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A relative afferent pupillary defect (RAPD) is a characteristic clinical sign of optic neuritis (ON). Here, we systematically evaluated ultrasound pupillometry (UP) for the detection of an RAPD in patients with ON, including a comparison with infrared video pupillometry (IVP), the gold standard for objective pupillometry. We enrolled 40 patients with acute (n = 9) or past (n = 31) ON (ON+), 31 patients with multiple sclerosis (MS) without prior ON, and 50 healthy controls (HC) in a cross-sectional observational study. Examinations comprised the swinging flashlight test, B-mode UP, IVP, autorefraction to assess the best-corrected visual acuity, optical coherence tomography to determine peripapillary retinal nerve fiber layer thickness, and the 51-item National Eye Institute-Visual Function Questionnaire to determine the vision-related quality of life. While UP and IVP measurements of pupil diameter (PD) at rest correlated in ON+ eyes (n = 52, r = 0.56, 95% CI: 0.35; 0.72) and in HC eyes (n = 100, r = 0.60, 95% CI: 0.47; 0.72), PD at rest was smaller in UP than in IVP measurements (difference, mean (SD) ON+ eyes: 0.44 (0.87) mm, HC eyes: 0.69 (0.80) mm). RAPD assessment by UP sharply discriminated acute ON eyes (n = 9) and HC eyes (n = 100, AUC = 1, 95%CI: 1; 1). UP detected an RAPD in 5/31 (16%) patients with MS without prior ON who had not exhibited an RAPD during the swinging flashlight test. In ON+ eyes (n = 52), UP showed stronger correlations with visual acuity (r = 0.66, 95% CI: 0.50; 0.78) and vision-related quality of life (r = 0.47, 95% CI: 0.24; 0.66) than IVP (r = 0.52, 95% CI: 0.36; 0.67 and r = 0.27, 95% CI: 0.03; 0.51). B-mode UP allows for objective detection and quantification of an RAPD with performance characteristics similar to IVP. RAPD assessment by UP may detect subclinical optic nerve damage in patients with MS. We propose a standardized protocol for RAPD detection by UP that can be used in routine clinical evaluation of patients with ON or other optic neuropathies.

The rapid pupillary constriction to an abrupt light stimulus is signaled through an oligosynaptic neural pathway that dominates over other supranuclear influences on pupillary movement. A pupillometric recording of the pupil light reflex shows the steep change in pupil size from baseline to maximal constriction. However, when the pupil is recorded in darkness in the phase after light stimulation or in response to non-light stimuli like a sudden noise or cognitive activity, pupil size changes are small and slow. In such cases, pre-processing of pupil recordings to reduce the noise due to intrusion of various artifactual and non-evoked pupillary movements is particularly important but may be time-consuming. To address the paucity of automated tools for pupil light reflex analysis in pupillometry, we aimed to develop a software for automated, user-guided pupillometric data analysis. We identified two types of commonly observed artifacts on pupil recordings. We designed a software, called PupilMetrics, which imports and displays raw pupil data, detects and removes these two types of artifacts, and quantifies outcome measures like pupil size, response time, maximal contraction amplitude and PIPR. The right pupil of 29 healthy adults was recorded using a Neurolight pupillometer (IDMed, Marseilles) in response to 9 different light stimuli. Data analysis of the total 261 pupil responses were performed manually or automatically using PupilMetrics. High correlation was observed between PupilMetrics and manual analysis outcome measures across all stimuli (average R 2  = 0.9891 and p  < 0.0001) with a near 1-to-1 correspondence (Beta = 0.9940). PupilMetrics reduced the total analysis time from 30 h to under 1 h. PupilMetrics offers a time-efficient alternative to manual processing and delivers comparable results. Such software can facilitate standardization of pupillometry for clinical and research uses.

If a mental image is a rerepresentation of a perception, then properties such as luminance or brightness should also be conjured up in the image. We monitored pupil diameters with an infrared eye tracker while participants first saw and then generated mental images of shapes that varied in luminance or complexity, while looking at an empty gray background. Participants also imagined familiar scenarios (e.g., a \"sunny sky\" or a \"dark room\") while looking at the same neutral screen. In all experiments, participants' eye pupils dilated or constricted, respectively, in response to dark and bright imagined objects and scenarios. Shape complexity increased mental effort and pupillary sizes independently of shapes' luminance. Because the participants were unable to voluntarily constrict their eyes' pupils, the observed pupillary adjustments to imaginary light present a strong case for accounts of mental imagery as a process based on brain states similar to those that arise during perception.

