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Biomedicine

Brain Boosters

Our reporter enters the new world of neuroenhancers.

It’s 2:00 p.m. on a Tuesday, and I’m feeling stupid and slightly grumpy. I have lingering jet lag because I took a trip to London last week and flew in last night from California. Now I’m sitting in the Brain Stimulation Unit of the National Institute of Neurological Disorders and Stroke in Bethesda, MD, with two electrodes affixed to my forehead. In a moment, a researcher in the lab of neurologist Eric Wassermann will activate a gizmo the size of a small clock radio, which will send an electric current through my frontal lobe, the part of the brain most associated with higher reasoning and emotion. For the next 40 minutes, the flow of electrons will create an electric field that lets neurons having to do with cognition and emotion fire more easily.

I’m here to investigate firsthand whether the latest brain gadgets and pills represent a new frontier in neuro­enhancement. Wassermann has already told me that his device will not turn me into an Einstein. He is hoping that in people with brain injuries or impairments from disease, it will stimulate the cognitive centers to function better than they would otherwise. “We are starting with testing healthy people to get a baseline for how the technique works,” he says.

Two days from now I’m planning to further tweak my mind by taking a brain-boost pill. Called Provigil, it differs from its predecessors in that it is believed to home in on a section of the brain that helps govern alertness and memory. The pill is manufactured by ­Cephalon of Frazer, PA, and its active ingredient is called modafinil. The drug’s targeted delivery is supposed to prevent the side effects of stimulants that diffuse throughout the brain and rev up everything. Provigil has been approved by the U.S. Food and Drug Administration for people who have excessive sleepiness associated with narcolepsy or otherwise disrupted sleep patterns–for example, from switching between shifts at work. In 2006, 2.6 million ­Provigil prescriptions were written. More than half of those were reportedly for off-label uses such as treating attention deficit disorder and depression.

In the Brain Stimulation Unit, a medical student turns on the juice under the watchful eye of Michael ­Koenigs, the postdoc running the experiment. I feel a slight tingle and an itch on my scalp as the current rises to 2.5 milliamps: a small amount, but enough to give a jolt. A couple of minutes later I have a metallic taste in my mouth. Koenigs warned me this might happen. Hundreds of people have been tested, and this is one of the few side effects they’ve reported.

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In previous experiments on healthy people, Wassermann and others found that this procedure, called transcranial direct-current polarization, improved motor and cognitive performance. In one test, a direct current applied to the left frontal lobe boosted, by 20 percent, a person’s ability to name as many words beginning with a certain letter as possible in 90 seconds. Wassermann’s team is now testing electric fields with different charges against each other and against a sham, comparing subjects’ responses through tests that measure cognition, memory, and emotions.

Direct current applied to the scalp polarizes underlying brain tissue, creating either a positive or a negative charge near the electrode. In vitro studies have shown that a weak current can substantially change the firing rate of neurons–with an increase or decrease in firing rate that depends on the orientation of the electric field. Evidence suggests that increases in firing enhance local brain function and decreases do the opposite.

Zapping brains is not new. In the 1960s, low-level direct current was used to treat mental disorders, but investigators became more interested in chemical treatments until recently, when neuroscientists and clinicians began looking for targeted brain boosters with fewer side effects than pills. Wassermann thinks that one day we will be able to buy a tiny device that can be inserted into a hat or attached to a headband and turned on when we need a brain boost.

My Brain, Altered
I feel a slight uptick, like a medium hit of caffeine; it gently lifts the fog of my fatigue, though I don’t feel any smarter. I settle down to take some tests of cognition and emotion. Most telling is a gambling game that pre­sents four virtual decks of facedown cards on a computer screen; when I click on them, cards turn over, and I either win money or lose it, depending on the card. A ticker measures my winnings at the top of the screen. At first the cards seem random, but then patterns develop: I need to figure out which stacks will yield more gains than losses, and vice versa. After a few minutes, my initial mild boost dissipates. I lose at the gambling game, though not by much. The next morning I return after a good night’s sleep. Taking the gambling test sans stimulation, I win a modest amount of virtual cash.

