Differences in the pupillary responses to evening light between children and adolescents.

BACKGROUND: In the mammalian retina, intrinsically-photosensitive retinal ganglion cells (ipRGC) detect light and integrate signals from rods and cones to drive multiple non-visual functions including circadian entrainment and the pupillary light response (PLR). Non-visual photoreception and consequently non-visual sensitivity to light may change across child development. The PLR represents a quick and reliable method for examining non-visual responses to light in children. The purpose of this study was to assess differences in the PLRs to blue and red stimuli, measured one hour prior to bedtime, between children and adolescents. METHODS: Forty healthy participants (8-9 years, n = 21; 15-16 years, n = 19) completed a PLR assessment 1 h before their habitual bedtime. After a 1 h dim-light adaptation period (< 1 lx), baseline pupil diameter was measured in darkness for 30 s, followed by a 10 s exposure to 3.0 × 1013 photons/cm2/s of either red (627 nm) or blue (459 nm) light, and a 40 s recovery in darkness to assess pupillary re-dilation. Subsequently, participants underwent 7 min of dim-light re-adaptation followed by an exposure to the other light condition. Lights were counterbalanced across participants. RESULTS: Across both age groups, maximum pupil constriction was significantly greater (p < 0.001, ηp2 = 0.48) and more sustained (p < 0.001, ηp2 = 0.41) during exposure to blue compared to red light. For adolescents, the post-illumination pupillary response (PIPR), a hallmark of melanopsin function, was larger after blue compared with red light (p = 0.02, d = 0.60). This difference was not observed in children. Across light exposures, children had larger phasic (p < 0.01, ηp2 = 0.20) and maximal (p < 0.01, ηp2 = 0.22) pupil constrictions compared to adolescents. CONCLUSIONS: Blue light elicited a greater and more sustained pupillary response than red light in children and adolescents. However, the overall amplitude of the rod/cone-driven phasic response was greater in children than in adolescents. Our findings using the PLR highlight a higher sensitivity to evening light in children compared to adolescents, and continued maturation of the human non-visual photoreception/system throughout development.

Anisocoria After Direct Light Stimulus is Associated with Poor Outcomes Following Acute Brain Injury.

BACKGROUND: Assessing pupil size and reactivity is the standard of care in neurocritically ill patients. Anisocoria observed in critically ill patients often prompts further investigation and treatment. This study explores anisocoria at rest and after light stimulus determined using quantitative pupillometry as a predictor of discharge modified Rankin Scale (mRS) scores. METHODS: This analysis includes data from an international registry and includes patients with paired (left and right eye) quantitative pupillometry readings linked to discharge mRS scores. Anisocoria was defined as the absolute difference in pupil size using three common cut points (> 0.5 mm, > 1 mm, and > 2 mm). Nonparametric models were constructed to explore patient outcome using three predictors: the presence of anisocoria at rest (in ambient light); the presence of anisocoria after light stimulus; and persistent anisocoria (present both at rest and after light). The primary outcome was discharge mRS score associated with the presence of anisocoria at rest versus after light stimulus using the three commonly defined cut points. RESULTS: This analysis included 152,905 paired observations from 6,654 patients with a mean age of 57.0 (standard deviation 17.9) years, and a median hospital stay of 5 (interquartile range 3-12) days. The mean admission Glasgow Coma Scale score was 12.7 (standard deviation 3.5), and the median discharge mRS score was 2 (interquartile range 0-4). The ranges for absolute differences in pupil diameters were 0-5.76 mm at rest and 0-6.84 mm after light. Using an anisocoria cut point of > 0.5 mm, patients with anisocoria after light had worse median mRS scores (2 [interquartile range 0-4]) than patients with anisocoria at rest (1 [interquartile range 0-3]; P < .0001). Patients with persistent anisocoria had worse median mRS scores (3 [interquartile range 1-4]) than those without persistent anisocoria (1 [interquartile range 0-3]; P < .0001). Similar findings were observed using a cut point for anisocoria of > 1 mm and > 2 mm. CONCLUSIONS: Anisocoria after light is a new biomarker that portends worse outcome than anisocoria at rest. After further validation, anisocoria after light should be considered for inclusion as a reported and trended assessment value.

