Real-world uptake of an innovative pupil expander device for cataract surgery: Implementation lessons learnt.

Cataract surgery in the eyes, where the pupil does not dilate despite using eye drops, is fraught with vision-threatening complications. About 11 per cent of eyes undergoing cataract surgery have non-dilating, small pupils. The increasing prevalence of benign prostatic hyperplasia (BPH), hypertension, diabetes and medications used for the same are the contributing factors. The recent Food and Drug Administration (FDA) approval for the use of miotic agents in the treatment of presbyopia will lead to a further rise in the number of non-dilating pupils. While pharmacological agents and other methods have been used, mechanical pupil expander devices are the only fail safe option. However, available devices had a steep learning curve and limitations which made them difficult to use, unpredictable and unsafe. With its patented single plane, hexagonal, notches and flanges design, the US FDA registered B-HEX Pupil Expander (Med Invent Devices Pvt. Ltd., India) overcame these limitations and fulfilled an unmet need. The B-HEX is machinable, rapidly produced, consistent, easy to use, safe, and affordable. Despite such advantages, implementation hurdles have restricted its availability to healthcare systems worldwide. Peer acceptance has been steadily growing, with the B-HEX becoming the market leader in India, as evidenced by numerous publications, videos and papers presented at international conferences and comments from opinion leaders endorsing its use. However, impractical regulatory requirements and resource constraints remain a great impediment to the global distribution of this novel invention. This has denied many patients the benefits of a superior and more affordable option. Though value continues to be added to the B-HEX by maintaining a strong intellectual property portfolio with internationally granted Patents and Trademark, increasing its user base, and garnering support from key opinion leaders, only a collaboration with the right partner will help scale up the global reach and make it a leader in the global market.

Task-evoked pupillary responses as potential biomarkers of mild cognitive impairment.

INTRODUCTION: Eye movement alterations are effective biomarkers for Alzheimer's disease (AD). This study examines task-evoked pupillary responses (TEPRs) as potential biomarkers of the mild cognitive impairment (MCI), the symptomatic stage preceding AD. METHODS: The prospective cohort study included 213 MCI patients and 514 cognitively normal controls (CNs). Participants performed a prosaccade (PS) or antisaccade (AS) task while their eye movements were tracked using a Tobii Pro Spectrum system. RESULTS: The CNs showed unique TEPRs linked to better performance, characterized by larger baselines, greater PS target-onset variability, and smaller AS target-onset variability. Conversely, for MCI patients, better performance was linked to larger AS target-onset sizes. Furthermore, MCI patients displayed reduced dilation during the cue and target-onset periods compared to CNs. DISCUSSION: MCI patients showed altered pupillary response patterns associated with cognitive task performance, highlighting the potential of oculomotor changes as a biomarker for early cognitive decline. Highlights: MCI patients displayed markedly smaller pupil dilation than CNs in response to cue and target stimuli.For MCI patients, larger pupil size upon target appearance during antisaccades correlated with better performance.Faster and more consistent prosaccades were linked to better performance in both groups.For MCI patients, the association between longer AS latencies and better performance was more pronounced than in CNs.Combined analysis of TEPRs and saccade performances in a sizeable cohort strengthens the generalizability of our findings to the broader MCI population.

Idiosyncratic pupil regulation in autistic children.

Recent neuroimaging and eye-tracking studies have suggested that children with autism exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here, we extended this research to pupillometry recordings. We successfully acquired pupillometry recordings from 111 children (74 with autism), 4.5-years-old on average, who viewed three 90 s movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group as well as between each autistic child and all children in the TD group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group or the comparison group. Children with autism exhibited significantly weaker inter-subject correlations than TD children in all comparisons. These differences were independent of previously reported differences in gaze inter-subject correlations and were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. The results demonstrate the utility of measuring the idiosyncrasy of pupil regulation, which can be performed with passive viewing of movies even by young children with co-occurring intellectual disability. These findings reveal that a considerable number of children with autism have significantly less stable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

School health services in the Southern District of Israel-between privatization and nationalization.

