Use of Deep Brain Stimulation Widens
Treatment's promise moves beyond movement disorders


by Tom Valeo

May, 2008

Electrically stimulating the hypothalamus of a morbidly obese man failed to curb his appetite, but jogged his memory instead, and that has pushed researchers to study whether the technique may hold promise for bolstering the failing memory of people with Alzheimer’s disease. The incident, reported in January, adds to the list of brain disorders in which deep brain stimulation, or DBS, is being used or tested.

At least 40,000 Parkinson’s patients have received DBS to quell the tremors and other symptoms of the disease. One study by German investigators found DBS so effective that they recommended it as the treatment of choice for Parkinson’s patients with severe symptoms no longer responsive to medication.

Helen Mayberg, a professor of psychiatry at Emory University, has found that DBS of “area 25,” located behind the frontal lobes, alleviates the profound sadness in some patients suffering from intractable depression. Eight of her first 12 depressed patients to receive DBS experienced significant relief. The first one’s depression seemed to lift the moment the stimulator was switched on, and it returned when it was shut off without her knowledge.

Mayberg’s “network model” of depression attributes the disorder to faulty connections among various brain areas. Area 25, for example, is wired to brain areas involved with fear, learning, memory, sleep, sexual desire, motivation and other functions that falter in the depressed.

Other researchers have shown that DBS can reduce the symptoms of Tourette’s syndrome, cluster headaches, obsessive-compulsive disorder, and phantom limb pain. One man who had been in a minimally conscious state for six years following a car accident opened his eyes and started to communicate after receiving DBS of his thalamus.

Memory Mystery

No one knows just how DBS makes a difference, but the dramatic effect that the procedure had on the obese man’s memory may provide a clue.

As soon as the stimulator, implanted under the skin of his upper chest, sent the first signals to the electrodes planted in his hypothalamus, the man reported a vivid sense of what he called “déjà vu.” He saw himself with friends in a park 30 years earlier. He heard them talking, although he could not make out what they were saying, and he saw his girlfriend at the time. When the voltage was increased, the scene became more vivid.

Even more striking, the man’s working memory improved significantly. Before surgery he could recall about 43 percent of the words read to him in one test. When the stimulator was on, he could recall about 70 percent, but his performance dropped to pre-surgery levels when it was turned off. His IQ also increased by 9 points when he was tested with the stimulator.

“I’ve talked to other neurologists and no one understands this report,” says Larry R. Squire, a professor of psychiatry, neurosciences and psychology at the University of California, San Diego, who studies the neural basis of memory. “You’d think that when you stimulate those areas you’d disorganize them. The idea that you could improve memory is pretty surprising.”

The answer may lie in the hippocampus, the brain structure crucial to the creation of short-term memories, rather than the hypothalamus, which received the stimulation.

Mahlon R. DeLong, a professor of neurology at Emory University, who studies the causes of Parkinson’s, suspects that the electrical stimulation delivered to the hypothalamus may be reaching the hippocampus, which is vital for memory formation. Andreas Lozano, the surgeon who implanted the electrodes, and his co-authors expressed the same suspicion in their paper in the Annals of Neurology about DBS of the obese man’s hypothalamus. They believe the stimulation may travel from the hypothalamus to the hippocampus along the fornix, a bundle of fibers that passes near both areas.

“This is the so-called fiber of passage problem,” DeLong says. “The stimulation may not be acting locally; it may be activating axons that go to other regions of the brain.”

The stimulation of the hypothalamus might also increase attention and vigilance, he says, which could improve memory.

Lozano already has performed the same type of DBS on six people with Alzheimer’s disease and plans to add three more as part of a clinical study.

“We don’t know if it will work,” Lozano told the Independent of London after the first three surgeries. “We want to assess if we can reach the memory circuits and drive improvement. It is a novel approach.”

Whatever the explanation, the prospect of improving brain function with DBS is sure to raise questions about what DeLong calls the “ethics of enhancement.”

“I think everybody wants to function optimally and they are willing to take things that will push them above where they are,” he says, referring, for example, to college students who take methylphenidate (Ritalin), modafinil (Provigil) or other drugs to improve their alertness and concentration when they study.

In the meantime, DBS will certainly reveal more about the brain.

“For generations we have learned about brain function by observing the effects of lesions produced by tumors, strokes and so on,” DeLong says. “We’d try to infer the function of brain regions from the clinical changes that resulted from lesions. Now we’re learning, almost inadvertently in some cases, by stimulating different parts of brain. It’s an interesting era."