Pupil diameter as an indicator of sound pair familiarity after statistically structured auditory sequence.

Inspired by recent findings in the visual domain, we investigated whether the stimulus-evoked pupil dilation reflects temporal statistical regularities in sequences of auditory stimuli. We conducted two preregistered pupillometry experiments (experiment 1, n = 30, 21 females; experiment 2, n = 31, 22 females). In both experiments, human participants listened to sequences of spoken vowels in two conditions. In the first condition, the stimuli were presented in a random order and, in the second condition, the same stimuli were presented in a sequence structured in pairs. The second experiment replicated the first experiment with a modified timing and number of stimuli presented and without participants being informed about any sequence structure. The sound-evoked pupil dilation during a subsequent familiarity task indicated that participants learned the auditory vowel pairs of the structured condition. However, pupil diameter during the structured sequence did not differ according to the statistical regularity of the pair structure. This contrasts with similar visual studies, emphasizing the susceptibility of pupil effects during statistically structured sequences to experimental design settings in the auditory domain. In sum, our findings suggest that pupil diameter may serve as an indicator of sound pair familiarity but does not invariably respond to task-irrelevant transition probabilities of auditory sequences.

Evaluating the utility of quantitative pupillometry in a neuro-critical care setting for the monitoring of intracranial pressure: A prospective cohort study.

INTRODUCTION: Assessment of the pupillary light reflex (PLR) is key in intensive care monitoring of neurosurgical patients, particularly for monitoring intracranial pressure (ICP). Quantitative pupillometry using a handheld pupillometer is a reliable method for PLR assessment. However, many variables are derived from such devices. We therefore aimed to assess the performance of these variables at monitoring ICP. METHODS: Sedated patients admitted to neurocritical care in a tertiary neurosurgical centre with invasive ICP monitoring were included. Hourly measurement of ICP, subjective pupillometry (SP) using a pen torch device, and quantitative pupillometry (QP) using a handheld pupillometer were performed. RESULTS: 561 paired ICP, SP and QP pupillary observations from nine patients were obtained (1122 total pupillary observations). SP and QP had a moderate concordance for pupillary size (κ=0.62). SP performed poorly at detecting pupillary size changes (sensitivity=24%). In 40 (3.6%) observations, SP failed to detect a pupillary response whereas QP did. Moderate correlations with ICP were detected for maximum constriction velocity (MCV), dilation velocity (DV), and percentage change in pupillary diameter (%C). Discriminatory ability at an ICP threshold of >22 mmHg was moderate for MCV (AUC=0.631), DV (AUC=0.616), %C (AUC=0.602), and pupillary maximum size (AUC=0.625). CONCLUSION: QP is superior to SP at monitoring pupillary reactivity and changes to pupillary size. Although effect sizes were moderate to weak across assessed variables, our data indicates MCV and %C as the most sensitive variables for monitoring ICP. Further study is required to validate these findings and to establish normal range cut-offs for clinical use.

Combining Cardiovascular and Pupil Features Using k-Nearest Neighbor Classifiers to Assess Task Demand, Social Context, and Sentence Accuracy During Listening.

In daily life, both acoustic factors and social context can affect listening effort investment. In laboratory settings, information about listening effort has been deduced from pupil and cardiovascular responses independently. The extent to which these measures can jointly predict listening-related factors is unknown. Here we combined pupil and cardiovascular features to predict acoustic and contextual aspects of speech perception. Data were collected from 29 adults (mean  =  64.6 years, SD  =  9.2) with hearing loss. Participants performed a speech perception task at two individualized signal-to-noise ratios (corresponding to 50% and 80% of sentences correct) and in two social contexts (the presence and absence of two observers). Seven features were extracted per trial: baseline pupil size, peak pupil dilation, mean pupil dilation, interbeat interval, blood volume pulse amplitude, pre-ejection period and pulse arrival time. These features were used to train k-nearest neighbor classifiers to predict task demand, social context and sentence accuracy. The k-fold cross validation on the group-level data revealed above-chance classification accuracies: task demand, 64.4%; social context, 78.3%; and sentence accuracy, 55.1%. However, classification accuracies diminished when the classifiers were trained and tested on data from different participants. Individually trained classifiers (one per participant) performed better than group-level classifiers: 71.7% (SD  =  10.2) for task demand, 88.0% (SD  =  7.5) for social context, and 60.0% (SD  =  13.1) for sentence accuracy. We demonstrated that classifiers trained on group-level physiological data to predict aspects of speech perception generalized poorly to novel participants. Individually calibrated classifiers hold more promise for future applications.