BACKGROUND: For decades, Israel's economic policy has favored either outsourcing or privatization of public services, including healthcare, generating an ongoing and prolonged debate of this approach. In 1997 school health services (SHS) for elementary and middle school pupils was outsourced to a sub-contractor firm, reducing budget, but also standards, for nurses and physicians. Consequently, the service has dwindled and was focused more and more on vaccinations. Between 2007 and 2012, under full private contractor delivery, SHS quality diminished substantially, leading to a significant decline in vaccination coverage in the Southern District. In 2012, a decision was made to return SHS to state control. METHODS: This study analyzes the delivery parameters of SHS between the period when the service was operated by a private contractor from 2011to 2/2012, and the subsequent provision of the service directly by Ministry of Health (MoH) between 3/2012 and 2013. We compared the rates of vaccination coverage, screening tests and health education programs. RESULTS: A statistically significant increase in SHS delivery for vaccinations and screening was observed in the Southern District of MoH after the transfer of service from contractor. The increase was variable in different population subgroups, and especially notable in the Bedouin schools of the District, where the MMRV vaccination rose from 19.3% to 96.8%. However, a substantial and significant reduction in health education activities was also noted, overall from 24.9% to 5.0%. CONCLUSIONS: The findings suggest that substantial benefits can be derived from direct provision of SHS by MoH and its regional offices, especially in the areas of reduced accessibility and lower socio-economic status. The case study of SHS in the Southern District of Israel can serve as an important example highlighting the impacts of privatization vs nationalization, with potential implications in other fields. These insights should be integral to future discussions of healthcare service provision.

Distortion of overlapping memories relates to arousal and anxiety.

Everyday experiences often overlap, challenging our ability to maintain distinct episodic memories. One way to resolve such interference is by exaggerating subtle differences between remembered events, a phenomenon known as memory repulsion. Here, we tested whether repulsion is influenced by emotional arousal, when resolving memory interference is perhaps most needed. We adapted an existing paradigm in which participants repeatedly studied object-face associations. Participants studied two different-colored versions of each object: a to-be-tested "target" and its not-to-be-tested "competitor" pair mate. The level of interference between target and competitor pair mates was manipulated by making the object colors either highly similar or less similar, depending on the participant group. To manipulate arousal, the competitor object-face associations were preceded by either a neutral tone or an aversive and arousing burst of white noise. Memory distortion for the color of the target objects was tested after each study round to examine whether memory distortions emerge after learning. We found that participants with greater sound-induced pupil dilations, an index of physiological arousal, showed greater memory attraction of target colors towards highly similar competitor colors. Greater memory attraction was also correlated with greater memory interference in the last round of learning. Additionally, individuals who self-reported higher trait anxiety showed greater memory attraction when one of the overlapping memories was associated with something aversive. Our findings suggest that memories of similar neutral and arousing events may blur together after repeated exposures, especially in individuals who show higher arousal responses and symptoms of anxiety.

A randomized control study on post-operative iris distortion following small-pupil cataract surgery using B-HEX pupil expander versus Malyugin ring.

Background: The aim of the study was to evaluate postoperative pupil distortion following small pupil cataract surgeries performed using B-HEX and Malyugin rings (MR). Methods: A randomized control trial was conducted from June 2020 to June 2023 at a tertiary eye-care hospital. The study consisted of 64 participants for cataract surgery with small pupil. There were two groups, one undergoing surgery with the use of B-HEX pupil expander and other with MR intraoperatively and the rest of the surgery was proceeded as per the convention. Areas of preoperative and postoperative images was calculated, put into an online software and pupil distortion was calculated in percentage. Two-tailed t-test was used to see the difference between the two groups. Results: Mean age at presentation was 70.5 ± 10.12 years. Most common cause for small pupil was tamsulosin therapy. Mean size of small-pupil was 3.0 ± 1.1 mm. With the application of two rings, mean pupillary area preoperatively was 4178.23 ± 1589.46 and postoperatively was 6100.44 ± 2658.28 following the use of MR, respectively and 30,002.93 ± 13,193.40 preoperatively and 37,648.26 ± 15,207.01 postoperatively following the use of B-Hex ring respectively. Comparing baseline area from pupillary area at 1-month follow-up, a significant increase was noted for both the rings. Also, MR caused significantly more pupillary distortion compared to B-HEX ring (p < 0.05). Conclusion: MR causes significantly more pupillary distortion in the postoperative period compared to B-HEX ring. Though, both the rings cause pupillary distortion, these devices expand the surgical area adequately, ease the procedure, decrease risk of complications achieving good functional visual outcomes.

