Jacobi-Fourier phase masks as ophthalmic elements to correct presbyopia.

PURPOSE: Investigations into the correction of presbyopia have considered lens design, clinical implications and the development of objective metrics such as the visual Strehl ratio. This study investigated the Jacobi-Fourier phase mask as an ophthalmic element in the correction of presbyopia. The goal was to develop a contact or intraocular lens whose performance was largely insensitive to changes in pupil diameter. METHODS: Numerical simulations based on Fourier optics were performed to evaluate three different Jacobi-Fourier polynomials, with the aim of providing a range of clear vision (1 Dioptre (D)). Performance was evaluated for three pupil sizes (6, 4 and 2 mm), while polychromatic images were simulated using three different wavelengths (656.3, 587.6 and 486.1 nm). The Neural Transfer function was included in the simulation. To validate the method and results, we used the Visual Strehl combined objective metric (VSCombined) currently used in visual optics. This metric gives more weight to the phase transfer function and is more suitable for non-symmetrical phase functions. RESULTS: Numerical validation showed the suitability of the Jacobi-Fourier phase masks for extending the range of clear vision of presbyopic eyes, providing a visual acuity of at least 0.10 logMAR (6/7.5 Snellen) at all distances between 1 and 6 m. The results show a range of clear vision of 1D was not affected by changes in pupil size, an increase in retinal image contrast accompanied by image artefact reduction by increasing the radial order of the Jacobi-Fourier phase mask and a reduction of wavelength dependence of the retinal images. These results are supported by simulated images and the objective criterion VSCombined. CONCLUSIONS: The use of Jacobi-Fourier phase masks as ophthalmic elements for presbyopic correction show promising results, with a good range of clear vision and reduced dependence on pupil size and chromatic aberration.

No effects of cerebellar transcranial random noise stimulation on cerebellar brain inhibition, visuomotor learning, and pupil diameter.

Cerebellar brain inhibition (CBI) is an inhibitory output from the cerebellum to the primary motor cortex, which is decreased in early motor learning. Transcranial random noise stimulation (tRNS) is a noninvasive brain stimulation to induce brain plastic changes; however, the effects of cerebellar tRNS on CBI and motor learning have not been investigated yet to our knowledge. In this study, whether cerebellar tRNS decreases CBI and improves motor learning was examined, and pupil diameter was measured to examine physiological changes due to the effect of tRNS on motor learning. Thirty-four healthy subjects were assigned to either the cerebellar tRNS group or the Sham group. The subjects performed visuomotor tracking task with ten trials each in the early and late learning stages while receiving the stimulus intervention. CBI and motor evoked potentials were measured before the learning task, after the early learning stage, and after the late learning stage, and pupil diameter was measured during the task. There was no change in CBI in both groups. No group differences in motor learning rates were observed at any learning stages. Pupil diameter was smaller in the late learning stage than in the early learning stage in both groups. The cerebellar tRNS was suggested not to induce changes in CBI and improvement in motor learning, and it did not affect pupil diameter.

Head-mounted eye tracker videos and raw data collected during breathing recognition attempts in simulated cardiac arrest.

This paper presents data collected by Pedrotti et al. (2022, 2024) [1,2], which includes videos captured using a Dikablis head-mounted eye tracker (Ergoneers GmbH, Germany), along with the corresponding raw data. The data collection aimed to assess participants' ability to recognize breathing in a simulated cardiac arrest scenario. Equipped with the eye tracker, participants entered a room where a manikin was positioned on the floor. Their task was to determine if the manikin was breathing and respond accordingly, such as initiating cardiopulmonary resuscitation if the victim was not breathing. Our analysis focused on examining looking time on the manikin's thorax by inspecting the videos. Potential applications of the dataset [3] include identifying fixation and saccades using custom algorithms, analyzing pupil diameter data, and conducting secondary analyses involving participant characteristics like age and gender as independent variables.