Later that second day I participate in a third experiment. Instead of running a negative current through the electrodes attached to my forehead, as he did the first time, Koenigs applies a positive current. The effect on my frontal lobe causes a noticeable sense of relaxation and a drop-off in motivation as I play the gambling game. Oddly enough, I win big anyway. I also experience a strange sensation when I begin speaking to the researchers: I’m starting sentences and then losing my motivation to finish them. Koenigs says this is exactly what his experiment is trying to show: that performance is affected differently by different currents. I suspect my results have more to do with yesterday’s exhaustion versus today’s well-restedness, but the electricity has noticeably messed with my mind.

The day after that, I’m in New York City in the office of Steven Lamm, a physician who advocates the prescription of Provigil for patients with sleep disorders, persistent fatigue, or jet lag. “I would like to prescribe it more than I do,” he says, “but because it has only been approved for severe sleep disorders, insurance doesn’t cover the cost of the drug for many of my patients.” Lamm has used Provigil himself when he is jet-lagged or short on sleep and needs to be sharp. “It is unhealthy to not get enough sleep,” he tells me, “but sometimes it can’t be helped.” Lamm checks my blood pressure and takes a history, tells me about the drug, and scribbles out a prescription for five 200-milligram tabs.

Modafinil has been extensively studied as a treatment for sleep disorders, but data on its capacity for cognitive enhancement is thin. In Cambridge, England, researchers saw a spike in the short-term memory and planning ability of male volunteers who took the drug. Other researchers saw bone-tired subjects who took Provigil stay alert while using helicopter simulators; tests have also indicated that the drug can improve planning and the ability to remember long strings of numbers.

I swallow a pill at around 2:00 p.m., roughly the same time of day I was first tested in Eric Wassermann’s lab. I’m walking down Fifth Avenue in the bright spring sunshine and feel nothing. I get a cell-phone call and start talking, feeling my usual afternoon dopiness. Later I board a flight back home to San Francisco, and about three hours after popping the pill, I fall asleep.

In San Francisco, I try Provigil again at 8:00 a.m., along with my usual cup of coffee. This time, after 15 or 20 minutes, I feel an alertness that caffeine alone doesn’t usually give me; the feeling plateaus over the next three hours and resolves into a low-key but constant “up” sensation. I plunge into work and feel highly efficient and bright. For a little while, the sensation is almost too much, as if my brain has been set to fast-forward and can’t be turned off.

That morning, I talk to Jeffry Vaught, the research and development chief at Cephalon. He tells me that the pill is a mild stimulant and does not prevent sleep if people desire it. “For people with narcolepsy,” he says, “the impact is not mild; it’s life changing.” Vaught says the mechanism behind Provigil’s effect is not well understood, but scientists know what part of the brain it involves. “It’s a pathway involved with wakefulness, with waking you up and keeping you attentive,” Vaught says. “This pathway is activated by modafinil.” Major stimulants such as caffeine and amphetamines act on this part of the brain, too, but they also activate other regions, causing side effects such as jitters, loss of appetite, and that edgy feeling.

As the day wears on, my steady up-ness begins to get annoying. I’m calm, but I realize that when I write without the drug, I experience an intricate pattern of short ups interspersed with mild downs, during which I rest my brain. I’m not used to this uniform pharmaceutical lift.

Before long we might be drinking beverages laced with modafinil and other mild stimulants that have fewer side effects than coffee. It’s likely that we’ll also be slipping zappers onto the brims of our hats and flipping them on when we get spacey. But neither of these brain boosters is close to helping me, say, understand advanced quantum mechanics or write a symphony like Mozart. I’ll have to muddle along being me for a bit longer.

David Ewing Duncan is a Technology Review contributing editor. His next book is Experimental Man: A Molecular Autobiography.

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