Pupillary responses for social versus non-social stimuli in autism: A systematic review and meta-analysis.

Pupillometry has gained attention as a valuable tool for assessing autonomic nervous system activity and studying phasic changes in pupil size to comprehend underlying neurocognitive mechanisms. However, knowledge regarding pupillary responses to social processing in autism is limited. We conducted a systematic review and meta-analysis, examining research studies on pupil size changes that compare social and non-social stimuli in autism. Electronic searches were performed for articles up to September 2023 and relevant studies were evaluated following PRISMA guidelines. Out of 284 articles screened, 14 studies were eligible for systematic review. The results indicated that non-autistic individuals showed larger pupil size for social compared to non-social stimuli (g = 0.54; 95 % CI [0.25, 0.82]), whereas autistic individuals seemed to exhibit no differences between the two conditions. However, high heterogeneity was observed between studies in autistic populations, compromising interpretability. Despite such limitations, pupillary responses may constitute an objective physiological marker of social processing in autism. This review emphasizes the need for further investigations into pupillary responses in autism across different life stages.

Effects of topical 0.5% tropicamide and 1% atropine on pupil diameter, intraocular pressure, and tear production, in healthy pet rabbits.

OBJECTIVE: To evaluate the effects of topical application of 0.5% tropicamide and 1% atropine on pupil diameter (PD), intraocular pressure (IOP), and tear production (TP) in healthy pet rabbits. ANIMALS STUDIED: Ten healthy client-owned rabbits. PROCEDURES: A prospective, randomized, blinded, crossover study was conducted. Each animal received one drop of 0.5% tropicamide or 1% atropine in a randomly selected eye. PD, IOP, and TP were evaluated before drug instillation and at 0.25 h, 0.5 h, 0.75 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 36 h, 48 h, 60 h, and 72 h post-instillation. Data were analyzed using a paired two-sample repeated measures T-test with Bonferroni correction. RESULTS: In both tropicamide and atropine treated eyes, the mean PD significantly increased from 15 min until 12 h after treatment with a maximum PD at 45 min (+2.7 mm and + 2.4 mm respectively). Following tropicamide and atropine instillation, IOP increased significantly in treated eyes at 45 min (+2.9 mmHg) and 15 min (+5.2 mmHg) respectively, compared to untreated eyes. No significant effects were found on TP, in both tropicamide and atropine treated eyes at any time. No effects were observed in the untreated eyes on any of the parameters evaluated for both drugs. CONCLUSIONS: Topical treatment with 0.5% tropicamide and 1% atropine induced mydriasis in healthy pet rabbits and could be considered as effective options when mydriatic/cycloplegic drugs are required.

Experimental Method for Identifying Regions of Use of a Progressive Power Lens Using an Eye-Tracker: Validation Study.

Power distribution of progressive power lenses provides usable regions based on power distribution analysis. However, recent studies demonstrated that these regions are not always used for certain tasks as predicted. This work determines the concordance between the actual region of lens use and compares it with the theoretically located regions. The pupil position of 26 subjects was recorded using an eye-tracking system (Tobii-Pro-Glasses 3) at distance and near-reading tasks while wearing a general use progressive power lens. Subjects were asked to read aloud a text showed on a screen placed at 5.25 m and 37 cm while looking though the central and lateral regions of the lens. The pupil position was projected onto the back surface of the lens to obtain the actual region of use for each fixation. Results showed that the actual region of use matched with the theoretically located. On average, the concordance between the actual and theoretical regions of use was 85% for a distance-reading task and 73% for a near-reading task. In conclusion, the proposed method effectively located the actual regions of the lens used, revealing how users' posture affects lens usage. This insight enables the design of more customized progressive lenses based on the areas used during vision-based tasks.

Dynamic interactions of physiological systems during competitive gaming: insights from network physiology - case report.

This study investigates the dynamic interactions between physiological systems during competitive gaming, utilizing a Network Physiology approach. By examining the physiological responses of a gamer with attention-deficit/hyperactivity disorder playing a real-time strategy game, we explore the relationships and temporal lag effects between pupil dilation, skin temperature, and heart rate. Our findings highlight the interconnectedness of these physiological systems and demonstrate how different physiological states are associated with unique patterns of network interactions. The study employs the concept of Time Delay Stability towards a deeper understanding of the complex dynamics involved. This research contributes to the growing field of Network Physiology by offering new insights into the physiological underpinnings of competitive gaming, potentially informing targeted training and recovery protocols for eSports athletes.

