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Sniffing May Prepare Brain For Smelling STANFORD, CA -- March 18, 1998 -- The act of sniffing may be a wake-up call, alerting the brain to the imminent arrival of a smell, Stanford researchers propose. Processing of either sniff or smell signals -- airrushing up the nose, or odourant molecules latching onto nerve cells -- could be defective in the many people who lose their ability to smell, the team's new findings suggest. Every year in the United States, more than 200,000 people visit their physicians complaining of problems with smell. Smell dysfunction affects most people with PARKINSON'S or Alzheimer's disease, often emerging as an early symptom of those conditions. "We have discovered what appear to be two different aspects of olfactory processing," said John Gabrieli, assistant professor of psychology at Stanford. "One is the exploratory phase -- the sniffing. And the second is the evaluative one -- the smelling. "In humans, it hadn't been thought that you could separate the two out." Gabrieli is the senior author of the new research report, published in tomorrow’s issue of Nature. The lead author is Noam Sobel, a graduate student in Stanford's neuroscience program. Sobel, Gabrieli and their colleagues defined the sniff and smell phases as separate by looking at images of brain activity. When human volunteers in their study sniffed in the absence of any odour, brain images showed that an area called the piriform cortex was most active. But when the volunteers actually detected a smell, other areas in the frontal lobe were most active. The images showed some overlap between the brain areas activated. This suggests that the sniff response primes the brain to receive the smell signal. "Obviously your nose is open all the time, but conceptually the sniff response can be compared to opening your eyes," he said. "One could view it as a warning that a smell is coming, as an attentional mechanism. "Some people laugh at me for explaining it this way, but I use the example of going into a public bathroom. It's only with your first sniff that the odour really hits you. If you don't do the intentional exploration, you don't notice the odour content." It is not, the researchers found, the movement of nose muscles that primes the brain. Instead, it is air rushing up the nose. An attempted sniff that is frustrated by blocked nostrils does not work, but air blown up the nostrils in the absence of a sniff does work -- so even a good gust of wind should do the trick. Partially blocked nostrils, which require the application of greater sniffing power for less total air movement, result in less activation in the piriform cortex, the team observed. The researchers measured brain activity with a procedure called functional magnetic resonance imaging, or fMRI. This detects increases in the levels of oxygen delivered to active nerve cells. The volunteers were awake and responding to instructions, so numerous areas of the brain were active during the study. But under different test conditions, only the sniffing and smelling activities changed. By subtracting brain activity in the absence of sniffing from brain activity with sniffing, the researchers found the specific signal they were looking for. Scientific understanding of olfaction is still primitive, Gabrieli said, but researchers can immediately use this new knowledge to figure out why people lose their sense of smell. "It wasn't evident before that there were these two phases of olfactory processing," Gabrieli said. "Now we can ask which one goes wrong in disease." Judith Richards [log in to unmask]