Caffeine is a widely used drug that broadly affects human cognition and brain function. Caffeine acts as an antagonist to the adenosine receptors in the brain. Previous anecdotal reports have also linked caffeine intake with changes in pupil diameter. By modifying the retinal irradiance, pupil diameter modulates all ocular light exposure relevant for visual (i.e., perception, detection and discrimination of visual stimuli) and non-visual (i.e., circadian) functions. To date, the extent of the influence of caffeine on pupillary outcomes, including pupil diameter, has not been examined in a systematic review. We implemented a systematic review laid out in a pre-registered protocol following PRISMA-P guidelines. We only included original research articles written in English reporting studies with human participants, in which caffeine was administered, and pupil diameter was measured using objective methods. Using broad search strategies, we consulted various databases (PsycINFO, Medline, Embase, Cochrane Library, bioRxiv and medRxiv) and used the Covidence platform to screen, review and extract data from studies. After importing studies identified through database search (n = 517 imported, n = 46 duplicates), we screened the title and abstracts (n = 471), finding 14 studies meeting our eligibility criteria. After full-text review, we excluded seven studies, leaving only a very modest number of included studies (n = 7). Extraction of information revealed that the existing literature on the effect of caffeine on pupil parameters is very heterogeneous, differing in pupil assessment methods, time of day of caffeine administration, dose, and protocol timing and design. The evidence available in the literature does not provide consistent results but studies rated as valid by quality assessment suggest a small effect of caffeine on pupil parameters. We summarize the numeric results as both differences in absolute pupil diameter and in terms of effect sizes. More studies are needed using modern pupil assessment methods, robust study design, and caffeine dose-response methodology.

Gaze and pupil metrics are used to represent higher cognitive processes in a variety of contexts. One growing area of research is the real-time assessment of workload and corresponding effort in gamified or simulated cognitive and motor tasks, which will be reviewed in this paper. While some measurements are consistent across studies, others vary and are likely dependent on the nature of the effort required by the task and the resulting changes in arousal. Pupil diameter is shown to consistently increase with task effort and arousal; however, the valence of arousal must be considered. In many cases, measures of pupil diameter were sensitive to both excessive and insufficient challenge. Overall, it is evident that gaze and pupil metrics are valuable to assess the cognitive state during gamified and simulated tasks, and further research is indicated regarding their use in clinical populations in rehabilitation to inform optimally engaging interventions.

Pupil dilation has been associated with the effort required to perform various cognitive tasks. At the lexical level, some studies suggest that this neurophysiological measure would provide objective, real-time information during word processing and lexical access. However, due to the scarcity and incipient advancement of this line of research, its applicability, use, and sensitivity are not entirely clear. This scoping review aims to determine the applicability and usefulness of pupillometry in the study of lexical access by providing an up-to-date overview of research in this area. Following the PRISMA protocol, 16 articles were included in this review. The results show that pupillometry is a highly applicable, useful, and sensitive method for assessing lexical skills of word recognition, word retrieval, and semantic activation. Moreover, it easily fits into traditional research paradigms and methods in the field. Because it is a non-invasive, objective, and automated procedure, it can be applied to any population or age group. However, the emerging development of this specific area of research and the methodological diversity observed in the included studies do not yet allow for definitive conclusions in this area, which in turn does not allow for meta-analyses or fully conclusive statements about what the pupil response actually reflects when processing words. Standardized pupillary recording and analysis methods need to be defined to generate more accurate, replicable research designs with more reliable results to strengthen this line of research.

BACKGROUND: Neurodegenerative diseases share retinal abnormalities. Chromatic pupillometry allows in vivo assessment of photoreceptor functional integrity, including melanopsin-expressing retinal ganglion cells. This exploratory meta-analysis assesses retinal photoreceptor functionality in Alzheimer\'s vs. Parkinson\'s disease and conducts an in-depth review of applied pupillometric protocols.
METHODS: Literature reviews on PubMed and Scopus from 1991 to August 2023 identified chromatic pupillometry studies on Alzheimer\'s disease (AD; n = 42 patients from 2 studies) and Parkinson\'s disease (PD; n = 66 from 3 studies). Additionally, a pre-AD study (n = 10) and an isolated REM Sleep Behavior Disorder study (iRBD; n = 10) were found, but their results were not included in the meta-analysis statistics.
RESULTS: Melanopsin-mediated post-illumination pupil response to blue light was not significantly impaired in Alzheimer\'s (weighted mean difference = -1.54, 95% CI: 4.57 to 1.49, z = -1.00, p = 0.319) but was in Parkinson\'s (weighted mean difference = -9.14, 95% CI: 14.19 to -4.08, z = -3.54, p < 0.001). Other pupil light reflex metrics showed no significant differences compared to controls. Studies adhered to international standards of pupillometry with moderate to low bias. All studies used full-field stimulation. Alzheimer\'s studies used direct while Parkinson\'s studies used consensual measurement. Notably, studies did not control for circadian timing and Parkinson\'s patients were on dopaminergic treatment.
CONCLUSIONS: Results affirm chromatic pupillometry as a useful method to assess melanopsin-related retinal cell dysfunction in Parkinson\'s but not in Alzheimer\'s disease. While adhering to international standards, future studies may analyze the effects of local field stimulation, dopaminergic treatment, and longitudinal design to elucidate melanopsin dysfunction in Parkinson\'s disease.