Cortical Networks Relating to Arousal Are Differentially Coupled to Neural Activity and Hemodynamics.

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25, respectively, at a time lag of 0 s. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in the prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies >1 Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity.

Using mobile eye tracking to measure cognitive load through gaze behavior during walking in lower limb prosthesis users: A preliminary assessment.

BACKGROUND: Lower limb amputation does not affect only physical and psychological functioning but the use of a prosthetic device can also lead to increased cognitive demands. Measuring cognitive load objectively is challenging, and therefore, most studies use questionnaires that are easy to apply but can suffer from subjective bias. Motivated by this, the present study investigated whether a mobile eye tracker can be used to objectively measure cognitive load by monitoring gaze behavior during a set of motor tasks. METHODS: Five prosthetic users and eight able-bodied controls participated in this study. Eye tracking data and kinematics were recorded during a set of motor tasks (level ground walking, walking on uneven terrain, obstacle avoidance, stairs up and ramp down, as well as ramp up and stairs down) while the participants were asked to focus their gaze on a visual target for as long as possible. Target fixation times and increase in pupil diameters were determined and correlated to subjective ratings of cognitive load. FINDINGS: Overall, target fixation time and pupil diameter showed strong negative and positive correlations, respectively, to the subjective rating of cognitive load in the able-bodied controls (-0.75 and 0.80, respectively). However, the individual correlation strength, and in some cases, even the sign, was different across participants. A similar trend could be observed in prosthetic users. INTERPRETATION: The results of this study showed that a mobile eye tracker may be used to estimate cognitive load in prosthesis users during locomotor tasks. This paves the way to establish a new approach to assessing cognitive load, which is objective and yet practical and simple to administer. Nevertheless, future studies should corroborate these results by comparing them to other objective measures as well as focus on translating the proposed approach outside of a laboratory.

ANOPOW FOR REPLICATED NONSTATIONARY TIME SERIES IN EXPERIMENTS.

We propose a novel analysis of power (ANOPOW) model for analyzing replicated nonstationary time series commonly encountered in experimental studies. Based on a locally stationary ANOPOW Cramér spectral representation, the proposed model can be used to compare the second-order time-varying frequency patterns among different groups of time series and to estimate group effects as functions of both time and frequency. Formulated in a Bayesian framework, independent two-dimensional second-order random walk (RW2D) priors are assumed on each of the time-varying functional effects for flexible and adaptive smoothing. A piecewise stationary approximation of the nonstationary time series is used to obtain localized estimates of time-varying spectra. Posterior distributions of the time-varying functional group effects are then obtained via integrated nested Laplace approximations (INLA) at a low computational cost. The large-sample distribution of local periodograms can be appropriately utilized to improve estimation accuracy since INLA allows modeling of data with various types of distributions. The usefulness of the proposed model is illustrated through two real data applications: analyses of seismic signals and pupil diameter time series in children with attention deficit hyperactivity disorder. Simulation studies, Supplementary Materials (Li, Yue and Bruce, 2023a), and R code (Li, Yue and Bruce, 2023b) for this article are also available.

Comparison of concurrent cognitive load measures during n-back tasks.

The cognitive load experienced by humans is an important factor affecting their performance. Cognitive overload or underload may result in suboptimal human performance and may compromise safety in emerging human-in-the-loop systems. In driving, cognitive overload, due to various secondary tasks, such as texting, results in driver distraction. On the other hand, cognitive underload may result in fatigue. In automated manufacturing systems, a distracted operator may be prone to muscle injuries. Similar outcomes are possible in many other fields of human performance such as aviation, healthcare, and learning environments. The challenge with such human-centred applications is that the cognitive load is not directly measurable. Only the change in cognitive load is measured indirectly through various physiological, behavioural, performance-based and subjective means. A method to objectively assess the performance of such diverse measures of cognitive load is lacking in the literature. In this paper, a performance metric for the comparison of different measures to determine the cognitive workload is proposed in terms of the signal-to-noise ratio. Using this performance metric, several measures of cognitive load, that fall under the four broad groups were compared on the same scale for their ability to measure changes in cognitive load. Using the proposed metrics, the cognitive load measures were compared based on data collected from 28 participants while they underwent n-back tasks of varying difficulty. The results show that the proposed performance evaluation method can be useful to individually assess different measures of cognitive load.

