded to the British-Belgian research team were young -- in their 20s -- and all of those who responded had suffered traumatic brain injury rather than stroke or illness that shut off the flow of oxygen to their brains.

That finding, he said, underscores two important things that the families of unresponsive patients will need to keep in mind: that traumatic brain injury, which kills 50,000 people a year and has left about 5.3 million Americans disabled, behaves differently from conditions that block oxygen flow to the brain, and may leave patients with more residual mental activity; and that younger brains are probably more resilient in the wake of injury than are older brains and may be more likely to show signs of awareness.

-- Melissa Healy

 

Rodent of the Week: Axons regenerate long after injury

Scientists have been working for more than a decade on methods to treat spinal cord injuries by attempting to regrow injured nerves. Some success has been achieved in animals that are treated immediately after the injury.

However, new research shows it's possible to coax the regeneration of nerve axons in rats as long as a year after injury. Axons are the part of the nerve that carries signals away from the nerve body. In the experiment, researchers were able to stimulate the growth of axons in the damaged part of the spinal cord and somewhat beyond the site.

It's difficult to get injured axons to grow because of scar tissue at the injury site, inflammation and chemical processes that inhibit the growth. Thus, the treatment was dependent on a complex and sophisticated process that included a cellular bridge to the injury site, a nervous-system growth factor to guide axons to the correct target and a stimulus to the injured neurons that turns on genes to promote growth.

Using this formula, researchers were able to demonstrate successful regeneration of axons. Rats that did not receive the full combination treatment did not exhibit growth.

"The good news is that when axons have been cut due to spinal cord injury, they can be coaxed to regenerate if a combination of treatments is applied," the lead author of the study, Dr. Mark Tuszynski of UC San Diego, said in a news release. "The chronically injured axon is not dead.

"While the regenerating axons grow for relatively short distances, even this degree of growth could be useful. For example, restoration of nerve function even one level below an injury in the neck might improve movement of a wrist or hand, providing greater quality of life or independence."

The study is published in the journal Neuron.

- Shari Roan

Photo credit: Advanced Cell Technology Inc.

A new approach to treating spinal cord injuries

Researchers focused on reversing the paralysis induced by spinal cord injuries have focused on using stem cells to regenerate the damaged nerve cells that are needed to transmit signals from the brain to the limbs.

Now a team of scientists from Switzerland, Russia and UCLA are reporting success with another approach. They used drugs and electrical currents to get paraplegic rats to walk again, according to a report published online Sunday by the journal Nature Neuroscience.

The animals were outfitted in a special harness to help them balance on their two hind legs. Then the researchers gave the rats medications that prompted “erratic hindlimb movements” by mimicking the effect of the neurotransmitter serotonin. When combined with small, carefully placed electric shocks, the rats’ legs moved in a way that resembled walking.

After nine weeks of practice, the paralyzed rats were able to resume normal hind-leg walking, the researchers said. The rats could also walk backwards and sideways and even run. These being Los Angeles rats, they naturally star in their own movie as well.

All this rehabilitation still left the animals unable to walk of their own accord, since their brains were still cut off from their legs. But human beings paralyzed by spinal cord injuries might be able to bridge that gap with neuroprosthetic devices, the scientists said in their study. The method could also improve walking in patients with Parkinson’s disease, they said.

-- Karen Kaplan

Video: This paralyzed rat learned to walk again … sort of. Credit: Gregoire Courtine et al

Rodent of the Week: Reconnecting axons in spinal cord injuries

For many years, researchers have toiled to find ways to heal the kinds of spinal cord injuries that lead to paralysis. In another step toward that goal, scientists at UC San Diego have demonstrated that regenerated axons -- the part of nerves needed to transmit signals -- can be guided to their correct targets to re-form neural connections.

Previous research has led to the ability to regenerate axons but researchers did not know how to coax the axons to grow into the correct target cells that would restore sensory functions.

"The ability to guide regenerating axons to a correct target after spinal cord injury has always been a point of crucial importance in contemplating translation of regeneration therapies to humans," the senior author of the report, Dr. Mark Tuszynski, said in a news release. "While our findings are very encouraging in this respect, they also highlight the complexity of restoring function in the injured spinal cord."

The researchers showed that regenerating axons can be guided to the correct targets using a type of chemical hormone called a growth factor. In the experiment, performed on rats, when the growth factor was placed in the correct target as a guidance cue, axons regenerated into it and formed synapses, the electrical connections that allow signals to travel. When the growth factor was placed in the wrong target, the axons grew in the wrong direction.

The synapses, however, were not electrically active, probably because the regenerating axons were not covered in myelin, the insulating material that protects nerves. "It appears that these regenerating axons require restoration of the myelin sheath to ultimately restore function," Tuszynski said.

That will be the next step in the team's research, he said. The paper is published online in Nature Neuroscience.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.