Characteristics of the Pupillary Light Reflex in the Alert Rhesus Monkey

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.

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.


2003 ◽  
Vol 89 (6) ◽  
pp. 3168-3178 ◽  
Author(s):  
Robert J. Clarke ◽  
Hongyu Zhang ◽  
Paul D. R. Gamlin

This study examined the response properties of luminance neurons found within the pretectal olivary nucleus (PON), which is the pretectal nucleus that mediates the primate pupillary light reflex. We recorded the activity of 121 single units in alert, behaving rhesus monkeys trained to fixate a back-projected laser spot while a luminance stimulus was presented. The change in the firing rate of luminance neurons was measured as a function of changes in the size, retinal illuminance, and position of the stimulus. We found that these neurons possessed large receptive fields, which were sufficiently distinct that they could be placed into three classes. Approximately 40% of the PON luminance neurons responded well to stimuli presented in either the contralateral or ipsilateral hemifield. These neurons were classified as “bilateral” neurons. In the primate, retinal projections to the pretectum and other retinorecipient nuclei are organized such that direct retinal input can only account for the contralateral hemifield responses of these neurons. Thus the representation of the ipsilateral hemifield in “bilateral” PON cells must result from input from a nonretinal source. Approximately 30% of PON neurons responded only to stimuli presented in the contralateral hemifield. These neurons were classified as “contralateral” neurons. Finally, approximately 30% of PON neurons responded to stimuli presented at or near the animal's fixation point. These neurons were classified as “macular” neurons. The mean firing rates of all classes of neurons increased with increases in stimulus size and luminance within their receptive fields. The thresholds and magnitude of these responses closely matched those that would be appropriate for mediating the pupillary light reflex. In summary, these results suggest that all three classes of PON neurons contribute to the behaviorally observed pupillomotor field characteristics in which stimuli at the macular produce substantially larger pupillary responses than more peripheral stimuli. The contributions of “bilateral” and “contralateral” cells account for pupillary responses evoked by peripheral changes in luminance, whereas the contributions of all three cell classes account for the larger pupillary responses evoked by stimuli in the central visual field.


2009 ◽  
Vol 1 (1) ◽  
pp. 19 ◽  
Author(s):  
Wolfgang H. Zangemeister ◽  
Thilo Gronow ◽  
Ulrich Grzyska

We examined effects of diabetes mellitus (DM) on the pupillary light reflex (PLR). Phasic pupillary response to a single light stimulus (200 ms) (pPLR) and to continuous sinusoidal stimuli with four different frequencies (0.1, 0.3, 0.7, 1.3Hz) (cPLR) were examined in 52 DM patients and 21 control subjects. We asked: does recording and frequency analysis of cPLR together with short time fourier [STFT] analysis of pPLR differentiate better between DM patients and normal subjects than pPLR only? Initial pupil diameter was significantly decreased in the DM group. For pPLR. maximal contraction velocity (Vmax), Vmax of redilation 1, reflex-amplitude and pPLR latency were significantly reduced in those patients who also showed signs of diabetic autonomic neuropathy (DNP). Tests of dynamic pupillary light reflex (cPLR) revealed that all DM patients had a significantly reduced gain at lower frequencies. Pupil phase lag was greater at 0.1 and 0.3Hz and smaller at 0.7 and 1.3 Hz in the DNP group (p<0.001). Comparison of single pPLR recordings of 5 DNP patients with 5 subjects using short time fast fourier (STFT) analysis revealed a characteristic change from low frequency content in healthy subjects to high frequency content in DNP patients. Significant changes in the PLR in DM can be found only when symptoms of autonomic neuropathy have been shown. Both sympathetic and the parasympathetic nervous systems are affected by diabetic autonomic neuropathy. Only recording of cPLR , together with STFT of pPLR can identify significant pathological deficits of pupillary control in single cases.


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.