Cortical Zinc Signaling Is Necessary for Changes in Mouse Pupil Diameter That Are Evoked by Background Sounds with Different Contrasts.

Luminance-independent changes in pupil diameter (PD) during wakefulness influence and are influenced by neuromodulatory, neuronal, and behavioral responses. However, it is unclear whether changes in neuromodulatory activity in a specific brain area are necessary for the associated changes in PD or whether some different mechanisms cause parallel fluctuations in both PD and neuromodulation. To answer this question, we simultaneously recorded PD and cortical neuronal activity in male and female mice. Namely, we measured PD and neuronal activity during adaptation to sound contrast, which is a well-described adaptation conserved in many species and brain areas. In the primary auditory cortex (A1), increases in the variability of sound level (contrast) induce a decrease in the slope of the neuronal input-output relationship, neuronal gain, which depends on cortical neuromodulatory zinc signaling. We found a previously unknown modulation of PD by changes in background sensory context: high stimulus contrast sounds evoke larger increases in evoked PD compared with low-contrast sounds. To explore whether these changes in evoked PD are controlled by cortical neuromodulatory zinc signaling, we imaged single-cell neural activity in A1, manipulated zinc signaling in the cortex, and assessed PD in the same awake mouse. We found that cortical synaptic zinc signaling is necessary for increases in PD during high-contrast background sounds compared with low-contrast sounds. This finding advances our knowledge about how cortical neuromodulatory activity affects PD changes and thus advances our understanding of the brain states, circuits, and neuromodulatory mechanisms that can be inferred from pupil size fluctuations.

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.

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.

Change in three-dimensional choroidal vessel network after AR device assisted 1-hour visual task in 2D/3D mode in young healthy subjects.

PURPOSE: The purpose of the study was to investigate the changes of choroidal blood perfusion in different layers and quadrants and its possible related factors after 1 h visual task by augmented reality (AR) device in two-dimensional (2D) and three-dimensional (3D) mode, respectively. METHODS: Thirty healthy subjects aged 22-37 years watched the same video source in 2D and 3D mode separately using AR glasses for 1 h with a one-week interval. Swept-source optical coherence tomography angiography (SS-OCTA) was performed before and immediately after watching to acquire choroidal thickness (ChT), three-dimensional choroidal vascularity index (CVI) of large- and middle-sized choroidal vessels and choriocapillaris flow voids (FV%) at macular and peripapillary area. Near point of accommodation (NPA) and accommodative facility (AF) were examined to evaluate the accommodative ability. Pupil diameters by infrared-automated pupillometer under scotopic, mesopic and photopic condition were also obtained. RESULTS: Compared with pre-visual task, the subfoveal CVI decreased from 0.406 ± 0.097 to 0.360 ± 0.102 after 2D watching (p < 0.001) and to 0.368 ± 0.102 after 3D watching (p = 0.002). Pupil sizes under different illuminance conditions became smaller after both 2D and 3D watching (all p < 0.001). AF increased after both 2D and 3D watching (both p < 0.05). NPA receded in post-3D watching (p = 0.017) while a not significant tendency was observed in post-2D. CONCLUSION: A reduction in subfoveal choroidal blood flow accompanied with pupil constriction was observed immediately after 1 h visual task using AR glasses in 2D and 3D mode. Accommodative facility improved after 2D and 3D watching with AR glasses, whereas decrease in the maximum accommodation power was only found in 3D mode.

Effects of gabapentin on intraocular pressure, tear production and horizontal pupil diameter in New Zealand White rabbits.

