Science Watch

When on a long plane flight, do you ever wonder how fatigue affects your pilot? So does the U.S. Air Force. In the June issue of Behavioral Neuroscience (Vol. 119, No. 3), military psychologists report on a study that revealed different patterns of brain activity that corresponded with individual differences in how tired pilots performed mentally.

The study launches a new approach for research into ways to reverse the cognitive effects of sleep deprivation and to improve job safety among pilots and others who work long, demanding hours.

At the Air Force Research Laboratory at Brooks City-Base in San Antonio, a Fatigue Countermeasures Team led by John Caldwell, PhD, compared how well fighter pilots and nonpilots performed certain tasks when snooze-deprived, and related that performance to brain activity via functional magnetic resonance imaging (fMRI). The results are sufficiently intriguing to warrant further study with larger samples and more rigorous controls, say the researchers.

It seems that sleepy people had sleepy brains, or, more specifically, less activity in specific regions of the cortex. The Texas team also confirmed and extended previous findings that while on average, sleep deprivation hammers thinking skills, everybody's different--and no one knows why. This perplexing phenomenon prompted the Air Force psychologists to take the problem into the lab.

"As is often the case, this initial study is not perfect, but it will motivate bigger studies designed to more directly test the hypotheses," says Sean P.A. Drummond, PhD, a psychologist with the Laboratory for Sleep & Behavioral Neuroscience at the University of California, San Diego, and the VA San Diego Healthcare System. "One of the holy grails of sleep deprivation research right now is the quest to find biological markers of individual vulnerability to sleep deprivation."

Snooze alarm

Predicting that vulnerability could help the military choose workers who can handle fatigue-inducing jobs. The commercial aviation community can take note because its pilots, aircrews and maintenance personnel work extremely demanding schedules. Also, says Caldwell, the research could benefit fire and rescue crews, emergency physicians, train engineers, truck drivers and others who routinely face intense work demands in terms of rotating shifts and prolonged periods with little or no sleep.

"This information could be used to help find the people best-suited to work in especially demanding occupations," says Caldwell, though he cautions that variations in vulnerability to fatigue should be factored with other predictors into a larger equation.

Researchers joining Caldwell came not only from the Air Force lab but the Medical University of South Carolina (MUSC) Center for Advanced Imaging Research in Charleston, the 49th Medical Group at Holloman Air Force base in New Mexico and the U.S. Air Force School of Aerospace Medicine at Brooks City-Base. The team ran the study in three phases.

Pilot study

During the first phase, at Holloman Air Force Base, the team gauged the F-117 flight-simulator performance of 10 active-duty Air Force pilots (average age 36 years) during 37 hours of continuous wakefulness to quantify the impact of fatigue and determine individual differences in their response to fatigue.

During the second phase, eight of the 10 pilots traveled to Charleston to have fMRI scans when they were rested. (Data on one pilot were excluded from analysis due to unusual deviation from the mean.) Thus, researchers learned how the baseline cortical activation of the pilots compared with that of non-pilots--both fatigue-resistant or fatigue-vulnerable as recorded in an earlier study published in the journal Sleep (Vol. 28, No. 1, pages 55-67) by Caldwell's co-author Qiwen Mu, PhD, of the South Carolina lab, and colleagues. After 30 hours of sleep deprivation, that study's participants were "fatigue resistant" if their reaction times were shorter and fatigue didn't change their error rate. When sleepy, "fatigue vulnerable" people had significantly longer reaction times and made significantly more mistakes.

The imaging scans showed which parts of the brain had more blood flow during the various cognitive tasks. Blood flow, measured in "activated voxels" (a voxel, short for volume pixel, represents a tiny 3-D "box" in the brain), is thought to mainly reflect local synaptic activity--that neurons are networking more.

During the third phase, researchers correlated the pilots' brain-imaging data with actual flight-performance data obtained in a previous Air Force study. This phase showed the degree to which the researchers could use differences in brain-activity levels to possibly predict individual differences in fatigue vulnerability.

As predicted, the researchers found significant variation in how pilots performed: One of the 10 pilots was virtually unaffected, whereas others suffered average performance drop-offs from 11 to 60 percent and peak drop-offs as high as 135 percent. More newsworthy were the positive relationships between fatigue resistance in terms of stable flight performance and significantly more global brain activation during the memory task.

"Thus, it appears that the greater amount of baseline cortical activation, the less performance will be affected by fatigue during a period of sleep deprivation," write the authors.

The scientists don't yet know why individual differences in performance are associated with different patterns of brain activation; more studies are needed to assess whether factors including but not limited to cardiovascular health, activity levels, education and so on play a role.

"These results show that there may be a biomarker present even when people are rested," explains co-author Mark George, MD, a distinguished professor of psychiatry, radiology and neurology at MUSC and director of its Center for Advanced Imaging Research and Brain Stimulation Laboratory. "Important future work would be to try and understand why we find these at-rest differences. The answer would have important ramifications in developing new methods for temporarily reversing sleep-deprivation cognitive effects."

Wake-up call

Drummond says he would have predicted the opposite result--that a less active cortex would have led to greater resiliency to sleep deprivation--in part because the prefrontal cortex slumbers so deeply that it may benefit the most from beauty sleep.

He cites evidence that a cortex that's more "on" during the day has to turn off more at night, complicating the Air Force finding that a more on-duty cortex fought fatigue more firmly. In what Drummond calls a cognitive reserve model, a lower-idling brain might have more reserves to summon under the stress of sleeplessness. Caldwell's finding, he adds, suggests instead that some brains are real workhorses--at work or at rest, they labor the hardest.

More research can straighten this out and trace the underlying mechanism, say experts. Caldwell hopes to replicate the findings on a larger group of pilots using flight simulators to assess the validity of his preliminary results. And he speculates that it may one day be possible to look at someone's baseline brain activity to gauge their hardiness when they have to stay awake.

Drummond notes methodological limitations. As the authors are first to point out, he says, the sample is quite small; he also wonders whether the scans were compromised due to the fact that before the scans, the pilots were partially sleep deprived, having slept fewer than seven hours the night before (one less than usual) and that caffeine intake was not controlled. In some but not all studies, sleep deprivation has been shown to increase activation levels--as does caffeine.

Finally, he views the volume of brain activation as a measurement of limited utility and says, "A more powerful strategy would have been to correlate performance with the magnitude of the brain response in various regions."

Meanwhile, Drummond will continue to study brain activation in those at rest and sleep deprived--helped along by an explosion in brain-imaging techniques. Indeed, new techniques emerge almost monthly, George notes. They are being translated into methods for diagnosing diseases, and also predicting who responds to which therapies."

Rachel Adelson is a science writer in Raleigh, N.C.