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Biomedicine

Jump-Starting the Damaged Brain

Electrical stimulation restores brain function in a minimally conscious patient.

Scientists have shown that electrically stimulating part of the brain can improve both mental and physical function in a patient with severe brain injury. The findings are a major step forward for the largely neglected group of patients who suffer serious impairments in consciousness that persist long after their initial injuries.

Zapping the brain: Surgically implanted electrodes in the brain of a man with severe head injuries are connected to a pair of surgically implanted pacemakers. An illustration of the device is shown above. The programmable pacemakers deliver electricity to the brain via the electrodes, sparking activity in the brain. Researchers say that boosting activity in the thalamus, shown in close-up in the bottom image, improved both motor and cognitive function in this patient.

“He can eat, speak, watch a movie, and drink from a cup,” said the patient’s mother, who chose to remain anonymous, at a press conference on Wednesday held by the journal Nature, which published the study. Before her son, 38, participated in the study, she said that he had spent five years in a nursing home, where he was unable to eat and appeared largely unaware of his surroundings. “Now he can cry and he can laugh,” she said. “He can say ‘Mommy’ and ‘Pop.’”

In 1999, the woman’s son suffered serious brain injuries after being robbed and beaten, his skull crushed. Following life-saving surgery, he remained in what neurologists call a minimally conscious state–a clinical category somewhere in the gray area between coma and consciousness. Unlike vegetative patients, who are defined as those totally unaware of their environment, patients in a minimally conscious state may occasionally and unreliably laugh or cry, reach for objects, or even respond to simple questions. Few reliable estimates exist on the number of people with this condition, but some researchers predict that there are as many as 280,000 minimally conscious patients in the United States.

Previous research on these patients suggests that some have a surprising level of brain activity. (See “Raising Consciousness.”) Scientists theorize that some of the patients’ neural circuits are left intact, occasionally becoming active or coordinated enough to allow the patients to respond to their environment. “We thought patients in this state might benefit [from stimulation] because they have the elements of language capability,” said Nicholas Schiff, a neurologist and researcher at Weill Cornell Medical College, in New York, and one of the lead scientists on the study, at the press conference. “That shows that the intrinsic brain systems may be there and could potentially be restored.”

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Schiff and his colleagues employed a procedure called deep brain stimulation, which has been successfully used to treat thousands of people with Parkinson’s disease and is currently in clinical trials for the treatment of depression, epilepsy, and chronic pain. Electrodes are surgically implanted into a specific part of the brain–the exact location depends on the condition–and connected via wires to a programmable pacemaker implanted in the chest. Doctors can then turn the device on and off, sending precise amounts of electrical current into the brain.

In the case of the minimally conscious patient, doctors targeted part of the thalamus, a structure that sits deep in the brain atop the brain stem. The thalamus transmits sensory information to other parts of the brain and plays a key role in regulating arousal. “These cells have wide projections to the cerebral cortex and basal ganglia, and have the capacity to increase brain activation globally,” said Schiff. This part of the brain has also been shown to play a key role in disorders of consciousness. Scientists theorize that the targeted electrical current stimulates the resident cells and potentially the circuits to which they are connected.

According to the researchers, the patient’s behavior changed as soon as the device was switched on. “Prior to the trial, he was in a sort of chronic state of under-arousal,” Joseph Giacino, a neuropsychologist at the JFK Johnson Rehabilitation Institute, in Edison, NJ, and lead scientist on the study, said at the press conference. He usually kept his eyes closed even though he was awake, and he rarely mouthed a single word. After the procedure, said Giacino, “most striking to us was that he regained normal eye opening. He turned his head and focused on the person speaking to him.”

The researchers analyzed the patient’s behavior over the next six months, turning the device on and off to assess its impact. They found that improvements in motor and cognitive function were clearly linked to the electrical boost. The patient also showed a slow but steady gain in function even when the device was turned off. The findings are particularly noteworthy because they show a benefit so long after the initial injury, says James Bernat, a neurologist at Dartmouth Medical School who was not involved in the study.

While the official test period is over, the patient continues to receive the electric stimulation in 12-hour cycles–to correspond with the sleep-wake cycle–and he continues to get better. “Now he can consistently respond verbally when he is prompted,” said Giacino. “The most recent change is that he’s able to say the first 16 words of the Pledge of Allegiance.”

Still, the team cautions that it’s too early to predict how well deep brain stimulation will work on other minimally conscious patients. Success is likely to depend on the precise nature of the injury, and on whether some of the critical neural circuits remain intact. At the conference, Schiff said he suspects that there will be many patients in a minimally conscious state who will not benefit.

The researchers are planning to surgically implant devices in 11 additional patients, which should give them a better sense of how well the treatment might work in the larger patient pool. If successful, the technology might eventually be applicable to a broader group of brain-injury patients, says Ali Rezi, a neurosurgeon at the Cleveland Clinic Center for Neurological Restoration who performed the surgery. Head-trauma patients with less severe impairments may one day benefit as well, he says.

For the moment, Schiff and others hope that the findings will bring new focus on a group of patients who have largely been given up on, receiving only custodial care. “Most patients who show [minimally conscious state] behaviors are essentially discounted from further medical treatment,” said Schiff. “But there may be patients that harbor greater reserves. That’s what pushed our interest.”

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