A Healing Spark

Years of painstaking observation and careful study is what typically leads to scientific breakthroughs, but serendipity can also play an important role, as Dr. Andres Lozano recently discovered.

Not long ago, the U of T neurosurgeon was implanting an electrode into the brain of an obese patient in an experimental procedure designed to suppress the man’s appetite. When Lozano switched on the electrode to deliver tiny electrical pulses, the patient (who was awake for the surgery) suddenly remembered a visit to a park with his girlfriend 30 years earlier. When Lozano increased the current, the patient was able to recall vivid details, such as the type of dress that his girlfriend was wearing and the warmth of the sun that day. When the current was off, the memory faded. “We were flabbergasted,” says Lozano. “We could unlock and lock memories by turning the current on and off.”

Lozano, who holds a Canada Research Chair in Neuroscience and is a professor of surgery at U of T, wondered if he had stumbled on a potential new treatment for people with memory problems. He conducted further tests on the patient and found that the man’s ability to remember pairs of words tripled when the electrode was turned on. Recently, as part of a research study, Lozano performed the identical procedure on six patients with mild Alzheimer’s. Results so far are promising. “We’re seeing some positive changes in their brain activity, their memory and their cognitive ability,” he says. “And so far, the procedure seems quite safe.”

To perform the surgery, Lozano drills a nickel-sized hole through the patient’s anesthetized scalp. He then inserts a millimetre-wide electrode into the brain, runs a wire underneath the scalp and neck and connects it to a battery a little smaller than a hockey puck, which he implants near the patient’s collarbone. The subject remains awake during the surgery to help ensure that Lozano places the electrode correctly (but is under general anesthetic while the wire and battery are implanted). Following the operation, the patient, by pressing the buttons on a remote control, can turn on the current and adjust the level to alter the intensity of the treatment.

Scientists began experimenting with deep brain stimulation on animals in the 1950s. The first humans underwent tests a decade later. Since then, as more detailed maps of the brain have emerged, surgeons have used the technique to control phantom limb pain and the tremors associated with Parkinson’s disease. Lozano pioneered the surgery for treatment-resistant depression and Alzheimer’s, and is now testing it for Parkinson’s patients who have difficulty with balance and walking.

How deep brain stimulation works is not well understood. Scientists believe that, depending on the precise position of the electrode, the current either stimulates or inhibits neuronal activity. In the case of Parkinson’s tremors, it’s thought that the electrical pulses inhibit nearby neurons from firing excessively. With depression, underperforming neurons get a boost. In both cases, the surgeon must position the electrode in exactly the right spot. “It’s like real estate,” says Lozano. “The three most important things are location, location, location.”

Ultimately, Lozano’s research has two aims: to develop novel therapies for patients with difficult-to-treat neurological and psychiatric conditions; and to better understand how deep brain stimulation works at the cellular and molecular level. The research will also yield more information about the role that neurons play in different regions of the brain. “It’s like exploring space,” he says. “We’re interrogating the brain for the first time to find out what it does.”

Five to 10 years from now, Lozano predicts doctors will use deep brain stimulation to treat other diseases, such as Tourette’s syndrome, obsessive-compulsive disorder and epilepsy. Newer electrodes will be able to detect abnormal brain activity and then automatically deliver an electric pulse – to stave off an epileptic seizure, for example. By 2040, tiny computer chips might download information directly to brain cells (encyclopedic knowledge, anyone?), though such a possibility raises serious ethical issues. “Right now we’re talking about treating people who have a disease. But you could imagine boosting the function of someone who is normal,” says Lozano. “Already I’ve had people writing to me to volunteer.”