BACKGROUND: This study aimed to investigate the effects of gabapentin on various ocular parameters in New Zealand White rabbits. METHODS: A randomised, placebo-controlled crossover study design was employed. Eight New Zealand White rabbits were randomly assigned to receive either oral gabapentin at a dosage of 15 mg/kg or an oral placebo, with a 1-week washout period between treatments. Intraocular pressure, tear production and horizontal pupil diameter were measured at baseline (T0) and at 30, 60, 90, 120, 180, 240 and 360 minutes after drug administration. Physiological and behavioural changes were also recorded for both treatments following drug administration. RESULTS: The administration of gabapentin did not have any significant effects on the ocular parameters measured in this study. However, the rabbits exhibited some muscle relaxation with partially closed eyes during handling, and they were slightly easier to remove from the cage when treated with gabapentin compared to the placebo treatment. LIMITATIONS: In this study, the ocular effects of gabapentin were assessed in only a small number of healthy rabbits. These effects may differ in rabbits with pre-existing eye conditions or in those receiving other medications. CONCLUSIONS: Our findings suggest that gabapentin treatment does not have a significant impact on intraocular pressure, tear production or horizontal pupil diameter in rabbits.

Repeatability and Agreement of Chord Mu between Scheimpflug Tomography and Swept-Source Optical Coherence Tomography.

PURPOSE: To evaluate repeatability and agreement of chord mu between Scheimpflug tomography (Pentacam HR) and sweptsource optical coherence tomography-based optical biometer (IOLMaster 700). METHODS: In this retrospective study, 63 eyes from 33 patients were included. Chord mu, X and Y Cartesian distances between the corneal vertex and the pupil center (Px and Py), and the pupil diameter were compared using two instruments. Repeatability was evaluated using intraclass correlation coefficient (ICC), coefficient of variation (CoV), and within-subject standard deviation (Sw). Interdevice agreement was evaluated using paired t-tests and Bland-Altman plots. RESULTS: Although Sw values for all parameters were similar between the two devices, CoV values of chord mu and pupil diameter were lower, and ICC values of those parameters were higher, in the IOLMaster 700 than in the Pentacam HR. Chord mu and pupil diameter values were higher in IOLMaster 700 than Pentacam HR (p < 0.01). The width of the 95% limit of agreement was wide for all parameters. CONCLUSIONS: IOLMaster 700 showed better repeatability than Pentacam HR in chord mu, Px, Py, and pupil diameter values. Because there were statistically significant differences and a low level of agreement in chord mu and pupil diameter values between the two devices, they cannot be used interchangeably.

The necessity of pretreatment with 0.1% pranoprofen for femtosecond-assisted cataract surgery: A single-center, randomized controlled trial.

Purpose: To explore the effect of the variation of pupil diameter (PD) and intraocular pressure (IOP) induced by femtosecond laser treatment on the subsequent phacoemulsfication and intraocular lens implantation. And whether the application of 0.1% pranoprofen could significantly reduce the miosis and increased IOP caused by femtosecond laser treatment in femtosecond laser-assisted cataract surgery (FLACS). Methods: In this study, patients were pretreated with (trial group) or without (control group) topical 0.1% pranoprofen. The PD and IOP were measured at different time points within 30 â€‹min after the completion of the femtosecond laser treatment. Results: The comparisons of the two groups showed the PD of patients pretreated with 0.1% pranoprofen was significantly larger than that of the control only at 15 â€‹min after FLACS (P â€‹= â€‹0.046), and there was no significant difference in IOP at any time point (P â€‹> â€‹0.05). Neither the ratio of significant miosis (PD â€‹≤ â€‹5 â€‹mm) nor intraocular hypertension (IOP ≥30 â€‹mmHg) was significantly different between the control group (1.72%, 6.67%) and the trial group (1%, 4.17%) (P â€‹> â€‹0.05). Conclusions: The PD and IOP of patients undergoing FLACS showed fluctuations within a small range. The rates of significant miosis and intraocular hypertension are very low, it is safe for surgeons to complete the follow-up procedures within 30 â€‹min after femtosecond laser treatment. Pretreatment with 0.1% pranoprofen exerted a slight, albeit significant prophylactic effect preventing pupil miosis. However, it provided only a limited benefit in patients undergoing FLACS without other complications.

