Hippus pupil11/3/2022 Pupil diameter was recorded with an infrared eye-tracker (Eyelink 1000, SR Research, Mississauga, Ontario, Canada) running in binocular mode at 500 Hz. 24 – 26 By occluding either the left or right eye to differentially activate each cortical hemisphere, and by extension the PNS or SNS, they saw slight differences in pupil dilation based on which eye was occluded, but their study lacked sufficient power to detect a difference in hippus activity. 23 attempted to tease out the role of the PNS and SNS in hippus by exploiting both the modest asymmetry in monocular visual field projection and inherent cortical lateralization of the autonomic nervous system. 18, 19 Some have suggested that hippus is a function of SNS tone alone, 20 while others have suggested it is driven by the PNS input, 17, 21 despite dissonance between accommodative microfluctuations and hippus. Additionally, hippus is partially correlated with respiratory 17 and cardiac activity. 10, 14 – 16 However, the origin of hippus is likely in the central nervous system, rather than local to the eye, because hippus movements are bilaterally consensual. 8, 13 Some have hypothesized that as pupil diameter is determined from the relative input of the SNS and PNS, hippus is likely due to feedback or noise from this continuous neurologic antagonism. The role of the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) input to the iris as a determinant of overall pupil size has been well described 10 – 12 however, the mechanism of hippus remains elusive. This suggests that hippus originates from central PNS activity, and not from SNS activity, or oscillations in the balance between PNS and SNS at the pupil. Pupillary hippus can be extinguished by antagonizing the PNS, whereas agonizing the SNS dilates the pupil without affecting hippus. Hippus magnitude (treatment eye relative to control eye) decreased in the TL (−72.8 ± 4.7%, P < 0.0001) and TD (−71.3 ± 2.6%, P < 0.0001) groups, but did not change in the PL (+5.4 ± 13.7%, P = 0.173) group, despite PL pupils dilating to a proportion similar to TD. Pupillary hippus with a distinct dominant frequency was present in all measures at baseline (mean: 0.62 Hz, SD: 0.213 Hz), and that frequency did not change in any group ( P = 0.971). Hippus, analyzed in both time and frequency domains, was compared between eyes and cohorts. Measures were taken at baseline, then every 5 minutes for 40 minutes. Bilateral measures of pupil size and dynamics were made over 2.6 seconds using an infrared eye-tracker sampling at 500 Hz. Each subject received one drop to the randomly determined treatment eye, while the other eye served as control. We used a paired-eye control study design with three cohorts receiving either 1.0% tropicamide (PNS antagonist) in light (TL), 1.0% tropicamide in dark (TD), or 10% phenylephrine (SNS) in light (PL), n = 12 in each. The purpose of this study was to determine the relative roles of the sympathetic (SNS) and parasympathetic nervous system (PNS) in pupillary hippus.
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