Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity

The negative effects of sleep deprivation on alertness and cognitive perfor mance suggest decreases in brain activity and function, primarily in the th alamus, a subcortical structure involved in alertness and attention, and in the prefrontal cortex, a region subserving alertness, attention, and highe r-order cognitive processes. To test this hypothesis, 17 normal subjects we re scanned for quantifiable brain activity changes during 85 h of sleep dep rivation using positron emission tomography (PET) and (18)Fluorine-2-deoxyg lucose ((18)FDG), a marker for regional cerebral metabolic rate for glucose (CM Rglu) and neuronal synaptic activity. Subjects were scanned prior to a nd at 24-h intervals during the sleep deprivation period, for a total of fo ur scans per subject. During each 30 min (18)FDG uptake, subjects performed a sleep deprivation-sensitive Serial Addition/Subtraction task. Polysomnog raphic monitoring confirmed that subjects were awake. Twenty-four hours of sleep deprivation, reported here, resulted in a significant decrease in glo bal CMRglu, and significant decreases in absolute regional CMRglu in severa l cortical and subcortical structures. No areas of the brain evidenced a si gnificant increase in absolute regional CMRglu. Significant decreases in re lative regional CMRglu, reflecting regional brain reductions greater than t he global decrease, occurred predominantly in the thalamus and prefrontal a nd posterior parietal cortices. Alertness and cognitive performance decline d in association with these brain deactivations. This study provides eviden ce that short-term sleep deprivation produces global decreases in brain act ivity, with larger reductions in activity in the distributed cortico-thalam ic network mediating attention and higher-order cognitive processes, and is complementary to studies demonstrating deactivation of these cortical regi ons during NREM and REM sleep.