Pupillographic Analysis of COVID-19 Patients: Early and Late Results After Recovery.

Objectives: We aimed to investigate the short- and long-term static and dynamic pupillary responses of patients recovered from coronavirus disease-19 (COVID-19) using quantitative infrared pupillography. Methods: This study included patients who recovered from COVID-19 (Group 1) and age- and gender-matched controls (Group 2). A detailed ophthalmic examination was performed at 1 month and 6 months after the diagnosis of COVID-19. Photopic, mesopic, and scotopic pupil diameters (PDs) were measured using a quantitative infrared pupillography which was integrated into Scheimpflug/Placido photography-based topography system. PDs at 0, 2nd, 4th, and 6th seconds, and average pupil dilation speeds at 2nd, 4th, 6th, and 8th seconds were recorded. Results: Eighty-six eyes of 86 patients (Group 1: n=42; Group 2: n=44) were included. While the mean photopic, mesopic, and scotopic PDs were significantly larger in the COVID-19 group than the control group in the 1st month (p=0.035, p=0.017, p=0.018, respectively), no statistically significant difference was found in the 6th month. Besides, average pupil dilation speeds and PDs at the 0, 2nd, 4th, and 6th seconds were not statistically significantly different between the two groups in the 1st month and 6th month. Conclusion: PDs were significantly larger in COVID-19 patients in all light intensities in the 1st month after COVID-19. However, pupillary dilation was transient, and no significant difference was found in the 6th month. We suggest that the transient pupillary dilation may be secondary to the autonomic nervous system dysfunction and/or optic nerve and visual pathways alterations following COVID-19.

The nonlinearity of pupil diameter fluctuations in an insight task as criteria for detecting children who solve the problem from those who do not.

Insights, characterized by sudden discoveries following unsuccessful problem-solving attempts, are fascinating phenomena. Dynamic systems perspectives argue that insight arises from self-organizing perceptual and motor processes. Entropy and fractal scaling are potential markers for emerging new and effective solutions. This study investigated whether specific features associated with self-organization in dynamical systems can distinguish between individuals who succeed and those who fail in solving insight tasks. To achieve this, we analyzed pupillary diameter fluctuations of children aged 6 to 12 during the 8-coin task, a well-established insight task. The participants were divided into two groups: successful (n = 24) and unsuccessful (n = 43) task completion. Entropy, determinism, recurrence ratio, and the ß scaling exponent were estimated using Recurrence Quantification and Power Spectrum Density analyses. The results indicated that the solver group exhibited more significant uncertainty and lower predictability in pupillary diameter fluctuations before finding the solution. Recurrence Quantification Analysis revealed changes that went unnoticed by mean and standard deviation measures. However, the ß scaling exponent did not differentiate between the two groups. These findings suggest that entropy and determinism in pupillary diameter fluctuations can identify early differences in problem-solving success. Further research is needed to determine the exclusive role of perceptual and motor activity in generating insights and investigate these results' generalizability to other tasks and populations.

Parents regulate arousal while sharing experiences with their child: a study of pupil diameter change responses.