Effect of recurrent task-induced acute stress on task performance, vagally mediated heart rate variability, and task-evoked pupil response.

Advances in wearable sensor technologies can be leveraged to investigate behavioral and physiological responses in task-induced stress environments. Reliable and valid multidimensional assessments are required to detect stress given its multidimensional nature. This study investigated the effect of recurrent task-induced acute stress on task performance, vagally mediated heart variability measures (vmHRV) and task-evoked pupillary response (TEPR). Task performance, vmHRV measures, and TEPR were collected from 32 study participants while they performed a computer-based task in a recurrent task-induced acute stress environment. Mixed-effects modeling was used to assess the sensitivity of each outcome variable to experimental conditions. Repeated measures correlation tests were used to examine associations between outcome variables. Task performance degraded under stress. vmHRV measures were lower in the stress conditions relative to the no stress conditions. TEPR was found to be higher in the stress conditions compared to the no stress conditions. Task performance was negatively associated with the vmHRV measures, and degraded task performance was linked to increased TEPR in the stress conditions. There were positive associations between vmHRV measures. TEPR was negatively associated with vmHRV measures. Although task-induced stress degrades task performance, recurrent exposure to that stress could alter this effect via habituation. Further, our findings suggest that vmHRV measures and TEPR are sensitive enough to quantify psychophysiological responses to recurrent task-induced stress.

Measurements of pupillary unrest using infrared pupillometry fail to detect changes in pain intensity in patients after surgery: a prospective observational study.

PURPOSE: The pupil displays chaotic oscillations, also referred to as pupillary unrest in ambient light (PUAL). As pain has previously been shown to increase pupillary unrest, the quantitative assessment of PUAL has been considered a possible tool to identify and quantify pain. Nevertheless, PUAL is affected by various states, such as vigilance, cognitive load, or emotional arousal, independent of pain. Furthermore, systematically applied opioids are known to reduce PUAL, thus potentially limiting its usefulness to detect pain or changes in pain intensity. To test the hypothesis that PUAL can reliably identify changes in pain intensity in a clinical setting, we measured PUAL in patients experiencing substantial pain relief when regional anesthesia interventions were applied after surgery. METHODS: We conducted an observational study at an academic surgery centre following institutional review board approval. Eighteen patients with unsatisfactory pain control following surgery underwent regional anesthesia procedures to improve pain control. We used infrared pupillometry to assess pupillary unrest before and after the regional block. We then compared the changes in pupillary unrest with the changes in pain scores (numeric rating scale [NRS], range 0-10). RESULTS: Eighteen patients received epidural anesthesia (n = 14) or peripheral nerve blocks (n = 4), resulting in improvement of mean (standard deviation [SD]) NRS pain scores from 7.2 (1.7) to 1.9 (1.8) (difference in means, -2.2; 95% confidence interval [CI], -6.3 to -4.1; P < 0.001). Nevertheless, pupillary unrest did not change as pain decreased; the mean (SD) PUAL was 0.113 (0.062) before analgesia and 0.112 (0.068) after analgesia (difference in means, -0.001; 95% CI, -0.018 to 0.015; P = 0.88). CONCLUSION: In this prospective observational study, pupillometric measurements of pupillary unrest did not identify changes in pain intensity in a postoperative, predominantly opioid-exposed patient population. While the sample size was small, the use of measurements of pupillary unrest to detect and quantify pain has to be questioned.

