ABSTRACT Pseudoneglect, a subtle attentional bias toward the left visual field in neurologically healthy individuals, can be measured with a split-screen method in which a bright stimulus in one hemifield elicits stronger pupil constriction when it appears on the left than on the right (Strauch, C., Romein, C., Naber, M., Van der Stigchel, S., & Ten Brink, A. F. (2022). The orienting response drives pseudoneglect—Evidence from an objective pupillometric method. Cortex, 151, 259–271. https://doi.org/10.1016/j.cortex.2022.03.006). Replications of this method have reported mixed results, including a large Registered Report that replicated the effect with a small effect size (d = −0.31). Given strong left-field biases in the emotional chimeric face test, the present study (n = 53) combined this task with split-screen pupillometry to test whether emotional face processing amplifies pupillary pseudoneglect. Pupillary pseudoneglect was observed during control trials with non-faces (d = −0.36) and was stronger for emotional faces (d = −0.76), but this difference was not significant. A strong left-field bias was confirmed for emotional face judgements (d = −0.76), which did not correlate with pupillary bias (ρ = −0.26), and for a line bisection test (d = −0.47), which also did not correlate with pupillary pseudoneglect (ρ = −0.19). These data support the split-screen pupillometric method for measuring pseudoneglect and replicate a previously-noted pattern that leftward biases across tasks show little statistical relation to one another.

ABSTRACT The light–dark cycle shaped by Earth’s rotation provided the evolutionary conditions under which circadian rhythms emerged. Consistent with this, previous studies indicate that less than 40% of total blind individuals, who lack photic input, entrain to the 24-h cycle, further evidencing the critical role of light as the dominant zeitgeber for circadian alignment. However, this assumption has been tested almost exclusively in temperate, high-latitude regions, where environmental cues vary seasonally. Near the equator, by contrast, photoperiod and temperature cycles remain exceptionally stable. This highlights a fundamental gap: can circadian rhythms in humans remain synchronised without light when environmental temporal cues are highly regular? We addressed this question in 58 blind adults (21–77 years; 43.1% female) living near the equator in Rio Grande do Norte, Brazil (~5°S), who wore wrist actigraphy continuously for 4 weeks. Light sensitivity was assessed through the pupillary light reflex (PLR; 22 PLR-reactive, 36 non-reactive). Applying a semi-supervised machine learning approach to uncover multidimensional patterns without prior categorisation, we identified two distinct phenotypes: a Higher Circadian Stability (HCS; 72%, n = 42) and a Lower Circadian Stability group (LCS; 28%, n = 16). Notably, 64% of PLR-non-reactive individuals (23 of 36) were classified within the HCS group, a proportion approximately 1.6 times higher than previously reported for blind cohorts. These findings demonstrate that, under exceptionally regular equatorial conditions, non-photic cues can sustain a robust circadian entrainment even in the absence of photic input. We propose that environmental regularity promotes the synergy of non-photic timing signals, underscoring ecological context as a relevant component of human circadian temporal organisation.

Pupil reflexes generate the peripheral drift illusion due to ON/OFF motion responses.

Exploratory analysis of pupillography-based machine learning for assessing autonomic dysfunction in multiple sclerosis.

ABSTRACTAimOut‐of‐hospital cardiac arrest (OHCA) carries a poor prognosis despite advances in cardiopulmonary resuscitation (CPR). Traditional prognostic factors have limited accuracy, and “signs of life,” including gasping, pupillary light reflex (PLR), and CPR‐induced consciousness (CPRIC), have been proposed as prognostic markers. We conducted a systematic review and meta‐analysis to evaluate the association between signs of life and outcomes in OHCA.MethodsPubMed, MEDLINE, and Web of Science were systematically searched. Eligible studies included adult patients with OHCA of presumed medical origin reporting survival or neurological outcomes in relation to signs of life. Study quality was assessed using the Newcastle–Ottawa Scale. Pooled odds ratios with 95% confidence intervals were calculated using a random‐effects model.ResultsEight cohort studies, including 4,862 patients, were analyzed. All studies were of good methodological quality. The presence of signs of life was associated with higher survival and favorable neurological outcomes within 30 days after cardiac arrest (CA). Similar associations were observed for longer‐term survival, although evidence for longer‐term neurological outcomes was limited.ConclusionSigns of life during CA or CPR were consistently associated with improved survival and favorable neurological outcomes in patients with OHCA, both within 30 days and beyond 90 days. These findings suggest that signs of life may have prognostic value; however, their applicability may vary depending on clinical context. Systematic documentation of signs of life may be considered in standardized reporting frameworks.

