Pupil noise is a discriminator between narcoleptics and controls

The pupil light reflex has a long history of being able to indicate states of mental arousal, ranging from sleepiness to concentrated cognitive effort. Such mental states have usually been inferred from pupil diameter or pupil area movements relative to some reference; sleepiness, for example, is characterized by a smaller than average pupil while mental effort brings on a slightly larger pupil. But all pupil movements and associated states of arousal are accompanied by a persistent random pupil diameter motion which has previously been attributed to neurological noise, the noise apparently arising in the neurological controller of the pupil reflex control system. The authors' experiments and signal processing methods show that the amplitude of this pupil noise is an indicator of the sleeping disorder narcolepsy. Narcoleptics are found to have diminished pupil noise amplitudes relative to control subjects. Pupil noise is estimated by statistical procedures which yield unbiased noise measures in the form of six-dimensional Gaussian vectors. Each subject is associated with a Gaussian vector which is optimally projected onto a scalar axis so as to maximize the mean square distance between the narcoleptic and control samples. The Kullback-Leibler discrimination function is estimated and then evaluated for each projection as a means of discriminating narcoleptics from controls. The projected noise measures correctly classify 18 out of 20 subjects. The projected values also form the basis for supporting or rejecting a hypothesis of narcoleptic or control class membership. Parametric and nonparametric hypothesis tests suggest that, with probabilities close to one, narcoleptics and controls are distinguishable classes. To emphasize the importance of pupil noise as a diagnostic tool the authors present evidence from the neurophysiology literature indicating that Alzheimer's disease and narcolepsy have some of the same brainstem nuclei implicated. Further, Alzheimer patients and narcoleptics share some of the same disturbed sleep patterns.