OS ANGELES — A team of physicians and neuroscientists on Wednesday reported the successful use of ultrasound waves to “jump start” the brain of a 25-year-old man recovering from coma — and plan to launch a much broader test of the technique, in hopes of finding a way to help at least some of the tens of thousands of patients in vegetative states.
The team, based at the University of California, Los Angeles, cautions that the evidence so far is thin: They have no way to know for sure whether the ultrasound stimulation made the difference for their young patient, or whether he spontaneously recovered by coincidence shortly after the therapy.
But the region of the brain they targeted with the ultrasound — the thalamus — has previously been shown to be important in restoring consciousness. In 2007, a 38-year-old man who had been minimally conscious for six years regained some functions after electrodes were implanted in his brain to stimulate the thalamus.
The ultrasound technique is a “good idea” that merits further study, said Dr. Nicholas Schiff, a pioneer in the field of using brain stimulation to restore consciousness who conducted the 2007 study. “It’s intriguing and it’s an interesting possibility,” said Schiff, a neuroscientist at Weill Cornell Medicine.
The UCLA procedure used an experimental device, about the size of a teacup saucer, to focus ultrasonic waves on the thalamus, two walnut-sized bulbs in the center of the brain that serve as a critical hub for information flow and help regulate consciousness and sleep.
“We found a way to jump start these circuits back into service,” said the study’s lead author, Martin M. Monti, a UCLA psychologist and neuroscientist who studies cognition and consciousness. He wrote up a case study, which was published online in the Journal of Brain Stimulation as a letter to the editor.
A brutal brain injury
That jump-started brain belongs to Bradley Crehan.
A recent college grad, Crehan was leaving a bar in Santa Monica last February when he was struck by a car. He suffered a severe brain injury when his head hit the pavement. “I’d probably had a little too much to drink and wasn’t looking,” he said, though he still has no memory of the accident or the weeks that followed.
Crehan had part of his skull removed to relieve pressure and was placed in a medically induced coma to allow his brain to heal. Doctors attempted to wake him after about a week, said his father, Michael Crehan, but it didn’t go well, so he was returned to the coma for another week. When he was brought out of that coma, he still wasn’t very responsive: He could reach for objects, make small spontaneous movements, and open and close his eyes as if sleeping and waking, but showed little comprehension and no ability to communicate.
“He was recovering but nobody could say for sure how the recovery would go,” Michael Crehan said. “They told us to expect five to six months in the hospital.”
Bradley Crehan has little memory of coming out of the coma. “My brain wasn’t functioning well enough for me to be confused,” he said. “I felt an indentation in my skull and wondered where I was. I wasn’t scared, just drowsy.”
The experimental treatment involved about five minutes worth of ultrasonic pulses targeting the thalamus; doctors used an MRI to precisely guide the sonic beam. A day after the treatment, Crehan started recognizing objects, attempted to use a spoon, and could blink on command, Monti said. Three days later, Crehan understood questions and could reliably gesture yes and no.
“He even gave me a fist bump when I was leaving,” Monti said. “He had emerged.”
Crehan’s recovery was swift and smooth. He left the hospital in four months, faster than anyone expected. “When I left, the nurses were saying, ‘Whoa, you’re leaving already?’” Crehan said.
He’s finished physical and occupational therapy and is now working to strengthen his memory. He’s driving, hitting the gym, applying for jobs, and hoping to enter the job market soon.
Monti cautions that the reason for Crehan’s recovery is unclear.
“We could have been very, very lucky that we did our procedure just as he was spontaneously recovering,” Monti said. “It could be he would have recovered anyway, and our stimulation did nothing.”
Crehan’s take: “I know I’m very lucky.”
His favorite University of California school, he said, is no longer his alma mater Santa Cruz, but UCLA.
A difficult field
Research into “disorders of consciousness” has been halting, for several reasons — starting with a lack of understanding of the workings of basic human consciousness.
Doctors have also been frustrated by the unpredictability of brain injuries; one severely injured patient might spontaneously emerge from a coma relatively intact, while others linger in vegetative states for years and sometimes decades. Still others remain in a minimally conscious state; they show some awareness and may be able to smile, cry, and even give yes or no responses, but cannot function on their own.
Further complicating matters: Determining a person’s level of awareness can be challenging because episodes of consciousness can be fleeting.
Monti, neuroscientist Adrian Owen, and other colleagues published a report in 2010 that found healthy-looking brain activity in patients in both vegetative and minimally conscious states. But experts still debate the extent of those patients’ awareness.
Large-scale trials have been conducted on two medications thought to help recovery. One is the sleeping aid Zolpidem, which sells under the brand name Ambien — and paradoxically, has been shown to ramp up brain activity in some vegetative patients. There have been a handful of amazing Ambien stories — people waking up to say “Hello, Mum” after years of silence — but a study of 60 patients with impaired consciousness failed to show any significant improvement on the drug.
Another drug that affects dopamine levels, Amantadine, was shown to speed recovery in a trial of 184 patients with impaired consciousness.
Researchers say it’s been difficult to get funding to study more ambitious treatments, such as implanting electrodes to stimulate the brain. It is also critical, they say, to include patients who have been minimally conscious or vegetative for years and are less likely to spontaneously recover. Crehan was treated just 19 days after his injury.
Cornell neuroscientist Schiff and his colleagues last month published a report of a second patient to receive thalamic brain stimulation via an implanted electrode: a 44-year-old male who had been minimally conscious for 21 years following a traumatic brain injury. This patient did not show the behavioral improvements that Schiff’s first patient did, but the scientists were able to detect systematic changes in the sleep and wake cycle, showing the patient’s brain did respond to the treatment despite the severity and length of his injury, Schiff said.
But that’s just a case study, not a full-scale clinical trial. Schiff estimated that a large study of his technique would cost $10 million to $12 million. “Honestly, when we went to the federal agencies, people didn’t want to pay for it,” he said.
Some of the ambivalence, he said, may stem from the fact that even when treatments restore some consciousness, patients may still be left severely impaired and bedridden. By some estimates, more than 100,000 patients in the United States alone are trapped in states of minimal consciousness; these patients are often viewed as all but dead, their families urged to withdraw life support and donate their organs.
Schiff and Monti, however, argue that restoring even some consciousness can lead to a huge improvement of quality of life for patients, their families, and their caregivers.
“Can you imagine,” Monti said, “a mother who doesn’t even know if her son can hear her?”
The ultrasound device used in the UCLA case was developed by Dr. Alexander Bystritsky, a professor of psychiatry at UCLA who directs the school’s anxiety disorders program. He developed it as a potential treatment for anxiety and other brain disorders, such as seizures, Alzheimer’s and Parkinson’s disease, and also as a research tool to probe the workings of the healthy brain.
Bystritsky has founded a privately held startup called Brainsonix in order to further develop the device and bring it to market. He donated the use of the device, but because of his role as manufacturer of the device, he was not allowed by UCLA to actively take part in the study.
“I was peeking from behind the door,” he said.
Monti said the portable device will make it much less costly to conduct trials on brain stimulation.
“Anyone could undergo this,” he said. “They have nothing to lose.”