RéSUMé: OBJECTIF: La pupille affiche des oscillations chaotiques, également appelées fluctuations du diamètre pupillaire (FDP). Comme il a déjà été démontré que la douleur augmente les troubles pupillaires, l'évaluation quantitative des FDP a été envisagée comme outil potentiel pour identifier et quantifier la douleur. Néanmoins, les FDP sont affectées par divers états, tels que la vigilance, la charge cognitive ou l'excitation émotionnelle, indépendamment de la douleur. De plus, nous savons que l'application systématique d'opioïdes réduit les FDP, ce qui limite potentiellement leur utilité pour détecter la douleur ou les changements d'intensité de la douleur. Pour tester l'hypothèse selon laquelle les FDP permettent d'identifier de manière fiable les changements dans l'intensité de la douleur dans un cadre clinique, nous avons mesuré les FDP chez les patient·es manifestant un soulagement substantiel de la douleur lorsque des interventions d'anesthésie régionale ont été appliquées après la chirurgie. MéTHODE: Nous avons mené une étude observationnelle dans un centre de chirurgie universitaire après avoir obtenu l'approbation du comité d'éthique indépendant. Dix-huit patient·es dont le contrôle de la douleur n'était pas satisfaisant à la suite d'une intervention chirurgicale ont bénéficié d'interventions d'anesthésie régionale pour améliorer le contrôle de la douleur. Nous avons utilisé la pupillométrie infrarouge pour évaluer les fluctuations du diamètre pupillaire avant et après le bloc régional. Nous avons ensuite comparé les changements dans les fluctuations pupillaires avec les changements dans les scores de douleur (échelle d'évaluation numérique [EVA], plage de 0 à 10). RéSULTATS: Dix-huit patient·es ont reçu une anesthésie péridurale (n = 14) ou des blocs nerveux périphériques (n = 4), ce qui a entraîné une amélioration des scores de douleur moyens (écart type [ET]) sur l'EVA de 7,2 (1,7) à 1,9 (1,8) (différence de moyennes, −2,2 ; intervalle de confiance [IC] à 95 %, −6,3 à −4,1; P < 0,001). Néanmoins, les fluctuations du diamètre pupillaire n'ont pas changé à mesure que la douleur diminuait; la moyenne (ET) des FDP était de 0,113 (0,062) avant l'analgésie et de 0,112 (0,068) après l'analgésie (différence de moyennes, −0,001; IC 95 %, −0,018 à 0,015; P = 0,88). CONCLUSION: Dans cette étude observationnelle prospective, les mesures pupillométriques des fluctuations du diamètre pupillaire n'ont pas permis d'identifier de changements dans l'intensité de la douleur dans une population de patient·es postopératoires, principalement exposé·es aux opioïdes. Bien que la taille de l'échantillon soit petite, l'utilisation de mesures des fluctuations du diamètre pupillaire pour détecter et quantifier la douleur doit être remise en question.

Study on the correlation between iris blood flow, iris thickness and pupil diameter in the resting state and after pharmacological mydriasis in patients with diabetes mellitus.

BACKGROUND: To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). RESULTS: The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P < 0.05). After pupil dilation, there were no changes in iris blood flow and PD in the T1DM group compared to healthy children, whereas the T2DM group showed a significantly smaller PD compared to healthy adults. Multivariate regression analysis revealed that in the T2DM group, glycated hemoglobin was an independent factor of PD after dilation (ß=-0.490, p = 0.031), with no such factors identified in the T1DM group. CONCLUSION: The insufficiently dilated pupil diameter after drug-induced mydriasis is correlated to the level of glycated hemoglobin among T2DM patients. TRIAL REGISTRATION: The registration number on the clinical trial website was NCT03631108.