Seamless integration of visual, vestibular, and somatosensory (VVS) systems is key to human movement control. Emerging evidence suggests autonomic nervous system (ANS) function may influence this integration, yet no studies have examined the relationship between ANS activity, indexed by the pupil light reflex, and VVS function. 90 healthy adults (aged 20 - 88years old) were recruited for this prospective cohort study. ANS function was quantified using pupil light reflex, where response delay, maximum pupil constriction and dilation velocities were recorded. VVS system function was quantified via visual-vestibular testing, including smooth pursuit and voluntary saccades, while somatosensory function was quantified using an Active Movement Extent Discrimination Assessment protocol. Multivariate multiple regression analysis was conducted in RStudio with significance set at p < .05. Follow-up univariate analysis of variance was conducted. VVS performance under differing autonomic profiles - Coactivation, Co-inhibition, Parasympathetic-Dominant and Sympathetic-Dominant - was assessed using one-way analysis of variance. Pupil response delay, maximum pupil constriction and age all significantly predicted combined VVS function (p = .01, p=<.01, p=<.01, respectively), with follow-up univariate analyses demonstrating small-to-moderate effects across individual VVS outcomes (ηp2=0.05 to 0.25). ANS profile of Co-inhibition was significantly correlated with worse VVS performance. This research highlights not just the need to consider ANS function in human movement control but also the ANS profile of the individual at rest. The identification of ANS Co-inhibition as a maladaptive profile in the context of VVS integration challenges existing frameworks that treat VVS and ANS as independent contributors to human movement control.

The prognostic role of quantitative pupillometry in comatose patients after cardiac arrest (CA) has been recently described, but data on quantitative pupillary light reflex (qPLR) are limited, especially in a multimodal approach and regarding good outcome. We assessed qPLR correlations with clinical features, electroencephalogram (EEG), somatosensory evoked potentials (SSEPs), and neuron-specific enolase (NSE), as well as qPLR prognostic values toward poor and good outcomes. Bicentric study (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland and Cochin Hospital, Paris, France), analyzing prospective registries of comatose adults with pupillometry parameters obtained during the first 48-72 hours after CA. Neurological Pupil index (NPi), lowest (minimum qPLR), and highest values (maximum qPLR) of qPLR were collected. Predictive performances in terms of Cerebral Performance Categories (CPCs) level at 3 months (good outcome: CPC 1-2) were calculated. None. Between 2020 and 2024, 442 patients were included. Minimum and maximum qPLRs were significantly lower in case of early myoclonus ( p < 0.001), bilateral N20 SSEP absence ( p < 0.001), unreactive EEG ( p < 0.001), and epileptiform EEG ( p = 0.03 and 0.05). qPLR was also significantly lower with suppressed EEG, compared with discontinuous and continuous background ( p < 0.001). Serum NSE level at 48 hours was significantly correlated with minimum (Spearman Rho = -0.283; p < 0.001) and maximum qPLRs ( R = -0.444; p < 0.001). Minimum qPLR less than 2% (96.4% specificity, 23.6% sensitivity), maximum qPLR less than 13% (96.4% specificity, 19.0% sensitivity), and NPi less than or equal to 2 (99% specificity, 34% sensitivity) robustly correlated with poor outcome. Notably, qualitative PLR had higher sensitivity than minimum and maximum qPLRs (38.9 vs. 23.6 and 19.0%, respectively; p < 0.001) with comparable specificity. A minimum qPLR greater than 9.5% (83.2% specificity, 31.1% sensitivity) and a maximum qPLR greater than 25.5% (62.2% specificity, 65.5% sensitivity) correlated with good outcome. In comatose patients after CA, qPLR is tightly correlated with other prognostic markers; low qPLR and NPi less than or equal to 2 appeared highly specific for poor outcome, but performances do not exceed that of clinical PLR. Finally, high qPLR remained limited in predicting a good outcome.