Automated Pupillometry Is Able to Discriminate Patients with Acute Stroke from Healthy Subjects: An Observational, Cross-Sectional Study.

BACKGROUND: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. METHODS: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable's ß coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. RESULTS: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. CONCLUSIONS: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS.

Quantitative Pupillometry: Clinical Applications for the Internist.

From the time of Galen, examination of the pupillary light reflex has been a standard of care across the continuum of health care. The growing body of evidence overwhelmingly supports the use of quantitative pupillometry over subjective examination with flashlight or penlight. At current time, pupillometers have become standard of care in many hospitals across 6 continents. This review paper provides an overview and rationale for pupillometer use and highlights literature supporting pupillometer-derived measures of the pupillary light reflex in both neurological and non-neurological patients across the health care continuum.

Normal baseline cardiac autonomic function and increased pupillary parasympathetic tone in patients with vasovagal syncope.

It is controversial whether people with vasovagal syncope (VVS) have abnormal autonomic responses at baseline and whether specific diagnostic manoeuvres have a diagnostic value. We investigated whether the pupillary light reflex and cardiac autonomic tests can be used to identify autonomic dysfunction in volunteers with a medical history of VVS. The study groups included 128 healthy volunteers, of whom 31 reported a history of typical VVS. The right pupil was evaluated using an automated, commercial infra-red pupillometer under strict conditions. In addition to miosis and mydriasis kinetics, pupil diameters were measured. Heart rate variability at rest and heart rate changes to standing were quantified with high-resolution electrocardiography and designated software. The demographic and clinical characteristics of both groups were statistically similar. Average constriction velocity (ACV) was significantly higher in VVS patients following a univariate analysis (3.83 ± 0.59 vs. 3.56 ± 0.73 mm/s, p = 0.042) and after correcting for potential confounders (p = 0.049). All other pupillometric and heart rate indices were comparable between groups. Patients with a history of VVS depict pupillary parasympathetic overactivity in response to light stimuli, manifested as increased ACV. The prognostic implications of this finding and the significance of using this simple clinical tool to identify patients who are at risk for developing frequent episodes of VVS or physical injuries following a syncope merits further study.

A Study of Pupil Response to Light as a Digital Biomarker of Recent Cannabis Use.

Introduction: Given the traffic safety and occupational injury prevention implications associated with cannabis impairment, there is a need for objective and validated measures of recent cannabis use. Pupillary light response may offer an approach for detection. Method: Eighty-four participants (mean age: 32, 42% female) with daily, occasional, and no-use cannabis use histories participated in pupillary light response tests before and after smoking cannabis ad libitum or relaxing for 15 min (no use). The impact of recent cannabis consumption on trajectories of the pupillary light response was modeled using functional data analysis tools. Logistic regression models for detecting recent cannabis use were compared, and average pupil trajectories across cannabis use groups and times since light test administration were estimated. Results: Models revealed small, significant differences in pupil response to light after cannabis use comparing the occasional use group to the no-use control group, and similar statistically significant differences in pupil response patterns comparing the daily use group to the no-use comparison group. Trajectories of pupillary light response estimated using functional data analysis found that acute cannabis smoking was associated with less initial and sustained pupil constriction compared to no cannabis smoking. Conclusion: These analyses show the promise of pairing pupillary light response and functional data analysis methods to assess recent cannabis use.

Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.

Introduction: The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. Methods and results: We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. Discussion: This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.

Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

The value of pupillary diameter in evaluating pain perception after awakening in patients undergoing general anesthesia during orthopedic surgery.