Changes in pupil size track self-control failure.

People are more likely to perform poorly on a self-control task following a previous task requiring self-control (ego-depletion), but the mechanism for this effect remains unclear. We used pupillometry to test the role of attentional effort in ego-depletion. We hypothesized that an elevated pupil diameter (PD)-a common physiological measure of effort-during an initial task requiring self-control should be negatively associated with performance on a subsequent control task. To test this hypothesis, participants were first assigned to either a high- or low-demand attention task (manipulation; a standard ego-depletion paradigm), after which all participants completed the same Stroop task. We then separately extracted both sustained (low-frequency) and phasic (high-frequency) changes in PD from both tasks to evaluate possible associations with lapses of cognitive control on the Stroop task. We first show that in the initial task, sustained PD was larger among participants who were assigned to the demanding attention condition. Furthermore, ego-depletion effects were serially mediated by PD: an elevated PD response emerged rapidly among the experimental group during the manipulation, persisted as an elevated baseline response during the Stroop task, and predicted worse accuracy on incongruent trials, revealing a potential indirect pathway to ego-depletion via sustained attention. Secondary analyses revealed another, independent and direct pathway via high levels of transient attentional control: participants who exhibited large phasic responses during the manipulation tended to perform worse on the subsequent Stroop task. We conclude by exploring the neuroscientific implications of these results within the context of current theories of self-control.

Comparison of two pupillometric measures as indicators of cognitive strain and under the influence of screen luminance.

The pupil diameter has been shown to provide insight to a person's experienced cognitive strain. Pupillary light responses, however, make this measure unreliable in uncontrolled settings. Two derived indicators-Index of Cognitive Activity (ICA) and Index of Pupillary Activity (IPA)-aim to 'eliminate' lighting influences, changing based only on the perceived cognitive strain. The IPA potentially offers a valuable alternative to the ICA through its fully transparent calculation, which lifts the restrictions to proprietary software and supported eye trackers. The measures are examined and compared based on two experimental studies; (i) as indicators of cognitive strain during mental arithmetic tasks and (ii) under different conditions of computer screen luminance. Results indicate that neither indicator differentiates between the increasing levels of cognitive strain. Differences in screen luminance are reflected in both indicators, although differently between the conditions. Both results contradict the claims of the indicators and further investigations are thus required.

A disinhibitory circuit mechanism explains a general principle of peak performance during mid-level arousal.

Perceptual decision-making is highly dependent on the momentary arousal state of the brain, which fluctuates over time on a scale of hours, minutes, and even seconds. The textbook relationship between momentary arousal and task performance is captured by an inverted U-shape, as put forward in the Yerkes-Dodson law. This law suggests optimal performance at moderate levels of arousal and impaired performance at low or high arousal levels. However, despite its popularity, the evidence for this relationship in humans is mixed at best. Here, we use pupil-indexed arousal and performance data from various perceptual decision-making tasks to provide converging evidence for the inverted U-shaped relationship between spontaneous arousal fluctuations and performance across different decision types (discrimination, detection) and sensory modalities (visual, auditory). To further understand this relationship, we built a neurobiologically plausible mechanistic model and show that it is possible to reproduce our findings by incorporating two types of interneurons that are both modulated by an arousal signal. The model architecture produces two dynamical regimes under the influence of arousal: one regime in which performance increases with arousal and another regime in which performance decreases with arousal, together forming an inverted U-shaped arousal-performance relationship. We conclude that the inverted U-shaped arousal-performance relationship is a general and robust property of sensory processing. It might be brought about by the influence of arousal on two types of interneurons that together act as a disinhibitory pathway for the neural populations that encode the available sensory evidence used for the decision.

Stability of the retinal image under normal viewing conditions and the implications for neural adaptation.