Previous studies have shown those with a history of a traumatic brain injury (TBI) have altered pupillary light responses compared with those without a history of TBI. Those with a history of TBI are also more likely to have accommodative deficits. We investigated the relationship between light-evoked pupil dynamics and accommodative function in individuals who have previously experienced a TBI. A total of 17 participants with a history of mild TBI were recruited. Pupil metrics were measured using a commercial pupillometer and included baseline diameter, latency, constriction amplitude, average constriction velocity, peak constriction velocity and peak dilation velocity. Accommodative function was assessed using clinical measurements of facility and amplitude. Pupil metrics were compared among those with versus without accommodative dysfunction. One-way ANCOVA testing (controlling for age and time since most recent TBI) comparing groups with and without accommodative dysfunction showed that those with accommodative dysfunction had significantly larger light-evoked pupil constriction amplitudes (p = 0.037) and significantly faster average constriction velocity (p = 0.007) compared with those without accommodative dysfunction. No significant differences were observed for other pupil metrics (p > 0.05 for all). ANCOVA testing (controlling for age and time since TBI) to determine whether decreased amplitude of accommodation or facility was more strongly related to the differences in pupil metrics observed between those with versus without accommodative dysfunction, showed significantly larger light-evoked pupil constriction amplitudes (p = 0.007) and significantly faster average constriction velocity (p = 0.002) among those with reduced accommodative facility compared with those with normal accommodative facility. No statistically significant differences were observed between those with reduced versus normal accommodative amplitude (p ≥ 0.07). Among all participants, monocular accommodative facility measures were significantly correlated with greater pupil constriction amplitude (right eye: rho = -0.721, p = 0.001; left eye: rho = -0.65, p = 0.005), and greater average constriction velocity (right eye: rho = -0.58, p = 0.015; left eye: rho = -0.57, p = 0.016). The results of this small-sample study suggest that accommodative function and light-evoked pupillary dynamics are correlated in individuals with a history of TBI. Those with accommodative dysfunction showed greater pupil constriction amplitudes and velocities and this relationship may reflect shared autonomic or oculomotor mechanisms.

Changes in Melanopsin expression in the iris after corneal abrasion in an experimental rat model.

To examine the acute and longitudinal effects of repetitive transcranial magnetic stimulation (rTMS) on-autonomic nervous system measures (ANS)-heart rate variability (HRV) and pupillary light reflex (PLR)-in adults with major depressive disorder (MDD). This pilot study explored the feasibility of measurement and associations with clinical outcomes. Thirteen adults undergoing rTMS for MDD participated in a single-blind, randomized, sham-controlled initial session, followed by 30 open-label treatments. HRV indices [root mean square of successive differences (RMSSD), high-frequency power in normalized units (HFnu)] were recorded at baseline, during stimulation, and biweekly; PLR indices were assessed pre- and post-treatment at rTMS session #1 and at endpoint. Depression severity was measured with the Hamilton Rating Scale for Depression (HRSD). Mixed-effects linear models evaluated changes over time; correlations examined associations between ANS measures and symptom improvement. HRSD scores improved significantly across treatment (P<0.01), with 4 remitters, 4 responders, and 5 nonresponders. No significant changes were observed in HRV or PLR for the entire sample over the treatment course. However, PLR maximum constriction velocity (MCV) decreased in the active condition versus sham at rTMS session #1 (P<0.05). There were no significant correlations between changes in HRSD scores and changes in either HRV or PLR variables. Compared with sham stimulation, rTMS induced hyperacute parasympathetic effects on the ANS, as measured by PLR MCV, but this effect was short-lived. ANS measures showed no overall group change over the course of rTMS and no relationship to improvement in depression symptoms.

Understanding the risk factors of driving dilemmas at urban tunnel exits adjoining diverging areas: A naturalistic study.

Characterizing autonomic nervous system alterations in hospitalized patients with delirium: A scoping review.

Autonomic responses to sensory stimuli are altered in autism, yet little is known about how multisensory input modulates these responses. This study examined whether auditory stimuli affect the pupil light reflex (PLR), a parasympathetically driven response to light, in autistic and non-autistic children. Pupillometry was used to measure responses to visual-only (V), auditory-only (A), and audiovisual (AV) stimuli in 72 children aged 8-14 years (34 non-autistic, 38 autistic). We hypothesized that auditory input would attenuate pupil constriction in non-autistic children in the AV condition and that this cross-modal modulation might differ in autism, reflecting altered sensory-autonomic functioning. Across groups, results revealed a consistent pattern: auditory stimuli elicited pupil dilation, visual stimuli evoked constriction and simultaneous AV stimuli led to attenuated constriction relative to visual-only trials. This attenuation lends support to prior findings of multisensory attenuation of the PLR. Time-binned analysis revealed a group effect during the 500-1000 ms post-stimulus window: autistic children showed significantly more positive baseline-corrected pupil responses across conditions (i.e., less constriction in V/AV and greater dilation in A), suggesting group differences in the dynamic trajectory of the pupil response. Contrary to expectations, autistic and non-autistic children did not differ significantly on peak constriction or constriction latency within visual conditions. Offering insight into how autistic individuals integrate sensory information and regulate arousal, these findings support the presence of cross-modal modulation of the PLR and suggest that auditory signals influence early-stage visual-autonomic processing similarly across groups.

