scholarly journals Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD

2018 ◽  
Vol 8 (11) ◽  
pp. 108 ◽  
Author(s):  
Georgina Lynch

With recent advances in technology, there has been growing interest in use of eye-tracking and pupillometry to assess the visual pathway in autism spectrum disorder (ASD). Within emerging literature, an atypical pupillary light reflex (PLR) has been documented, holding potential for use as a clinical screening biomarker for ASD. This review outlines dominant theories of neuropathology associated with ASD and integrates underlying neuroscience associated with the atypical PLR through a reciprocal model of brainstem involvement and cortical underconnectivity. This review draws from animal models of ASD demonstrating disruption of cranial motor nuclei and brain imaging studies examining arousal and the influence of the locus coeruleus norepinephrine (LC-NE) system on the pupillary response. Pupillometry methods are explained in relation to existing data examining the PLR in ASD and pupillary parameters of constriction latency and tonic pupil diameter as key parameters for investigation. This focused review provides preliminary data toward future work developing pupillometry metrics and offers direction for studies aimed at rigorous study replication using pupillometry with the ASD population. Experimental conditions and testing protocol for capturing pupil parameters with this clinical population are discussed to promote clinical research and translational application.

2012 ◽  
Vol 43 (8) ◽  
pp. 1910-1925 ◽  
Author(s):  
Chathuri Daluwatte ◽  
Judith H. Miles ◽  
Shawn E. Christ ◽  
David Q. Beversdorf ◽  
T. Nicole Takahashi ◽  
...  

2016 ◽  
Author(s):  
◽  
Dinalankara M. R. Dinalankara

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Pupillary light reflex (PLR) is a phenomenon wherein the pupil size changes according to retina illumination. PLR of adults and children has been investigated in various studies. However, its significance in the medical care of young children and infants has been limited due to the lack of reliable instrumentation. Traditional PLR devices need to restrain subject or have to be worn on the head, which is not suitable for young children. A remote PLR measuring device was developed which allows the subject to sit far from the device during the PLR test. The device can capture high resolution images at a high sample rate similar to what can be found in a desktop system, but without the need for a restraint. The device follows the subject by tracking their eye movements during the PLR test. The device has been used to test PLR in typical developing (TD) children and children with autism spectrum disorders (ASDs), who were between ages of two to six years old. It was found that PLR latency in children with ASDs was longer than in typical developing children. The PLR constriction of the ASD subjects was slightly smaller than the TD subjects, but that difference was not statistically significant in our test. Moreover, the base pupil radius increased and latency decreased with age in the TD children but not in the ASD group. We found that PLR parameters are associated with autonomic nervous system (ANS) dysfunction. TD children with abnormal sweating issues showed a larger PLR constriction and smaller base pupil radius. We found that children with ASD did not show such differences. However, constriction time is negatively correlated with the normalized high frequency component of heart rate variability power spectrum in the ASD group, but not in the TD group. Nine TD children and eight ASD children were tested again 1-1.5 years from their first test date. The PLR parameter differences between the first and second tests were calculated, and we found that latency difference was negatively correlated to base pupil radius difference. Moreover, constriction difference was found to be positively correlated to the base pupil radius difference in TD children, but not in the ASD group. Remote PLR device camera setup was changed to capture the test subject's motion by a one camera while the other camera captures a high resolution pupil image. Because the two cameras are off axis, 3D location of the eye position is directly calculated using stereo vision base method, which helped to remove the need of physical measurement. The entire space occupied by the new rPLR device is about 50% of the previous device.


2000 ◽  
Vol 84 (2) ◽  
pp. 964-974 ◽  
Author(s):  
Milton Pong ◽  
Albert F. Fuchs

Anatomical and physiological data have implicated the pretectal olivary nucleus (PON) as the midbrain relay for the pupillary light reflex in a variety of species. To determine the nature of the discharge of pretectal light reflex relay neurons, we recorded their activity in monkeys that were fixating a stationary spot while a full-field random-dot stimulus was flashed on for 1 s. Based on their discharge patterns, neurons in or near the PON came in two varieties. The most prevalent neuron discharged a burst of spikes 56 ms (on average) after the light came on followed by a sustained rate for the duration of the stimulus (burst-sustained neurons). When the light went off, nearly all neurons (33/34) ceased firing, and then all the neurons with a resting response in the dark ( n = 15) resumed firing. Both the firing rate within the burst and the sustained discharge rate increased with log light intensity and the latency of the burst decreased. The burst and cessation of firing were better aligned with the stimulus occurrence than with the onset of pupillary constriction or dilation. Taken together, these data suggest that burst-sustained neurons respond to the visual stimulus eliciting the pupillary change rather than dictating the metrics of the subsequent pupillary response. Electrical stimulation at the site of four of five burst-sustained neurons elicited pupillary constriction at low stimulus strengths after a latency of ∼100 ms. When the electrode was moved 250 μm away from the burst-sustained neuron, the elicited response disappeared. Reconstructions of the locations of burst-sustained luminance neurons place them in the PON or its immediate vicinity. We suggest that PON burst-sustained neurons constitute the pretectal relay for the pupillary light reflex. A minority of our recorded pretectal neurons discharged a burst of spikes at both light onset and light offset. For most of these transient neurons, neither the burst rate nor the interburst rate was significantly related to light intensity. We conclude that these neurons are not involved in the light reflex but subserve some other pretectal function.