Previous studies have demonstrated that the visual system adapts to the specific aberration pattern of an individual's eye. Alterations to this pattern can lead to reduced visual performance, even when the Root Mean Square (RMS) of the wavefront error remains constant. However, it is well-established that ocular aberrations are dynamic and can change with factors such as pupil size and accommodation. This raises an intriguing question: can the neural system adapt to continuously changing aberration patterns? To address this question, we measured the ocular aberrations in four subjects under various natural viewing conditions, which included changes in accommodative state and pupil size. We subsequently computed the associated Point Spread Functions (PSFs). For each subject, we examined the stability in the orientation of the PSFs and analyzed the cross-correlation between different PSFs. These findings were then compared to the characteristics of a distribution featuring PSF shapes akin to random variations. Our results indicate that the changes observed in the PSFs are not substantial enough to produce a PSF shape distribution resembling random variations. This lends support to the notion that neural adaptation is indeed a viable mechanism even in response to continuously changing aberration patterns.

Nonlinear changes in pupillary attentional orienting responses across the lifespan.

The cognitive aging process is not necessarily linear. Central task-evoked pupillary responses, representing a brainstem-pupil relationship, may vary across the lifespan. Thus we examined, in 75 adults ranging in age from 19 to 86, whether task-evoked pupillary responses to an attention task may serve in as an index of cognitive aging. This is because the locus coeruleus (LC), located in the brainstem, is not only among the earliest sites of degeneration in pathological aging, but also supports both attentional and pupillary behaviors. We assessed brief, task-evoked phasic attentional orienting to behaviorally relevant and irrelevant auditory tones, stimuli known specifically to recruit the LC in the brainstem and evoke pupillary responses. Due to potential nonlinear changes across the lifespan, we used a novel data-driven analysis on 6 dynamic pupillary behaviors on 10% of the data to reveal cut off points that best characterized the three age bands: young (19-41 years old), middle aged (42-68 years old), and older adults (69 + years old). Follow-up analyses on independent data, the remaining 90%, revealed age-related changes such as monotonic decreases in tonic pupillary diameter and dynamic range, along with curvilinear phasic pupillary responses to the behaviorally relevant target events, increasing in the middle-aged group and then decreasing in the older group. Additionally, the older group showed decreased differentiation of pupillary responses between target and distractor events. This pattern is consistent with potential compensatory LC activity in midlife that is diminished in old age, resulting in decreased adaptive gain. Beyond regulating responses to light, pupillary dynamics reveal a nonlinear capacity for neurally mediated gain across the lifespan, thus providing evidence in support of the LC adaptive gain hypothesis.

Eye pupil signals life motion perception.

The ability to readily detect and recognize biological motion (BM) is fundamental to survival and interpersonal communication. However, perception of BM is strongly disrupted when it is shown upside down. This well-known inversion effect is proposed to be caused by a life motion detection mechanism highly tuned to gravity-compatible motion cues. In the current study, we assessed the inversion effect in BM perception using a no-report pupillometry. We found that the pupil size was significantly enlarged when observers viewed upright BMs (gravity-compatible) compared with the inverted counterparts (gravity-incompatible). Importantly, such an effect critically depended on the dynamic biological characteristics, and could be extended to local feet motion signals. These findings demonstrate that the eye pupil can signal gravity-dependent life motion perception. More importantly, with the convenience, objectivity, and noninvasiveness of pupillometry, the current study paves the way for the potential application of pupillary responses in detecting the deficiency of life motion perception in individuals with socio-cognitive disorders.

Pupil Dilation Reflects Perceptual Priorities During a Receptive Speech Task.