Evaluation of acute visual changes in the pediatric emergency department: Etiologies and red flags.

The 2025 Korean pediatric advanced life support guideline update introduces clinically important revisions emphasizing airway strategy, physiologic resuscitation targets, post–cardiac arrest hemodynamics, neuroprotection, and extracorporeal support. In out-of-hospital pediatric cardiac arrest, bag-mask ventilation is now suggested over endotracheal intubation or supraglottic airway placement. In in-hospital arrest, evidence is insufficient to favor bag-mask ventilation versus advanced airways; however, endotracheal intubation or supraglottic airway insertion is reasonable when performed with minimal interruption or when bag-mask ventilation is ineffective. For patients with an advanced airway in place, age-adjusted ventilation rates are proposed to avoid hypoventilation and hyperventilation: 30/min (<1 yr), 20–30/min (1–8 yr), and 10–20/min (8–18 yr in healthcare settings). When invasive arterial monitoring is available during in-hospital cardiac arrest, target diastolic blood pressure is ≥25 mmHg in infants and ≥30 mmHg in children ≥1 year. After return of spontaneous circulation, systolic blood pressure during the first 6 hours should be maintained above the age-specific 10th percentile. Neuroprognostication should be multimodal, incorporating serial examinations, electroencephalography (up to 72 hours), early computed tomography (<24 hours), magnetic resonance imaging (72 hours to 2 weeks), lactate trends, and pupillary reflexes. Extracorporeal cardiopulmonary resuscitation (CPR) is limited to appropriately resourced hospitals and may be considered for selected in-hospital arrests (e.g., cardiac disease) unresponsive to conventional CPR; evidence remains insufficient for out-of-hospital use. These revisions shift pediatric resuscitation toward physiology-guided, resource-stratified, and neuroprotective care.

The pupillary light reflex (PLR) is modulated by retinal photoreceptors and influenced by light transmission through the intraocular media (IOM). Variations in IOM transparency, due to scattering, transmittance, or yellowing, can affect visual and non-visual functions; however, their impact on photoreceptor-specific PLR remains unclear. In this study, we measured PLR responses selectively driven by Melanopsin, S-cones, and L+M cones in young adults using silent substitution and chromatic pupillometry. These pupillary measurements were correlated with individual IOM properties. Additionally, we simulated changes with external filters. Our findings indicate that the degree of scattering or transmittance impacts the cone-driven responses. Notably, increased scattering consistently slowed S-cone-driven responses across both experiments. Melanopsin-driven PLR and yellowing showed no significant effects. These results suggest that normal variations in IOM transparency modulate cone-mediated PLR dynamics but do not affect melanopsin responses, thereby contributing to individual differences in pupil behavior and potentially influencing ophthalmic and neurological assessments that rely on optical stimuli.

The methadone:metabolite ratio (MMR) is a laboratory value assessed pre-dose to discriminate between individuals who are rapid or slow metabolizers. It is a proposed alternative to peak:trough serum methadone ratios to assess the impact of individual genetics on methadone metabolism to guide dosing frequency of methadone in adults. Pregnancy represents a state of dynamic metabolism of many drugs, including methadone, but there is little study of the MMR in pregnancy. We aimed to (1) assess how well MMR assessed during methadone initiation in pregnancy correlates with the gold standard of assessing metabolism (peak:trough ratio which requires 2 blood draws), (2) describe MMR as assessed during initiation of methadone across gestation to see if it reflected altered metabolism in pregnancy, and (3) determine whether differences in MMR correlated with measures of therapeutic effect, which would suggest it is a potentially useful tool to guide dosing regimens of methadone in pregnancy. This is a prospective study of pregnant patients with singleton gestation admitted for methadone initiation starting with a dose of 30mg and increasing by 10mg every 4 hours as needed based on withdrawal symptoms, with an increase in the daily dose the next day. Plasma samples of methadone and the metabolite EDDP were obtained pre-morning dose and 4 hours post-dose. MMR was evaluated both as a continuous variable and categorical: MMR<5: ultra-rapid metabolizer, MMR 5-11: extensive metabolizer, MMR 12-16: intermediate metabolizer, MMR≥16 ultra-slow metabolizer. Additional endpoints of Clinical Opioid Withdrawal Scale (COWS) and pupil dilation were assessed. Multivariable generalized estimating equations used for analyses. From March 2023 to May 2024 31 patients with 107 samples available were included. MMRtrough increased with methadone dose the prior 24 hours [0.01 (0.01, 0.02), P<0.001] and decreased with advancing trimester of admission [-2.95 (-5.00, -0.90), P=0.005 for second vs. first trimester and -2.78 (-4.98, -0.58), P=0.01 for third vs. first trimester]. A greater proportion of results reflected an ultra-rapid metabolizing state in the second and third trimester compared with the first (77% and 71% vs. 23%, P<0.001). MMR was highly correlated with log-corrected methadone peak:trough throughout gestation, regardless of trimester [B coefficient -3.36 (-5.65 to -1.06), P=0.004]. Regarding clinical effects-pupil dilation was significantly associated with methadone dose, with an expected pupilar constriction associated with increasing methadone dose [-0.55 (-0.75, -0.34) P<0.001]. There was significantly reduced pupillary constriction (relative larger post-dose diameter) identified in the third trimester versus first [adjusted mean difference 0.67 (0.20, 1.13)]. There was no significant association between MMR and pupillary change. MMR was associated with time needed to achieve a stable dose, with those who were extensive metabolizers requiring greater time to stable dose compared with ultra-rapid metabolizers [mean difference 3.37 (0.61-6.13) d, P=0.02]. Although MMR has historically been used to reflect genetic variants impacting methadone metabolism, in pregnancy it reflects the increased metabolism with advancing gestation and is associated with clinical/therapeutic effect. MMR may be a useful marker to guide methadone dosing protocols in pregnancy to optimize therapeutic effect.

