The Year in Science: Neuroscience

Sunday, January 08, 2006

Brain Scans Show How Placebos Stop Pain

Need something to dull those nagging aches and pains? Try a placebo.

In a report last August a research team at the University of Michigan measured placebo-related brain chemistry for the first time, moving the effect beyond the realm of subjective observation.

In the study, led by neuroscientist Jon-Kar Zubieta, researchers injected a salt solution into the jaws of 14 men to produce an ache. Each was given a placebo—an injection said to be an experimental pain medication. Nine of the men said the pain subsided.

PET scans turned up differences in brain activity. Those who reported pain relief after taking the placebo showed increased activity in parts of the brain associated with modulating pain. A radioactive tracer also revealed that binding occurred at receptors for naturally occurring pain-fighting endorphins.

"If somebody believes something will work," says Zubieta, "that positive expectation by itself, through different connections in the brain, activates mechanisms that suppress pain. We saw a linear relationship between how people reported pain and how their brains released opioids."

Understanding the effect would help researchers conduct better drug trials. "In trials, you want to minimize the placebo effect so you can see what the actual drug is doing," says Zubieta, who hopes the research can produce better ways of dealing with pain.  —David Epstein

Laser Lights Up Fruit-Fly Brains

Researchers used to employ a crude technique to figure out what particular neurons do: They zapped them with an electrode and watched which muscles twitched and how the person reacted. Now a new generation of scientists is using light to study the activity of neurons—including those previously inaccessible—without damaging nearby cells. A breakthrough method, described in an April report by Gero Miesenböck of Yale University, can induce behavior with a beam of light.

In the experiment, certain groups of neurons in flies are genetically engineered to have ion channels that can be opened by ATP, a chemical that allows the neurons to fire. Then a chemically modified version of ATP is injected into spaces between neurons. An ultraviolet laser frees the ATP, allowing it to rush into the ion channels of the modified neurons. "Think of it as a radio broadcast—the laser light is the transmitter, and each treated cell is a household that can pick up the signal," Miesenböck says. Depending on which neurons are modified, Miesenböck can make the fruit flies flap their wings or jump with the click of a button.

Although the intervention conjures up a puppeteer-like brain manipulation, Miesenböck doesn't view his innovation as a mind-control strategy. He intends to use it as a tool for learning more about brains. "If you had a hunch that a certain type of neuron might be important for a particular behavior," he says, "you could use this technique to see if that's the case—to find out whether activating those neurons elicits the behavior artificially."  —Elizabeth Svoboda

Brain Scientists Find Single Cells That Can Think

You may not be devoted to Halle Berry, but at least oneof your brain cells is. Christof Koch, a neuroscientist at Caltech, and Itzhak Fried, a neurosurgeon at the University of California at Los Angeles, revealed this spring that their research team had discovered individual brain cells that fire in response to particular people and places. A Bill Clinton neuron lights up at photos of the former president, but not for other ex-presidents,  males—or Hillary.

Such faithful neurons conflict with the conventional wisdom—a single cell is not supposed to know so much. With almost as many neurons in the neocortex as stars in the galaxy, there still aren't enough for every possible input, and the researchers suspect that brain cells get reserved only for important people—like Bart Simpson. Still, every idea may leave its own electrical trace. "Someday," says Koch, "we may be able to track the footprints of your thoughts." —Jessica Ruvinsky

Inhaled 'Cuddle' Hormone Promotes Trust

In the 1932 novel Brave New World, Aldous Huxley imagined that in 2500 a drug called soma would keep people mellow and content. A surprising report in June on a natural mood-altering substance did Huxley one better. When economist Michael Kosfeld and his colleagues at the University of Zurich administered nasal sprays containing the hormone oxytocin to a group of test subjects, they became substantially more willing to trust strangers with their money.