OBJECTIVES: The listening demand incurred by speech perception fluctuates in normal conversation. At the acoustic-phonetic level, natural variation in pronunciation acts as speedbumps to accurate lexical selection. Any given utterance may be more or less phonetically ambiguous-a problem that must be resolved by the listener to choose the correct word. This becomes especially apparent when considering two common speech registers-clear and casual-that have characteristically different levels of phonetic ambiguity. Clear speech prioritizes intelligibility through hyperarticulation which results in less ambiguity at the phonetic level, while casual speech tends to have a more collapsed acoustic space. We hypothesized that listeners would invest greater cognitive resources while listening to casual speech to resolve the increased amount of phonetic ambiguity, as compared with clear speech. To this end, we used pupillometry as an online measure of listening effort during perception of clear and casual continuous speech in two background conditions: quiet and noise. DESIGN: Forty-eight participants performed a probe detection task while listening to spoken, nonsensical sentences (masked and unmasked) while recording pupil size. Pupil size was modeled using growth curve analysis to capture the dynamics of the pupil response as the sentence unfolded. RESULTS: Pupil size during listening was sensitive to the presence of noise and speech register (clear/casual). Unsurprisingly, listeners had overall larger pupil dilations during speech perception in noise, replicating earlier work. The pupil dilation pattern for clear and casual sentences was considerably more complex. Pupil dilation during clear speech trials was slightly larger than for casual speech, across quiet and noisy backgrounds. CONCLUSIONS: We suggest that listener motivation could explain the larger pupil dilations to clearly spoken speech. We propose that, bounded by the context of this task, listeners devoted more resources to perceiving the speech signal with the greatest acoustic/phonetic fidelity. Further, we unexpectedly found systematic differences in pupil dilation preceding the onset of the spoken sentences. Together, these data demonstrate that the pupillary system is not merely reactive but also adaptive-sensitive to both task structure and listener motivation to maximize accurate perception in a limited resource system.

Self-regulating arousal via pupil-based biofeedback.

The brain's arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus, one of the key regulators of central arousal and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the locus coeruleus and other brainstem structures involved in arousal control. Furthermore, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brain's arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioural and clinical applications across various domains, including stress-related and anxiety disorders.

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.

Nociception assessment with videopupillometry in deeply sedated intensive care patients: Discriminative and criterion validations.

BACKGROUND: Nociceptive assessment in deeply sedated patients is challenging. Validated instruments are lacking for this unresponsive population. Videopupillometry is a promising tool but has not been established in intensive care settings. AIM/OBJECTIVE: To test the discriminate validity of pupillary dilation reflex (PDR) between non-noxious and noxious procedures for assessing nociception in non-neurological intensive care unit (ICU) patients and to test the criterion validity of pupil dilation using recommended PDR cut-off points to determine nociception. METHODS: A single-centre prospective observational study was conducted in medical-surgical ICU patients. Two independent investigators performed videopupillometer measurements during a non-noxious and a noxious procedure, once a day (up to 7 days), when the patient remained deeply sedated (Richmond Agitation-Sedation Scale score: -5 or -4). The non-noxious procedures consisted of a gentle touch on each shoulder and the noxious procedures were endotracheal suctioning or turning onto the side. Bivariable and multivariable general linear mixed models were used to account for multiple measurements in same patients. Sensitivity and specificity, and areas under the curve of the receiver operating characteristic curve were calculated. RESULTS: Sixty patients were included, and 305 sets of 3 measurements (before, during, and after), were performed. PDR was higher during noxious procedures than before (mean difference between noxious and non-noxious procedures = 31.66%). After testing all variables of patient and stimulation characteristics in bivariable models, age and noxious procedures were kept in the multivariable model. Adjusting for age, noxious procedures (coefficient = -15.14 (95% confidence interval = -20.17 to -15.52, p < 0.001) remained the only predictive factor for higher pupil change. Testing recommended cut-offs, a PDR of >12% showed a sensitivity of 65%, and a specificity of 94% for nociception prediction, with an area under the receiver operating curve of 0.828 (95% confidence interval = 0.779-0.877). CONCLUSIONS: In conclusion, PDR is a potentially appropriate measure to assess nociception in deeply sedated ICU patients, and we suggest considering its utility in daily practices. REGISTRATION: This study was not preregistered in a clinical registry. TWEETABLE ABSTRACT: Pupillometry may help clinicians to assess nociception in deeply sedated ICU patients.