Pupillary dilation response to the auditory food words in adolescents with obesity without binge eating disorder.

Childhood obesity is a growing global public health problem. Studies suggest that environmental cues contribute to developing and maintaining obesity. We aimed to evaluate pupillary changes to auditory food words vs. nonfood words and to conduct a dynamic temporal analysis of pupil size changes in adolescents with obesity without binge eating disorder by comparing healthy-weight adolescents. In this study, a total of 63 adolescents aged 12-18 years (n = 32, obesity group (OG); n = 31, control group (CG)) were included. In an auditory paradigm, participants were presented with a series of high and low-calorie food and nonfood words. A binocular remote eye-tracking device was used to measure pupil diameter. Generalized additive mixed models (GAMMs) were used for dynamic temporal analysis of pupillometry data. The results of GAMM analysis indicated that CG had larger pupil dilation than the OG while listening to auditory food words. CG had larger pupil dilation in food words than in nonfood words. However, the OG had a similar pupillary response in food and nonfood words. Pupil dilation response to higher-calorie foods was extended over the later stages of the time period (after 2000 ms) in the OG. In summary, our findings indicated that individuals with obesity had lower pupil dilation to auditory food words compared to normal-weight peers. Adolescents with obesity had prolonged pupillary dilation in higher calories of food words. The individual psychological factors affecting the dynamic changes of pupil responses to food cues in adolescents with obesity should be examined in further studies.

Analysis of the optical performance of intraocular lenses using profilometric measurements.

PURPOSE: The aim of this study was to develop a methodology, based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls). The "Modulation Transfer Function through-object" (MTF through-object) based on vergence object displacement was calculated for different pupil sizes and pseudophakic eyes. Tilt and decentration were also analysed in a realistic cornea eye model. METHODS: For comparison between the different IOLs, an optical quality criterion based on a minimum value the MTF through-object and the recognition of simulated vision optotypes was introduced. Five IOLs were used in this study: Tecnis Eyhance, Mini Well, Tecnis Symfony, Tecnis Synergy and RayOne EMV. RESULTS: The technique was validated with previous methodologies. A general narrowing of the through-object MTF curve compared to the through-focus MTF curve was shown, resulting in greater distances between near and intermediate points and less depth of field around the far peak. The comparison between the IOLs showed that variations in corneal aberrations, pupil size and decentration caused relevant changes in IOL performance. A decrease of the SA produced a hypermetropic shift of the far focus between + 0.3 D and + 0.4 D. Most of IOLs worsen the optical quality as pupil size increased, even the MTF through-object shape changed. Decentration was an important factor in IOL implantation, causing a significant change in MTF through-object shape in most of IOLs. CONCLUSIONS: This study highlights the need to evaluate pre-operative patients for corneal aberrations and pupillary size to have the best optical success after cataract surgery in multifocal or extended depth of focus IOLs. KEY MESSAGES: What is known MTF(Modulation Transfer Function) through-focus curves (calculated in image space by moving the detector plane) can be obtained from optical bench assembly or from commercial devices. Recently, some studies proposed to characterize the lens surface design based on the profilometric measurements What is new A novel methodology based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls) was shown. The "Modulation Transfer Function through-object" based on vergence object displacement was introduced in order to analyse five premium IOLs. MTF through-object curve is more appropriate for studying clinical behaviour, as it provides further near and intermediate points distances and lower depth of focus around far peak compare to MTF through-focus curves. The optical behaviour of the five IOLs can vary considerably depending on the eye model and pupil size. The effect of tilt and decentration on the MTF through-object the IOLs was analysed.

Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution.

