Objective: Problem sleepiness, involuntarily falling asleep during waking hours, is a major U.S. public health problem that is manifested as a result of sleep deprivation as well as intrinsic sleep disorders. A 1999 AHCPR evidentiary review found substantial deficits in the inconvenient, intrusive and costly "gold standard" polygraphic measures used to evaluate problem sleepiness. Furthermore, health care professionals tend to ignore problem sleepiness complaints, or provide simplistic sleep-related advice because of inadequate ways for objectively measuring sleepiness.
Pupillometry is a convenient, easily repeatable clinical technique for measuring pupil constriction and oscillation, signs that have been observed to occur concurrent with behavioral indicators of sleepiness. While used clinically since the 1970's, little scientific evidence exists in published literature about the consistency (reproducibility) and accuracy (validity) of this physiologic technique as a measure of sleepiness. This presentation describes a program of research consisting of three studies that have been undertaken to establish the scientific basis for monitoring pupil size and oscillation during a 15 minute test as a measure of sleepiness.
Reproducibility study. Pupil size was measured at the same time of the morning with infrared video cameras at 60 Hz for 15 minutes in a quiet, dark environment [the Alertness Level Test (ALT)] with 12 normal subjects who had no clinical evidence of a sleep disorder and maintained their usual daytime wake-nighttime sleep pattern for 5 consecutive days. Repeated measures ANOVA procedures found no significant difference between days among the subjects for the dark adapted pupil diameter [F (4)=1.07, p .38], and for the pupil unrest index (PUI), a measure of the average amount of pupil oscillation over time [F (4)=1.95, p .12].
Sensitivity to ultradian sleepiness study. The ALT was conducted with 11 normal subjects every 2 hours for 4 times on one day to determine if this test demonstrated significant pupil constriction and oscillation in the afternoon when an increase in sleepiness is expected and demonstrated on polygrahic daytime nap studies. Linear regression of pupil diameter data for the 4 time periods demonstrated that the estimated slope of the line for the 2 PM period was significantly greater than each of the other 3 time periods (10 AM - p .005, 12N - p .005, 4 PM - p .02). Repeated measures ANOVA with post hoc Scheffe testing revealed the amount of pupil oscillation (PUI) was significantly greater at 2 PM compared to the other 3 time periods, and therefore, sensitive to the usual dip in day time alertness.
Validity of the ALT study. As people become sleepy, the size of their pupils decreases; at sleep onset the pupils become severely constricted and quiescent. The ALT was conducted with 16 controls, 16 sleep apnea and 16 narcoleptic subjects (known groups design) to determine if the amount of EEG theta activity increased (an objective indication of increasing sleepiness in awake individuals) as pupil size decreased (Stage 1 "awake"=95% of maximum diameter to Stage 4 "sleepy"=65 -74% of maximum diameter). FFT and power spectral analyses were used to process EEG data that were then aggregated for each subject according to pupil stage. ANOVA procedures with post hoc least significant difference testing revealed that there were significant increases in the amount of theta activity as pupil stage increased both within and between groups, providing evidence that a proportional change in pupil size during the ALT is an accurate estimate of sleepiness.
Conclusion: This program of research supports the reliability, sensitivity and validity of pupil constriction and oscillation as signs of increasing sleepiness. Further comprehensive testing is warranted given the costs and inconveniences of polygraphic measures. Recent technologic advances and miniaturization in desktop pupillometry means that it could be possible to objectively measure sleepiness with people wherever there is a quiet, dark environment.
Research supported by NIH, R15 NR04030 and Mr. J. A. Piscopo.
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