2021 ◽  
pp. S513-S521
Author(s):  
A HAMRAKOVA ◽  
I ONDREJKA ◽  
N SEKANINOVA ◽  
L BONA OLEXOVA ◽  
Z VISNOVCOVA ◽  
...  

It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0±2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81±1.23 % vs. -30.32±1.31 %, p<0.05, left eye: -25.44±1.65 % vs. -30.35±0.98 %, p˂0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p˂0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.


2021 ◽  
Vol 8 ◽  
Author(s):  
Joji Kotani ◽  
Hiroyuki Nakao ◽  
Isamu Yamada ◽  
Atsushi Miyawaki ◽  
Naomi Mambo ◽  
...  

Background: Physicians currently measure the pupil diameter and the pupillary light reflex with visual observations using a ruler and a traditional penlight, leading to possibly inaccurate and subjective assessments. Although a mobile pupillometer has been developed and is available in clinical settings, this device can only assess one pupil at a time. Hence, an indirect pupillary light reflex, including those under irradiation to the opposite side of pupil, cannot be evaluated. Consequently, we have developed a new automatic mobile pupilometer, the Hitomiru®, with Hitomiru Co., Ltd. (Tokyo, Japan). This device is a two-glass type pupilometer with a video recording system. The pupil diameter and light reflex of both pupils can be measured simultaneously; therefore, both indirect and direct light reflexes can be assessed.Purpose: To evaluate the clinical ability of the Hitomiru® pupilometer to assess the pupil diameter and the pupillary light reflex of healthy volunteers and patients with intracranial lesions in an intensive care unit (ICU).Methods: Twenty-five healthy volunteers and five ICU patients with intracranial lesions on only the left side were assessed using the Hitomiru® pupilometer. The protocol was as follows: infrared light was applied to both pupils, followed by visible light to the right pupil, infrared light to both pupils, visible light to the left pupil, and then infrared light to both pupils. All the intervals were 2 s, and the dynamics of pupil diameters on both sides were continuously recorded.Results: The healthy adults had approximately 0.5 mm anisocoria, miosis was harder, and mydriasis was less with increased age. There were several differences in miosis rates, miosis times, and mydriasis rates between the healthy adults and the patients with intracranial lesions with both direct irradiation and indirect irradiation.Conclusions: The initial trial estimated and digitally recorded direct and indirect light reflexes, including rapidity of miosis after direct and indirect lights on, and mydriasis after direct and indirect lights off. The Hitomiru® pupilometer was a useful device to digitally record and investigate the relationship between pupil reflexes and intracranial diseases.


2000 ◽  
Vol 84 (2) ◽  
pp. 953-963 ◽  
Author(s):  
Milton Pong ◽  
Albert F. Fuchs

To investigate whether the simian light reflex is a reasonable model for the human light reflex, we elicited pupillary responses in three behaving rhesus macaques. We measured the change in pupillary area in response to brief (100 ms), intermediate (1 s), and long (3–5 s) light flashes delivered by light-emitting diodes while the monkey fixated a stationary target. Individual responses in the same monkey to either 100-ms or 1-s stimuli of the same light intensity were quite variable. Nevertheless, in response to the 100-ms stimulus, average pupillary constriction and peak constriction velocity increased and latency decreased linearly with the log of stimulus luminance. The minimum average constriction latency across monkeys for the brightest flash was 136 ms. A linear decrease of constriction latency with stimulus luminance also occurs in humans, but their latencies are ∼70 ms longer. In addition, peak constriction velocity was highly correlated with the decrease in pupillary area. Dilation metrics were not as well related to stimulus luminance as were constriction metrics. The latency from flash offset to the onset of dilation was relatively constant, averaging ∼480 ms. Peak dilation velocity was also correlated, but less well, with the increase in pupillary area. Constriction generally was greater and of longer duration for 1-s light pulses than for 100-ms pulses of equal luminance. The initial time courses of the responses to the two stimuli of different durations were identical until ∼150 ms after response onset. Human pupillary responses for long and short flashes also have identical initial time courses. For very long (3–5 s) and very bright constant-luminance stimuli, the simian pupil underwent oscillations at frequencies of 0.9–1.6 Hz. Similar oscillations, called hippus, occur in the human pupillary light reflex. Like humans, the monkeys also exhibited consensual and binocular pupillary responses. Except for response latency, the pupillary responses in the two primate species are otherwise quite similar. Therefore any knowledge we gain about the neuronal substrate of the simian light reflex can be expected to have considerable relevance when extrapolated to humans.