BACKGROUND: The pupillary response to tetanic electrical stimulation reflects the balance between nociceptive stimulation and analgesia. Although pupillary pain index (PPI) was utilized to predict postoperative pain, it depended on tetanic stimulation and was complex. We aim to describe the potential relationship between PD in the presence of surgical stimulation and pain levels after awakening. METHODS: According to the Verbal Rating Scale (VRS) score after extubation, the patients were divided into painless group (VRS = 0) and pain group (VRS ≥ 1). Pupillary diameter (PD) and pupillary light reflex velocity (PLRV) were compared between two groups when patients entered the operating room (T1), before incision (T2), 10 s after incision (T3), 30 s after incision (T4), 1 h after incision (T5), at the end of surgery (T6), shortly after extubation (T7), and when patients expressed pain clearly (T8). The magnitude of PD change (ΔPD) compared to the baseline value after anesthesia induction (T2) was calculated. The correlations between pupillary parameters and pain after awakening were calculated. RESULTS: Patients with VRS ≥ 1 had greater PD than painless patients at T3-7 (P = 0.04, 0.04, 0.003, <0.001, <0.001), and it was positively correlated with VRS score after awakening at T4-7 (r = 0.188, 0.217, 0.684, 0.721). The ability of T6ΔPD to predict VRS ≥ 1 was strong [threshold: 20.53%, area under the curve (AUC): 0.93, 95% confidence interval (CI): 0.89-0.97 ]. CONCLUSION: Our study indicates that PD is a useful index to direct the individualized analgesics used during operation, to better avoid the occurrence of pain during the postoperative emergence period. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000040908, registration date: 15/12/2020).

The Role of Automated Infrared Pupillometry in Traumatic Brain Injury: A Narrative Review.

Pupillometry, an integral component of neurological examination, serves to evaluate both pupil size and reactivity. The conventional manual assessment exhibits inherent limitations, thereby necessitating the development of portable automated infrared pupillometers (PAIPs). Leveraging infrared technology, these devices provide an objective assessment, proving valuable in the context of brain injury for the detection of neuro-worsening and the facilitation of patient monitoring. In cases of mild brain trauma particularly, traditional methods face constraints. Conversely, in severe brain trauma scenarios, PAIPs contribute to neuro-prognostication and non-invasive neuromonitoring. Parameters derived from PAIPs exhibit correlations with changes in intracranial pressure. It is important to acknowledge, however, that PAIPs cannot replace invasive intracranial pressure monitoring while their widespread adoption awaits robust support from clinical studies. Ongoing research endeavors delve into the role of PAIPs in managing critical neuro-worsening in brain trauma patients, underscoring the non-invasive monitoring advantages while emphasizing the imperative for further clinical validation. Future advancements in this domain encompass sophisticated pupillary assessment tools and the integration of smartphone applications, emblematic of a continually evolving landscape.

The use of quantitative pupillometry in brain death determination: preliminary findings.

PURPOSE: Quantitative pupillometry (QP) has been increasingly applied in neurocritical care as an easy-to-use and reliable technique for evaluating the pupillary light reflex (PLR). Here, we report our preliminary findings on using QP for clinical brain death (BD) determination. MATERIALS: This retrospective study included 17 patients ≥ 18 years (mean age, 57.3 years; standard deviation, 15.8 years) with confirmed BD, as defined by German Guidelines for the determination of BD. The PLR was tested using the NPi®-200 Pupillometer (Neuroptics, Laguna Hill, USA), a handheld infrared device automatically tracking and analyzing pupil dynamics over 3 s. In addition, pupil diameter and neurological pupil index (NPi) were also evaluated. RESULTS: Intracerebral bleeding, subarachnoid hemorrhage, and hypoxic encephalopathy were the most prevalent causes of BD. In all patients, the NPi was 0 for both eyes, indicating the cessation of mid-brain function. The mean diameter was 4.9 mm (± 1.3) for the right pupil and 5.2 mm (±1.2) for the left pupil. CONCLUSIONS: QP is a valuable tool for the BD certification process to assess the loss of PLR due to the cessation of brain stem function. Furthermore, implementing QP before the withdrawal of life-sustaining therapy in brain-injured patients may reduce the rate of missed organ donation opportunities. Further studies are warranted to substantiate the feasibility and potential of this technique in treating patients and identify suitable candidates for this technique during the BD certification process.

Feasibility of USG-Guided Objective Initial Assessment of Pupillary Size and Pupillary Reflexes Versus Clinical Examination in Patients With Altered Mental Status: A Cross-Sectional Study.