Both ophthalmic and retinal artery occlusion and caudate nucleus infarction are forms of arterial ischemic stroke, which are rare in adolescents. The causal relationship between these two events is still unclear. A 17-year-old Han Chinese boy presented with vision loss in his left eye for 24h and was diagnosed with ophthalmic and retinal artery occlusion. The ophthalmologic examination showed no light perception and no pupil light reflex. The fundus examination revealed a cherry-red spot at the macula with white ischemic retina and optic disc. Intra-arterial thrombolysis (urokinase 100,000 units and papaverine 30mg) was performed 24h after symptom onset. On the second day postoperatively, the patient complained of headache and dizziness, and magnetic resonance imaging of the brain revealed subacute caudate nucleus infarction. Etiological workup including cardiac, coagulation, autoimmune, and inflammatory tests was negative except for borderline elevated cholesterol and positive CMV IgG with no evidence of active infection. Despite continuous treatment, the vision in his left eye remained sense light 2months after he was discharged. Ophthalmic and retinal artery occlusion is an ophthalmologic emergency and deserves more aggressive treatment in adolescents. Caudate nucleus infarction is also an emergency that impairs health. In this adolescent case, the concurrent occurrence of these two events was rare, but the causal relationship remains unproven. Further etiological clarification is needed. More attention should be paid to the general condition of adolescents, and provide comprehensive assessments, treatment, and follow-ups.

Human retinal organoids functionally bridge a transected optic nerve in a rat model.

During dark adaptation, pupil size changes in association with visual adaptation processes; however, the influence of diurnal phase (daytime vs nighttime) and aging on these changes remains unclear. In this study, we examined pupil size changes during dark adaptation across the daytime and nighttime in young, middle-aged, and aged C57BL/6N mice. In young mice, pupil size reached a maximum shortly after the onset of dark adaptation and then gradually decreased during the daytime, whereas it remained dilated during the nighttime. Furthermore, dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly attenuated the gradual pupillary constriction following pupil dilation during dark adaptation in the daytime, suggesting a possible involvement of dopaminergic signaling in the later phase of the response. In middle-aged mice, pupillary light reflex-evoked constriction was preserved; however, the early (rapid) phase of constriction following the initial dilation during daytime dark adaptation was impaired, whereas the later (delayed) phase remained largely comparable to that in young mice, suggesting age-related alterations in regulatory mechanisms rather than a loss of constriction capacity. Pharmacological analyses further suggested that distinct neural mechanisms may differentially contribute to these temporal phases. In aged mice, maximal pupil dilation during dark adaptation was significantly reduced during both the daytime and nighttime. In addition, aged mice exhibited distinct abnormalities in pupil dilation immediately after the onset of dark adaptation during the nighttime, indicating mechanisms that differ from those observed in middle-aged mice. Together, these results demonstrate that pupillary dynamics during dark adaptation are modulated by diurnal phase and progressively altered with aging. Thus, analysis of pupil dynamics during dark adaptation may provide a useful approach for detecting age-related changes in neural function.