PURPOSE: Evaluate safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), an alpha-1 antagonist, in reversal of pharmacologically induced mydriasis. DESIGN: Two Phase 3, multicenter, placebo-controlled, randomized, double-masked clinical trials in healthy subjects. SUBJECTS: 553 healthy 12 to 80 year old subjects were randomized 1:1 (MIRA-2) and 2:1 (MIRA-3) to receive either POS or placebo eye drops OU. METHODS: Subjects received POS or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide). MAIN OUTCOME MEASURES: Primary endpoint was percent of subjects returning to ≤0.2 mm greater than baseline pupil diameter in study eye at 90 minutes after POS administration. Safety measures included treatment-emergent adverse events (TEAEs) and tolerability measures, including conjunctival hyperemia. RESULTS: In MIRA-2, 185 subjects were randomized to treatment with placebo (94) or POS (91). In MIRA-3, 368 subjects were randomized to treatment with placebo (124) or POS (244). A statistically significant greater percentage of subjects treated with POS had study eyes that showed reversal of mydriasis at 90 minutes (primary endpoint) compared with the placebo treatment (48.9% vs 6.6% for MIRA-2; p<0.0001 and 58% VS 6% for MIRA-3; p<0.0001) and as early as 60 minutes (24.5% vs 5.5% for MIRA-2; p<0.0003 and 42% VS 2% for MIRA-3; p<0.0001). Between 28 to 34% of placebo-treated subjects had not returned to baseline PD at 24 hours following pharmacological dilation compared to 8 to 11% treated with POS (p<0.0001). CONCLUSION: POS treatment had a rapid onset in reducing PD within 60- to 90-minutes, with a statistically significant time savings of 3 to 4 hours to return to baseline PD compared to placebo. One or 2 drops of POS rapidly reversed mydriasis in all subjects regardless of mydriatic agent or iris color. More subjects receiving POS reported a perceived benefit in the resolution of visual symptoms caused by pharmacologically induced mydriasis compared to placebo, with statistically significant differences noted as early as 1 hour. The safety profile was favorable, with the most common adverse effects being mild transient conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%).

Short-term effects of ophthalmic topical 0.01% atropine on the ocular surface, pupil size, and subsequent subjective quality of vision in young myopic Chinese adults.

Background: Daily use of low concentrations of atropine is recommended for children undergoing myopia control therapy. While the benefits of controlling myopia progression have been confirmed, the potential unwanted side effects on the ocular surface, pupil size, and quality of vision following the administration of 0.01% atropine have not been investigated. Objective: This single-arm, self-control study aimed to investigate the short-term effects of 0.01% atropine topical eye drop (He Eye Hospital Co., Ltd., Shenyang, China) on pupil size and subjective quality of vision in participants with myopia. Each 3 mL vial of eye drops contains atropine (0.01%), sodium chloride (0.9%), and benzalkonium chloride (0.005%) in an aqueous solution. Methods: Thirty-three adults (66 eyes) were recruited for the study. The mean age of the participants recruited for this study was 24.91 ± 3.36 years. This study is registered with Clinical Trials.gov (NCT06071260). Assessments were performed at baseline and 10 h, 14 h, and 18 h following the administration of 0.01% topical atropine drop (TAD). Mesopic pupil diameter (MPD), photopic pupil diameter (PPD), higher order aberration (HOA), non-invasive tear breakup time (NITBUT), tear meniscus height (TMH), tear film lipid layer (TFLL), and Redness score (RS). Subjective assessments included the quality of vision (QoV) and the ocular surface disease index (OSDI) questionnaires. Results: Following the use of 0.01% atropine, PPD significantly increased at all the time points (p < 0.001); MPD increased significantly at 10 h and 14 h (p < 0.001 and p < 0.05, respectively). A decrease in TMH and an increase in the OSDI questionnaire scores were observed up to 10 and 14 h, respectively, after using atropine (p < 0.001). Glare (p = 0.004 at 10 h and p = 0.003 at 14 h), blurred vision (p < 0.0001 at 10 h and p = 0.035 at 14 h), and focusing difficulties (p < 0.0001 at 10 h and p < 0.0001 at 14 h) were significantly higher at both 10 h and 14 h after using atropine. No significant changes were observed in the HOA, NITBUT, and RS scores (all p > 0.05) at all time points. Conclusion: Decreased TMH, dry eye symptoms, and visual symptoms will likely persist overnight but often diminish within 18 h after using 0.01% atropine eye drops.

Microsaccades Tracking by Secondary Speckle Pattern Analysis.

Here we propose a not pupil-dependent microsaccades tracking technique and a novel detection method. We present a proof of concept for detecting microsaccades using a non-contact laser-based photonic system recording and processing the temporal changes of speckle patterns scattered from an eye sclera. The data, simultaneously recorded by the speckle-based tracker (SBT) and the video-based eye tracker (Eyelink), was analyzed by the frequently used detection method of Engbert and Kliegl (E&K) and by advanced machine learning detection (MLD) techniques. We detected 93% of microsaccades in the SBT data out of microsaccades detected in the Eyelink data with the E&K method. By utilizing MLD, a precision of 86% was achieved. The findings of our study demonstrate a potential improvement in measuring tiny eye movements, such as microsaccades, using speckle-based eye tracking and, thus, an alternative to video-based eye tracking for detecting microsaccades.