BACKGROUND: Pupillary assessment is an important part of the neurological assessment which provides vital information in critically ill patients. However, clinical pupillary assessment is subjective. The ultrasound-guided pupillary examination is objective. There are limited pieces of literature regarding its use in assessing patients with altered mental status. So, we studied the extent of agreement of B-mode ultrasound with clinical examination for assessment of the pupillary size and reflex in patients with altered mental status. OBJECTIVES: The primary objective was to determine the extent of agreement between clinical examination and ultrasound-based examination for assessing pupillary reflex and size in patients with altered mental status in two settings (trauma and non-trauma patients). METHODS: Exactly 200 subjects (158 males, mean [range] age 43.56 [18-92 years]) with no history of partial globe rupture or dementia were included in this cross-sectional study from March 2019 to March 2020. B-mode ultrasound was performed with the subject's eyes closed using a 7-12 MHz linear probe and a standardized light stimulus. ICC score, paired t-test, kappa, Wilcoxon signed-rank test, and Bland-Altman plots were used for statistical analysis. RESULTS: The clinical-USG agreement for pupillary light reflex examination (Pupillary Diameter [PD] at rest, after direct light stimulation [Dstim ] and consensual light stimulation [Cstim ]) was excellent (ICC, 0.93-0.96). The Kappa coefficient (0.74 ± 0.07) showed an agreement of 87.36% between clinical and USG examination for pupillary reflex (reactive or non-reactive). CONCLUSION: USG-guided pupillary examination proves to be a better adjunct to neurological assessment in patients with altered mental status.

Overlooked evidence for transmission deficit of pupillary light reflex can be secondary to trigeminal nerve ganglion degeneration following subarachnoid hemorrhage; preliminary experimental study.

OBJECTIVE: Although the effect of oculomotor and cervical sympathetic networks on pupil diameter is well known; the effect of the trigeminal nerve on pupil diameter has not been investigated yet. This subject was investigated. MATERIALS AND METHODS: Five of 23 rabbits were used as a control group (GI; n = 5); 0.5 ccs saline solution into cisterna magna injected animals used as SHAM (GII; n = 5); autologous blood injected to produce SAH used as the study group (GIII; n = 13) and followed up three weeks. Light-stimulated pupil diameters were measured with an ocular tomography device before, middle, and at the end of the experiment. Considering the sclera area/pupil area ratio index (PRI) as the pupillary reaction area, we used this equation for the pupil's rush to light. Degenerated neuron densities of trigeminal ganglia and pupil diameters compared with the Mann-Whitney U test. RESULTS: The PRI, degenerated neuron density of trigeminal ganglia (n/mm3) were: (2.034 ± 0.301)/(13 ± 3) in GI; (1.678 ± 0.211)/(46 ± 9) in GII; and (0.941 ± 0.136)/(112 ± 21) in GIII. P-values between groups as: p < 0.005 in GI/GII; p < 0.0001 in GII/GIII and p < 0.00001 in GI/GIII. CONCLUSION: Light stimulates the cornea which is innervated by the trigeminal nerves. This experimental study indicates that the pupil remains mydriatic as the cornea is damaged by trigeminal ischemia following SAH and blocks the light flow.

Linear integration of multisensory signals in the pupil.

The pupil of the eye responds to various salient signals from different modalities, but there is no consensus on how these pupillary responses are integrated when multiple signals appear simultaneously. Both linear and nonlinear integration have been found previously. The current study aimed to reexamine the nature of pupillary integration, and specifically focused on the early, transient pupillary responses due to its close relationship with orienting. To separate the early pupillary responses out of the pupil time series, we adopted a pupil oscillation paradigm in which sensory stimuli were periodically presented. The simulation analysis confirmed that the amplitude of the pupil oscillation, induced by stimuli repeatedly presented at relatively high rates, can precisely reflect the early, transient pupillary responses without involving the late and sustained pupillary responses. The experimental results then showed that the amplitude of pupil oscillation induced by a series of simultaneous audiovisual stimuli equaled to a linear summation of the oscillatory amplitudes when unisensory stimuli were presented alone. Moreover, the tonic arousal levels, indicated by the baseline pupil size, cannot shift the summation from linear to nonlinear. These findings together support the additive nature of multisensory pupillary integration for the early, orienting-related pupillary responses. The additive nature of pupillary integration further implies that multiple pupillary responses may be independent of each other, irrespective of their potential cognitive and neural drivers.