2003 ◽  
Vol 89 (6) ◽  
pp. 3179-3189 ◽  
Author(s):  
Robert J. Clarke ◽  
Hongyu Zhang ◽  
Paul D. R. Gamlin

This study investigated the static and dynamic characteristics of the pupillary light reflex (PLR) in the alert rhesus monkey. Temporal characteristics of the PLR were investigated with Maxwellian viewing during sinusoidal changes in illumination of a 36° stimulus in both monkeys and humans. Bode plots of the PLR response were fitted by a linear model composed of a delay combined with a cascaded first- and second-order filter. The Bode magnitude plots conformed to this model with a sharp roll-off above 1.3 Hz for the human PLR and 1.9 Hz for the monkey PLR. Bode phase angle plots were fitted by this model with a delay of 280 ms for humans and 160 ms for monkeys. To investigate the influence of the sympathetic innervation of the iris on steady-state pupil diameter, dynamics of pupillary responses, and the latency of the PLR, we blocked this innervation pharmacologically with a selective alpha-1 adrenoreceptor antagonist. Although there was a resultant miosis (decrease in pupil diameter) from the relaxation of the pupil dilator muscle, no other measures of the PLR, including the dynamics and latency, were significantly affected by this treatment. We examined the pupillary responses evoked by visual stimuli presented either binocularly or monocularly at various locations on a 80 × 60° tangent screen. These pupillomotor fields revealed that, as has been reported for humans, stimuli at the fovea and surrounding macular region of monkeys produce substantially larger pupillary responses than more peripheral stimuli and that binocular responses are substantially greater than can be accounted for by the linear summation of binocular retinal illuminance. In conclusion, we found that the spatial characteristics of the PLR of the rhesus monkey are very similar, in all important aspects, to those reported for humans and that the temporal responses of the PLR are comparable between the two species. The rhesus monkey thus provides an excellent model for experimental studies of the neural control of the pupil.


2017 ◽  
Vol 10 (5) ◽  
pp. 829-838 ◽  
Author(s):  
Dinalankara M. R. Dinalankara ◽  
Judith H. Miles ◽  
T. Nicole Takahashi ◽  
Gang Yao

2019 ◽  
Vol 7 (3_suppl) ◽  
pp. 2325967119S0015
Author(s):  
Olivia E. Podolak ◽  
Nabin Joshi ◽  
Kenneth Ciuffreda ◽  
Fairuz Mohamed ◽  
Shelly Sharma ◽  
...  

Background: Visual deficits and autonomic dysfunction have been well recognized following pediatric concussion. Testing of the pupillary light reflex (PLR) is a simple, non-invasive, and objective approach to examine the autonomic nervous system by accessing the brain pathways. The aim of this study was to objectively evaluate adolescent pupillary responses to a light stimulus after a physician-diagnosed concussion and compare them to baseline responses. Methods: In this prospective cohort study, PLR was assessed in 135 adolescent athletes (ages 14-18) during their sport pre-season. All of the athletes were not recovering from a concussion at the time of their baseline assessment. Within this cohort, seven athletes (ages 14-17) sustained a concussion during their sport season and had longitudinal post-injury assessments of PLR through their recovery. The PLR was obtained in response to a brief step-input (0.8 seconds) white light stimulus using a hand-held pupillometer (stimulus recording duration= 5 seconds, light intensity= 150 lux). Pre-set and automated device-generated parameters used for analysis include the minimum and maximum pupil diameter, response amplitude and latency, mean constriction and dilation velocities and the maximum constriction velocity of the eye in response to a light stimulus. During each assessment, three monocular trials were performed in each eye alternatively, and the responses for each eye were subsequently averaged. Results: Six out of the seven concussed adolescents showed response enhancement of about 20% (IQR 11-33%). Enhancement was noted in the steady state diameter with a mean of 24% (median 18%), minimum pupil diameter mean of 17% (median 11%) and maximum constriction velocity mean of 28% (median 33%) following concussion, which decreased during the recovery process (days to weeks post-injury) to pre-injury or below initial pre-injury baseline measurements. Pupillary responsivity was found to be significantly enhanced after concussion compared to baseline measurements, waning over time. Maximum constriction velocity better highlighted the enhancement compared to the baseline pupil diameter. Conclusions/Significance: Pupil responsivity was found to be significantly enhanced after concussion compared to baseline measurements which waned over time during recovery. Assessment of dynamic PLR responses has potential utility as an objective biomarker to aid in concussion diagnosis on the sidelines or in the office, allowing physicians to quantify function (and dysfunction) of the autonomic nervous system under parasympathetic and sympathetic control after concussion.


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