Introduction: Parents provide their children with their first exposures to reciprocal shared experiences, and parental modeling of socio-emotional behaviors and regulatory responses largely influences their child's behavioral and neurological development. Some parental reactions are conscious, while others are non-volitional. This project aimed to explore parent-child pupil dilation change responses during shared interactions, specifically, whether parents' neuro-regulatory responses when sharing experiences with their child are different than responses of children interacting with their parents or children and adult peers sharing with each other. Methods: To test this, four distinct interacting groups were recruited: (1) Parents sharing with their child; (2) Children sharing with their parent; (3) Children sharing with peers; and (4) Adults sharing with peers. All dyads engaged in a computerized shared imagery task, which facilitates communication and mental imagery during a shared experience. During the task, pupil diameter change was recorded as a measure of regulatory response. Results: Findings highlight that parents sharing with their child have lower pupil diameter change than children sharing with their parents (p < 0.01), children sharing with peers (p < 0.01), and adults sharing with peers (p < 0.05), While no differences were seen between children sharing with parents, children sharing with peers or adults sharing with peers. Discussion: Findings deepen the understanding of the neuroscience of parenting, by suggesting that parents, even of older children and adolescents, tend to regulate their arousal when interacting with their child, a response that proves to be unique compared to other dyad types for sharing experiences. Considering this dynamic, findings may direct future parent-led intervention methods to improve the child's socio-emotional development.

A possible contribution of the locus coeruleus to arousal enhancement with mild exercise: evidence from pupillometry and neuromelanin imaging.

Acute mild exercise has been observed to facilitate executive function and memory. A possible underlying mechanism of this is the upregulation of the ascending arousal system, including the catecholaminergic system originating from the locus coeruleus (LC). Prior work indicates that pupil diameter, as an indirect marker of the ascending arousal system, including the LC, increases even with very light-intensity exercise. However, it remains unclear whether the LC directly contributes to exercise-induced pupil-linked arousal. Here, we examined the involvement of the LC in the change in pupil dilation induced by very light-intensity exercise using pupillometry and neuromelanin imaging to assess the LC integrity. A sample of 21 young males performed 10 min of very light-intensity exercise, and we measured changes in the pupil diameters and psychological arousal levels induced by the exercise. Neuromelanin-weighted magnetic resonance imaging scans were also obtained. We observed that pupil diameter and psychological arousal levels increased during very light-intensity exercise, which is consistent with previous findings. Notably, the LC contrast, a marker of LC integrity, predicted the magnitude of pupil dilation and psychological arousal enhancement with exercise. These relationships suggest that the LC-catecholaminergic system is a potential a mechanism for pupil-linked arousal induced by very light-intensity exercise.

Impact of acute psychosocial stress on attentional control in humans. A study of evoked potentials and pupillary response.

Psychosocial stress has increased considerably in our modern lifestyle, affecting global mental health. Deficits in attentional control are cardinal features of stress disorders and pathological anxiety. Studies suggest that changes in the locus coeruleus-norepinephrine system could underlie the effects of stress on top-down attentional control. However, the impact of psychosocial stress on attentional processes and its underlying neural mechanisms are poorly understood. This study aims to investigate the effect of psychosocial stress on attentional processing and brain signatures. Evoked potentials and pupillary activity related to the oddball auditory paradigm were recorded before and after applying the Montreal Imaging Stress Task (MIST). Electrocardiogram (ECG), salivary cortisol, and subjective anxiety/stress levels were measured at different experimental periods. The control group experienced the same physical and cognitive effort but without the psychosocial stress component. The results showed that stressed subjects exhibited decreased P3a and P3b amplitude, pupil phasic response, and correct responses. On the other hand, they displayed an increase in Mismatch Negativity (MMN). N1 amplitude after MIST only decreased in the control group. We found that differences in P3b amplitude between the first and second oddball were significantly correlated with pupillary dilation and salivary cortisol levels. Our results suggest that under social-evaluative threat, basal activity of the coeruleus-norepinephrine system increases, enhancing alertness and decreasing voluntary attentional resources for the cognitive task. These findings contribute to understanding the neurobiological basis of attentional changes in pathologies associated with chronic psychosocial stress.

Crossover Randomized Study of Pharmacologic Effects of Ripasudil-Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine.

INTRODUCTION: Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α2-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine. METHODS: This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics. RESULTS: Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC. CONCLUSION: RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC. TRIAL REGISTRATION: Japan Registry of Clinical Trials; Registration No. jRCT2080225220.