Kosfeld and his team set up a game in which one participant was cast as an "investor" and the other as a "trustee." Each investor was given currency and then received the following instructions: Any amount of money the investor transferred to the trustee would be tripled, but the trustee could return some, all, or none of the investor's money.

Investors who received a whiff of oxytocin before the experiment were much more likely to expect the trustee to share the windfall. "They would often transfer their whole endowment," Kosfeld says. Forty-five percent of test subjects who had received oxytocin beforehand gave their entire bankroll to the trustees, while only 21 percent of people in the control group did. Although scientists have long known that oxytocin, naturally produced by the pituitary gland, fosters attachment and bonding—it's called the cuddle hormone—this is the first evidence that it promotes trust.

Neuroscientists don't understand how oxytocin works, but Kosfeld has a hypothesis: "Many people are afraid of being betrayed, and that makes them cautious. Oxytocin may affect the extent of these negative evaluations, causing us to say, 'Oh, this won't be too bad.' " He scoffs at the suggestion that the compound could be used to subdue or motivate people against their will : "You can't put it in food or in your air-conditioning system."  A therapeutic nasal spray,  however, might help people suffering from psychological disorders, such as social phobias rooted in a lack of trust. —Elizabeth Svoboda

Why Some Stroke Victims Don't Make Smarter Decisions

Patients who have suffered stroke or head injuries often lose the ability to make smart choices. For instance, they will place repeated bets on a particular outcome, even when the odds of winning are obviously very low. In July a research team at Johns Hopkins University helped pinpoint why.

Previous studies suggested that the problems involve a brain area known as the orbital frontal cortex. To test how this area functions during decision making, the researchers presented the following task to normal rats and rats with damage: Figure out which of two odors led either to a sugary treat or to a bitter one. "If you saw a soda machine with foreign writing on it, you might push one button and get something really odd, so you wouldn't try that again," says Michael Saddoris, a member of the research team. "But if you came back the next day and got something you really liked, you'd push that button again and again." In the same way, the animals had to learn to use a smell cue to predict a particular outcome.

The next step was to reverse the cues for the sweet and bitter substances, then see how long it took for the rats to catch on. Those with defective brain circuitry had much more difficulty. Data from electrodes implanted into their brains showed that neurons in the impaired rats fired less often in the presence of odors. They weren't able to monitor the new circumstances and form new associations.

Understanding  how the orbital frontal cortex influences judgment may lead to therapies. "We're not at the level of using neuroprosthetics or implants to affect decision making yet, but it might be possible to get there," Saddoris says. —Elizabeth Svoboda  

Blinking Flips An Off Switch in Brain

You close your eyes about every five seconds without even noticing it. In July Davina Bristow, a graduate student at the Wellcome Department of Imaging Neuroscience at University College London, explained why that incessant blinking doesn't plunge you in and out of darkness. A simple experiment revealed that parts of the brain associated with visual awareness briefly shut off during a blink and fail to detect the blackness behind closed eyes.

Test subjects wearing blackout goggles had an optic cable inserted in their mouths to deliver a steady beam of light to the back of their retinas. Bristow then used a functional magnetic resonance imaging scanner, or fMRI, to monitor any brain activity triggered by blinking, independent of the effect of eyelid closure on light entering the eye. The fMRI scans revealed that blinking momentarily suppresses activity in the parts of the brain that process visual stimuli, preventing the intermittent sensation of darkness from reaching consciousness.

Bristow's blink experiment explores a general puzzle in neuroscience: How do our brains distinguish between events we have caused and external occurrences? Although blink suppression was a well-known cognitive phenomenon, just how it occurs in the brain was not, says psychologist David Burr of the University of Firenze in Italy. Other forms of cognitive suppression are even more familiar. One type allows a smooth streaming image to reach our brains even though our eyes jump around a lot. Flipping the suppression switch also explains an old childhood conundrum, says Burr. "If you tickle yourself, it doesn't worry you. If someone else tickles you, it does." —Anne Casselman

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