Time-on-task effects on human pupillary and saccadic metrics after theta burst transcranial magnetic stimulation over the frontal eye field.

Pupil size undergoes constant changes primarily influenced by ambient luminance. These changes are referred to as the pupillary light reflex (PLR), where the pupil transiently constricts in response to light. PLR kinematics provides valuable insights into autonomic nervous system function and have significant clinical applications. Recent research indicates that attention plays a role in modulating the PLR, and the circuit involving the frontal eye field (FEF) and superior colliculus is causally involved in controlling this pupillary modulation. However, there is limited research exploring the role of the human FEF in these pupillary responses, and its impact on PLR metrics remains unexplored. Additionally, although the protocol of continuous theta-burst stimulation (cTBS) is well-established, the period of disruption after cTBS is yet to be examined in pupillary responses. Our study aimed to investigate the effects of FEF cTBS on pupillary and saccadic metrics in relation to time spent performing a task (referred to as time-on-task). We presented a bright stimulus to induce the PLR in visual- and memory-delay saccade tasks following cTBS over the right FEF or vertex. FEF cTBS, compared to vertex cTBS, resulted in decreased baseline pupil size, peak constriction velocities, and amplitude. Furthermore, the time-on-task effects on baseline pupil size, peak amplitude, and peak time differed between the two stimulation conditions. In contrast, the time-on-task effects on saccadic metrics were less pronounced between the two conditions. In summary, our study provides the first evidence that FEF cTBS affects human PLR metrics and that these effects are modulated by time-on-task.

A smartphone pupillometry tool for detection of acute large vessel occlusion.

OBJECTIVES: Pupillary light reflex (PLR) parameters can be used as quantitative biomarkers of neurological function. Since digital infrared pupillometry is expensive, we sought to examine alterations in PLR parameters using a smartphone quantitative pupillometry platform in subjects with acute ischemic stroke (AIS). MATERIALS AND METHODS: Patients were enrolled if they presented to the emergency department as a stroke code activation and had evidence of a large vessel occlusion (LVO) on computed tomography angiography. Controls were enrolled from hospital staff. A smartphone pupillometer was used in AIS patients with LVO pre-mechanical thrombectomy, immediately post-thrombectomy, and at 24 h post-thrombectomy. Clinical and demographic data were collected, along with the proprietary Neurological Pupil index (NPi) score from the NPi-200 digital infrared pupillometer. PLR parameters were compared using mean differences. The absolute and non-absolute inter-eye difference in each parameter for each subject were also analyzed by measuring 1 - (R:L) to determine alteration in the equilibrium between subject pupils. The NPi was analyzed for mean differences between cohorts. RESULTS: Healthy controls (n = 132) and AIS patients (n = 31) were enrolled. Significant differences were observed in PLR parameters for healthy subjects when compared to pre-thrombectomy subjects in both mean and absolute inter-eye differences after post hoc Bonferroni correction. The proprietary NPi score was not significantly different for all groups and comparisons. CONCLUSIONS: Significant alterations in the PLR were observed in AIS patients with LVO before thrombectomy, indicating the potential use of smartphone pupillometry for detection of LVO.

The photic blink reflex as an index of photophobia.

Two recent studies of eye closure triggered by intense luminance increase suggest that this behavior reflects the melanopsin-based retinal activity known to underlie photophobia, the pathological aversion to light (Kardon, 2012; Kaiser et al., 2021). Early studies of the photic blink reflex (PBR) are reviewed to help guide future research on this possible objective index of photophobia. Electromyographic recordings of the lid-closure muscle, orbicularis oculi, reveal distinct bursts with typical onset latencies of 50 and 80 ms, R50 and R80, respectively. The latter component appears to be especially sensitive to visual signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) and to prior trigeminal nociceptive stimuli. The authors argue that the R80's function, in addition to protecting the eyeballs from physical contact, is to shape the upper and lower eyelids into a narrow slit to restrict incoming light. This serves to prevent retinal bleaching or injury, while allowing continued visual function.