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.

Strategic stabilization of arousal boosts sustained attention.

Arousal and motivation interact to profoundly influence behavior. For example, experience tells us that we have some capacity to control our arousal when appropriately motivated, such as staying awake while driving a motor vehicle. However, little is known about how arousal and motivation jointly influence decision computations, including if and how animals, such as rodents, adapt their arousal state to their needs. Here, we developed and show results from an auditory, feature-based, sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply tailored signal-detection theoretic, hazard function, and accumulation-to-bound modeling approaches in a large cohort of mice. We find that pupil-linked arousal and task utility both have major impacts on multiple aspects of task performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate and optimal level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and in diseases such as attention-deficit/hyperactivity disorder.

Blink-induced changes in pupil dynamics are consistent and heritable.

Pupil size and blink rates are heritable but the extent to which they interact with one another has not been properly investigated. Though changes in pupil size due to eye blinks have been reported, they are considered a pupillary artifact. In this study we used the HCP 7T fMRI dataset with resting state eye-tracking data obtained in monozygous and dizygous twins to assess their heritability and their interactions. For this purpose, we characterized the pupil dilation (positive peak) and constriction (negative peak) that followed blink events, which we describe as blink-induced pupillary response (BIPR). We show that the BIPR is highly consistent with a positive dilatory peak (D-peak) around 500ms and a negative constricting peak (C-peak) around 1s. These patterns were reproducible within- and between- subjects across two time points and differed by vigilance state (vigilant versus drowsy). By comparing BIPR between monozygous and dizygous twins we show that BIPR have a heritable component with significant additive genetic (A) and environmental (E) factors dominating the structural equation models, particularly in the time-domain for both D- and C-peaks and amplitude domain for the C-peak. (a2 between 42-49%). Blink duration, pupil size and blink rate were also found to be highly heritable (a2 up to 62% for pupil size). Our study documents an association between BIPR and wakefulness and indicates that BIPR should not be treated as a coincidental artefact, but part of a larger oculomotor system that we label here as Oculomotor Adaptive System, OAS, that is genetically determined.

Evaluation of 0.1% and 1% atropine eyedrops in cats: A comparative study of tolerance, stability, and efficacy.

OBJECTIVE: Investigate the tolerance, stability, and efficacy of topical 0.1% and 1% atropine in cats. PROCEDURES: Six cats underwent two trials separated by a 2-week washout period. One drop of artificial tears was placed in one randomly selected eye (control), and one drop of either 0.1% atropine (Trial I) or 1% atropine (Trial II) was placed in the other eye. Immediate adverse effects were recorded for severity (0-3) and duration (seconds). Horizontal pupil diameter (HPD), pupillary light reflexes (PLRs), intraocular pressure (IOP), Schirmer tear test-1 (STT-1), and heart rate (HR) were monitored at baseline then 8 h post-administration. PLRs were assessed for a total of 72 h. Stability was assessed weekly for 1 month in room temperature and refrigerated conditions, evaluating solution clarity, pH, and drug concentrations. RESULTS: Adverse effects had a significantly lower severity score and shorter duration with 0.1% versus 1% atropine (severity 1.2 ± 0.4 vs. 2.5 ± 0.5, p = .010; duration 107.5 ± 53.3 vs. 293.3 ± 106.5 s, p = .009). HPD was significantly greater than baseline measurements as early as 40 min for both atropine formulations. Pupils were non-responsive for a significantly shorter duration with 0.1% versus 1% atropine (median 7 h vs. 47.5 h, p = .031). Compared with control eyes, IOP was significantly elevated by 1% atropine (p = .021) but not 0.1% atropine (p = .502). No significant differences were noted in STT-1 and HR measurements. Both solutions were stable in room temperature and refrigerated conditions for 1 month. CONCLUSIONS: Diluted 0.1% atropine was stable and better tolerated by cats, offering a potential alternative to feline patients that experience adverse effects from topical 1% atropine.