In the Zone argues that challenge is an essential element of true learning, without which there can be no progress. It brings together supportive materials to encourage teachers to reflect on their present practice, take sensible risks with their teaching, and understand the importance of enjoyment and engagement for both teachers and pupils.At a time when test and examination results still dominate the educational landscape, there is a need to focus on, and support teachers with, the real meaning and purpose of learning. In the Zone concerns itself with important aspects of learning that are not always prominent in government policy and legislation. In particular, it argues that challenge is an essential element of true learning, without which there can be no progress. It brings together supportive materials aimed at encouraging teachers to reflect on their present practice, take sensible risks with their teaching, and understand the importance of enjoyment and engagement for both teachers and pupils. Importantly, the book is fully up to date with the new Ofsted Education Inspection Framework and current thinking around positive pupil mental health.\"In the Zone is a concise and accessible book focused on children's learning and how, as a teacher, we can maximise this, both at school and beyond...It is hard to strike the right balance and the author helps with this by offering questions or tasks at the end of each chapter providing structured reflection and prompts to relate the content to personal practice and experience. Furthermore the author's use of a wide range of research, opinions and visual aids alongside real life examples was thought provoking. Therefore the book is ideal as a point of reference if you want to try something new or want to be reminded of personal key motivators for becoming a teacher.\" Isabelle Gulliver, University of Buckingham  

Background Elevated intracranial pressure (ICP) is frequent after traumatic brain injury (TBI) and may cause abnormal pupillary reactivity, which in turn is associated with a worse prognosis. Using automated infrared pupillometry, we examined the relationship between the Neurological Pupil index (NPi) and invasive ICP in patients with severe TBI. Methods This was an observational cohort of consecutive subjects with severe TBI (Glasgow Coma Scale [GCS] < 9 with abnormal lesions on head CT) who underwent parenchymal ICP monitoring and repeated NPi assessment with the NPi-200® pupillometer. We examined NPi trends over time (four consecutive measurements over intervals of 6 h) prior to sustained elevated ICP > 20 mmHg. We further analyzed the relationship of cumulative abnormal NPi burden (%NPi values < 3 during total ICP monitoring time) with intracranial hypertension (ICHT)—categorized as refractory (ICHT-r; requiring surgical decompression) vs. non-refractory (ICHT-nr; responsive to medical therapy)—and with the 6-month Glasgow Outcome Score (GOS). Results A total of 54 patients were studied (mean age 54 ± 21 years, 74% with focal injuries on CT), of whom 32 (59%) had ICHT. Among subjects with ICHT, episodes of sustained elevated ICP ( n  = 43, 172 matched ICP-NPi samples; baseline ICP [T − 6 h ] 14 ± 5 mmHg vs. ICPmax [T 0 h ] 30 ± 9 mmHg) were associated with a concomitant decrease of the NPi (baseline 4.2 ± 0.5 vs. 2.8 ± 1.6, p  < 0.0001 ANOVA for repeated measures). Abnormal NPi values were more frequent in patients with ICHT-r ( n  = 17; 38 [3–96]% of monitored time vs. 1 [0–9]% in patients with ICHT-nr [ n  = 15] and 0.5 [0–10]% in those without ICHT [ n  = 22]; p  = 0.007) and were associated with an unfavorable 6-month outcome (15 [1–80]% in GOS 1–3 vs. 0 [0–7]% in GOS 4–5 patients; p  = 0.002). Conclusions In a selected cohort of severe TBI patients with abnormal head CT lesions and predominantly focal cerebral injury, elevated ICP episodes correlated with a concomitant decrease of NPi. Sustained abnormal NPi was in turn associated with a more complicated ICP course and worse outcome.

Pupillometry research has experienced an enormous revival in the last two decades. Here we briefly review the surge of recent studies on task-evoked pupil dilation in the context of cognitive control tasks with the primary aim being to evaluate the feasibility of using pupil dilation as an index of effort exertion, rather than task demand or difficulty. Our review shows that across the three cognitive control domains of updating, switching, and inhibition, increases in task demands typically leads to increases in pupil dilation. Studies show a diverging pattern with respect to the relationship between pupil dilation and performance and we show how an effort account of pupil dilation can provide an explanation of these findings. We also discuss future directions to further corroborate this account in the context of recent theories on cognitive control and effort and their potential neurobiological substrates.