Different rules for binocular combination of luminance flicker in cortical and subcortical pathways.

How does the human brain combine information across the eyes? It has been known for many years that cortical normalization mechanisms implement 'ocularity invariance': equalizing neural responses to spatial patterns presented either monocularly or binocularly. Here, we used a novel combination of electrophysiology, psychophysics, pupillometry, and computational modeling to ask whether this invariance also holds for flickering luminance stimuli with no spatial contrast. We find dramatic violations of ocularity invariance for these stimuli, both in the cortex and also in the subcortical pathways that govern pupil diameter. Specifically, we find substantial binocular facilitation in both pathways with the effect being strongest in the cortex. Near-linear binocular additivity (instead of ocularity invariance) was also found using a perceptual luminance matching task. Ocularity invariance is, therefore, not a ubiquitous feature of visual processing, and the brain appears to repurpose a generic normalization algorithm for different visual functions by adjusting the amount of interocular suppression.

Differences in the Pupillary Responses to Evening Light between Children and Adolescents.

Purpose: To assess differences in the pupillary light responses (PLRs) to blue and red evening lights between children and adolescents. Methods: Forty healthy participants (8-9 years, n=21; 15-16 years, n=19) completed a PLR assessment 1 h before their habitual bedtime. After a 1 h dim-light adaptation period (<1 lux), baseline pupil diameter was measured in darkness for 30 s, followed by a 10 s exposure to 3.0×1013 photons/cm2/s of either red (627 nm) or blue (459 nm) light, and a 40 s recovery in darkness to assess pupillary re-dilation. Subsequently, participants underwent 7 min of dim-light re-adaptation followed by an exposure to the other light condition. Lights were counterbalanced across participants. Results: Across both age groups, maximum pupil constriction was significantly greater (p< 0.001, ηp2=0.48) and more sustained (p< 0.001, ηp2=0.41) during exposure to blue compared to red light. For adolescents, the post-illumination pupillary response (PIPR), a hallmark of melanopsin function, was larger after blue compared with red light (p= 0.02, d=0.60). This difference was not observed in children. Across light exposures, children had larger phasic (p< 0.01, ηp2=0.20) and maximal (p< 0.01, ηp2=0.22) pupil constrictions compared to adolescents. Conclusions: Blue light elicited a greater and more sustained pupillary response than red light across participants. However, the overall amplitude of the rod/cone-driven phasic response was greater in children than in adolescents. Our findings using the PLR highlight a higher sensitivity to evening light in children compared to adolescents, and continued maturation of the human non-visual photoreception/system throughout development.

Daytime autonomic nervous system functions differ among adults with and without insomnia symptoms.

STUDY OBJECTIVES: We gathered data to determine whether daytime assays of the autonomic nervous system would differ between persons with no vs modest insomnia symptoms and would correlate with the severity of insomnia symptoms in patients. METHODS: This report is composed of 2 studies. Study 1 conducted pupillary light reflex (PLR) measurements in community volunteers who were not seeking medical care. Study 2 contrasted PLR and heart rate variability in a different sample of community volunteers and a comparison sample of adults seeking outpatient care for insomnia and psychiatric problems. All measurements were taken between 3 and 5 pm. RESULTS: In Study 1, volunteers with modest insomnia symptom severity had a more rapid PLR average constriction velocity compared with those with no symptoms. In Study 2, lower heart rate variability, indicating higher levels of physiologic arousal, generally were in agreement with faster PLR average constriction velocity, both of which indicate higher levels of arousal. Insomnia symptom severity was highly correlated with faster average constriction velocity in the patient sample. CONCLUSIONS: These studies suggest that (1) daytime measurements of the autonomic nervous system differ between persons with modest vs no insomnia symptoms and (2) insomnia symptom severity is highly correlated with PLR. Daytime measurement of autonomic nervous system activity might allow for daytime point-of-care measurement to characterize the level of physiologic arousal to define a hyperarousal subtype of insomnia disorder. CITATION: McCall WV, Looney SW, Zulfiqar M, et al. Daytime autonomic nervous system functions differ among adults with and without insomnia symptoms. J Clin Sleep Med. 2023;19(11):1885-1893.