2020 ◽  
Vol 8 (4_suppl3) ◽  
pp. 2325967120S0027
Author(s):  
Olivia E. Podolak ◽  
Kristy B. Arbogast ◽  
Joshi B. Nabin ◽  
Kenneth Ciuffreda ◽  
Matthew Grady ◽  
...  

Background: Despite advancements, concussion diagnosis remains reliant on subjective symptom report and clinical assessments. Visual deficits and autonomic dysfunction have been described following concussion. Testing of the pupillary light reflex (PLR) is a simple, portable, non-invasive, and objective means of quantifying pupillary function. Purpose: The aim of this study was to objectively evaluate pupillary responses to a light stimulus in concussed adolescent athletes and to determine whether clinical assessments correlated with PLR responses after a diagnosed concussion when compared to pre-injury responses. Methods: In this prospective cohort study, PLR and clinical measures [PCSI and/or SCAT symptom scales, near point of convergence (NPC) and accommodation amplitude (AA) of both eyes] were assessed in 93 (45 female), non-concussed adolescent athletes (ages 14-18) during their pre-season. PLR was obtained in response to a brief white light stimulus using a hand-held pupillometer. During each assessment, three monocular trials were performed in each eye alternatively, with subsequent averaged responses for each eye. Seven athletes (ages 14-17) sustained a concussion and had post-injury assessments of PLR and clinical measures completed longitudinally through recovery. Results: All seven concussed athletes completed PLR and clinical assessments at least once post-injury (mean initial day of evaluation = 6 days post injury). Six out of the seven concussed athletes demonstrated an increase in steady state diameter of 24% (median 18%), minimum pupil diameter of 17% (median 11%) and a maximum constriction velocity of 28% (median 33%) following concussion which decreased over the course of recovery, returning to pre-injury or below pre-injury measurements. Six of seven of the concussed athletes completed NPC and AA assessments at both pre-season and post-injury timepoints. In contrast to the PLR findings, both NPC and AA measures were normal at post-injury assessments. Reported symptom scores improved throughout recovery, correlating with PLR response recovery, with both returning to pre-injury measurements. Conclusion: Pupil responsivity was found to be significantly enhanced after concussion compared to pre-injury measurements, waning over time during recovery, following a similar trajectory as symptom burden. NPC and AA, which have autonomic contributions and are clinical measures, were normal pre- and post-injury and did not differentiate the concussed state from the uninjured state in our series. Our preliminary results demonstrate that dynamic PLR responses may detect acute autonomic deficits that are not evident via clinical assessments. Further investigation of its potential utility as sensitive and objective biomarker in concussion diagnosis, management and sports clearance is warranted.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1104
Author(s):  
Frederick Robert Carrick ◽  
Sergio F. Azzolino ◽  
Melissa Hunfalvay ◽  
Guido Pagnacco ◽  
Elena Oggero ◽  
...  

The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term changes in brain function secondary to injury should cause a change in the parameters of the PLR. We performed a retrospective clinical review of the PLR of our patients using the BrightLamp Reflex iPhone app. The PLR variables of latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered a concussion and those that had not. There were also significant differences in PLR metrics over the life span and between genders and those subjects with and without symptoms. The differences in PLR metrics are modulated not only by concussion history but also by gender and whether or not the person has symptoms associated with a head injury. A concussive injury to the brain is associated with changes in the PLR that persist over the life span, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making.


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