Purpose It is purported that caffeine, an autonomic stimulant, affects visual performance. This study sought to assess whether caffeine intake was associated with changes in pupil size and/or amplitude of accommodation. Patients and methods A double-masked, crossover study was conducted in 50 healthy subjects of age range 19 to 25 years. Subjects were randomized to treatments such that subjects consumed either 250 mg caffeine drink or vehicle on separate days. Amplitude of accommodation was measured by the push-up technique, and pupil size using a millimeter ruler fixed to a slit lamp biomicroscope in dim illumination (5 lux). Amplitude of accommodation and pupil size were taken at baseline, and at 30, 60 and 90 min time points post treatment. Repeated measures one-way ANOVA and paired t- test were used in analyzing data. Results Amplitude of accommodation and pupil size after caffeine intake were significantly greater than vehicle ( P <0.001) at each time point. Consumption of the caffeine beverage was associated with significant increases in amplitude of accommodation and pupil size with time ( P <0.001). Amplitude of accommodation rose from 12.4 (±2.2 D) at baseline to 15.8(±2.6 D) at 90 min. Similarly, pupil size increased from 3.4 (±0.4 mm) at baseline to 4.5 (±0.72 mm) at 90 min. Consumption of vehicle was not associated with increase in amplitude of accommodation or pupil size with time. Conclusion Pupil size and accommodation are affected after ingestion of caffeine. This study suggests caffeine may have some influence on visual functions.

Changes in pupil diameter can reflect high-level cognitive signals that depend on central neuromodulatory mechanisms. However, brain mechanisms that adjust pupil size are also exquisitely sensitive to changes in luminance and other events that would be considered a nuisance in cognitive experiments recording pupil size. We implemented a simple auditory experiment involving no changes in visual stimulation. Using finite impulse-response fitting we found pupil responses triggered by different types of events. Among these are pupil responses to auditory events and associated surprise: cognitive effects. However, these cognitive responses were overshadowed by pupil responses associated with blinks and eye movements, both inevitable nuisance factors that lead to changes in effective luminance. Of note, these latter pupil responses were not recording artifacts caused by blinks and eye movements, but endogenous pupil responses that occurred in the wake of these events. Furthermore, we identified slow (tonic) changes in pupil size that differentially influenced faster (phasic) pupil responses. Fitting all pupil responses using gamma functions, we provide accurate characterisations of cognitive and non-cognitive response shapes, and quantify each response's dependence on tonic pupil size. These results allow us to create a set of recommendations for pupil size analysis in cognitive neuroscience, which we have implemented in freely available software.

More than 50 years ago, it was proposed that breathing shapes pupil dynamics. This widespread idea is also the general understanding currently. However, there has been no attempt at synthesizing the progress on this topic since. We therefore conducted a systematic review of the literature on how breathing affects pupil dynamics in humans. We assessed the effect of breathing phase, depth, rate, and route (nose/mouth). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and conducted a systematic search of the scientific literature databases MEDLINE, Web of Science, and PsycInfo in November 2021. Thirty-one studies were included in the final analyses, and their quality was assessed with QualSyst. The study findings were summarized in a descriptive manner, and the strength of the evidence for each parameter was estimated following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The effect of breathing phase on pupil dynamics was rated as “low” (6 studies). The effect of breathing depth and breathing rate (6 and 20 studies respectively) were rated as “very low”. Breathing route was not investigated by any of the included studies. Overall, we show that there is, at best, inconclusive evidence for an effect of breathing on pupil dynamics in humans. Finally, we suggest some possible confounders to be considered, and outstanding questions that need to be addressed, to answer this fundamental question. Trial registration: This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD42022285044.

Since COVID-19 was first reported, different neurological complications have been acknowledged, but their description is constantly evolving. We report a case of concurrent tonic pupil and trochlear nerve palsy in this context. A 62-year-old man reported a 5-day history of binocular vertical diplopia and blurred vision in his left eye, noticing that his left pupil was dilated. He had suffered a flu-like syndrome 2 weeks before. Clinical exam showed a right trochlear nerve palsy and a left mydriatic pupil. MRI, X chest ray, and analytical results were normal. Antibodies for SARS-CoV-2 were positive (low IgM and high IgG titers). Antiganglioside antibodies were negative. A 0.125% pilocarpine test confirmed Adie’s pupil diagnosis. The patient was treated with a tapered prednisone dose with resolution of his diplopia but no change in Adie’s pupil. This is the first case reporting Adie’s pupil as a postinfectious manifestation of COVID-19. An immune-mediated mechanism is presumed.