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.

Longitudinal changes in objective accommodative response, pupil size and spherical aberration: A case study.

PURPOSE: Previous transverse and a handful of longitudinal studies have shown that the slope of the static accommodation response/stimulus curve declines as complete presbyopia is approached. Changes in pupillary miosis and ocular spherical aberration (SA) are also evident. This study further investigated longitudinal changes in the relationships between the monocular static accommodative response, pupil diameter and SA of a single adult. METHODS: A wavefront analysing system, the Complete Ophthalmic Analysis System, was used in conjunction with a Badal optometer to allow continuous recording of the aberration structure of the dominant eye in a low myope for a range of accommodative demands (-0.83 to 7.63 D) over a period of 17 years until the age of 50. Monocular accommodative response was calculated as the equivalent refraction minimising wavefront error. The associated longitudinal changes in pupil size and SA with accommodation were also recorded. RESULTS: A decrease in accommodation response with age was found at almost all target vergences, with the changes being greatest for higher vergences. In addition, although absolute pupil diameter decreased with age, the rate of change in pupil diameter with accommodative stimulus remained approximately constant with age. Pupil constriction occurred for near stimuli even in full presbyopia. SA changed linearly with the accommodation response at all ages. CONCLUSIONS: The objective amplitude of accommodation declined linearly with age as complete presbyopia was approached, while the slope of the response/stimulus curve also fell. It was hypothesised that the retinal image blur associated with the larger lags of accommodation at higher accommodative stimuli was reduced by pupil constriction and the resulting lower levels of SA.

Emotional response in babies' pupil contagion.

In this study, it was investigated whether an emotional response would occur in pupil contagion by using skin conductance response (SCR) in 5- and 6-month-old infants. In the experiment, emotional responses to pupil diameter change (dilating/constricting) between the face and eyes regions were compared by using pupil diameter response and SCR. The results showed that pupil diameter responses to pupil diameter changes did not differ between face and eyes regions. The emotional response indicated by the SCR significantly increased when participants looked at dilating pupils of face stimuli compared with when participants looked at constricted pupils of face stimuli. In addition, we found a significant correlation between SCR and pupil dilation in the face. This means that pupil diameter expansion significantly increases emotional response in pupil dilation of the face region.

Bilateral tonic pupil during a migraine attack: a case report / Pupila tônica bilateral durante crise de enxaqueca: relato de caso

INTRODUCTION:Tonic pupil or Adie's pupil occurs due to parasympathetic denervation, and it is characterized by mydriasis with little or no response to light, with pupillary contraction to accommodation. It is caused by eye pathologies, such as infections, trauma, neoplasms, inflammatory diseases, and systemic diseases with autonomic dysfunction. Few cases have been reported of bilateral tonic pupils associated with migraine attacks. CASE REPORT: Our aimed to describe the case of a young female patient with a history of chronic migraine without aura, who presented acutely with bilateral pupillary mydriasis during a migraine attack, characterized as tonic pupil, and to discuss the possible causes of mydriasis during a migraine attack.

INTRODUÇÃO: A pupila tônica ou pupila de Adie ocorre devido à denervação parassimpática e é caracterizada por midríase com pouca ou nenhuma resposta à luz, com contração pupilar à acomodação. É causada por patologias oculares, como infecções, traumas, neoplasias, doenças inflamatórias e doenças sistêmicas com disfunção autonômica. Poucos casos foram relatados de pupilas tônicas bilaterais associadas a crises de enxaqueca. RELATO DE CASO: Nosso objetivo foi descrever o caso de uma paciente jovem, com história de enxaqueca crônica sem aura, que apresentou agudamente midríase pupilar bilateral durante uma crise de enxaqueca, caracterizada como pupila tônica, e discutir as possíveis causas da midríase durante uma crise de enxaqueca. ataque de enxaqueca.