Elaborative affective processing is observed in depression, and pupillary reactivity, a continuous, sensitive, and reliable indicator of physiological arousal and neurocognitive processing, is increasingly utilized in studies of depression-related characteristics. As a first attempt to quantitively summarize existing evidence on depression-related pupillary reactivity alterations, this review and meta-analysis evaluated the direction, magnitude, and specificity of pupillary indices of affective processing towards positively, negatively, and neutrally-valenced stimuli among individuals diagnosed with depression or with elevated risk of depression. Studies on pupillary responses to affective stimuli in the target groups were identified in PsycINFO and PubMed databases. Twenty-two articles met inclusion criteria for the qualitative review and 16 for the quantitative review. Three-level frequentist and Bayesian models were applied to summarize pooled effects from baseline-controlled stimuli-induced average changes in pupillary responses. In general, compared to non-depressed individuals, individuals with depression or elevated risk of depression exhibited higher pupillary reactivity (d =0.15) towards negatively-valenced stimuli during affective processing. Pupillary motility towards negatively-valenced stimuli may be a promising trait-like marker for depression vulnerability.

Pupil dilation functions as a proxy for cognitive effort and can be measured through automated pupillometry. The aim of this scoping review is to examine how individuals with cognitive impairment differ in task-evoked pupillary responses relative to cognitively healthy individuals. A systematic literature search across six databases was conducted to identify studies examining changes in pupillary responses evoked by cognitive tasks comparing patients with dementia to healthy controls. Eight articles met inclusion criteria and were included for review. Differences in task-evoked pupillary response between cognitively impaired and cognitively healthy participants were observed across studies. Pupil dilation is decreased in patients with Alzheimer\'s Disease compared to controls, with no difference observed in patients with mild cognitive impairment. A mild, non-significant trend towards reduced pupil dilation in patients with either Parkinson\'s Disease or Dementia with Lewy Bodies suggests a similar but less pronounced effect than in AD patients. Further research is required to examine the utility of task-evoked pupillary responses as a potential biomarker indexing cognitive decline in individuals transitioning to mild cognitive impairment and/or dementia.

The association between intraoperative nociception and increased patient\'s morbidity is well established. However, hemodynamic parameters, such as heart rate and blood pressure, may result in an inadequate monitor of nociception during surgery. Over the last two decades, different devices have been marketed to \"reliably\" detect intraoperative nociception. Since the direct measure of nociception is impractical during surgery, these monitors measures nociception surrogates such as sympathetic and parasympathetic nervous systems responses (heart rate variability, pupillometry, skin conductance), electroencephalographic changes, and muscular reflex arc. Each monitor carries its own advantages and disadvantages. The manuscript aims to give an overview of the most up-to-date information available in the literature on current nociceptor monitors available in clinical practice, with particular focus on their applications in pediatrics.

We carried out a systematic review and meta-analysis to investigate the effects of stimulant and non-stimulant medications on autonomic functioning in people with ADHD (PROSPERO: CRD42020212439). We searched (9th August 2021) PsycInfo, MEDLINE, EMBASE, Web of Science and The Cochrane Library, for randomised and non-randomised studies reporting indices of autonomic activity, (electrodermal, pupillometry and cardiac), pre- and post-medication exposure in people meeting DSM/ICD criteria for ADHD. In the narrative syntheses, we included 5 electrodermal studies, 1 pupillometry study and 57 studies investigating heart rate and blood pressure. In the meta-analyses, 29 studies were included on blood pressure and 32 on heart rate. Administration of stimulants, and to a lesser degree, non-stimulants increased heart rate and blood pressure in people with ADHD. Similarly, an upregulation of arousal, reflected in increased electrodermal activity and pupil diameter was observed following stimulant use. Yet, the methodological diversity of studies presented in this review reinforces the need for more standardised and rigorous research to fully understand the relationship between arousal, medication, and behaviour in ADHD.

Background and objectives: This study aims to evaluate the usefulness of the quantitative pupillary light reflex as a prognostic tool for neurological outcomes in post-cardiac arrest patients treated with targeted temperature management (TTM). Material and Methods: We systematically searched MEDLINE, EMBASE, and the Cochrane Library (search date: 9 July 2021) for studies on post-cardiac arrest patients treated with TTM that had measured the percent constriction of pupillary light reflex (%PLR) with quantitative pupillometry as well as assessed the neurological outcome. For an assessment of the methodological quality of the included studies, two authors utilized the prognosis study tool independently. Results: A total of 618 patients from four studies were included in this study. Standardized mean differences (SMDs) were calculated to compare patients with good or poor neurological outcomes. A higher %PLR measured at 0-24 h after hospital admission was related to good neurological outcomes at 3 months in post-cardiac arrest patients treated with TTM (SMD 0.87; 95% confidence interval 0.70-1.05; I2 = 0%). A higher %PLR amplitude measured at 24-48 h after hospital admission was also associated with a good neurological outcome at 3 months in post-cardiac arrest patients treated with TTM, but with high heterogeneity (standardized mean difference 0.86; 95% confidence interval 0.40-1.32; I2 = 70%). The evidence supporting these findings was of poor quality. For poor neurological outcome, the prognosis accuracy of %PLR was 9.19 (pooled diagnostic odds ratio, I2 = 0%) and 0.75 (area under the curve). Conclusions: The present meta-analysis could not reveal that change of %PLR was an effective tool in predicting neurological outcomes for post-cardiac arrest patients treated with TTM owing to a paucity of included studies and the poor quality of the evidence.

Since seafarers are known to be exposed to numerous job-related stress factors that can cause fatigue, sleepiness, and disturbed sleep behaviour, the aim of this review was to provide an overview of the subjective and objective measurement methods of these strains. Using a systematic review, 166 studies were identified within the period of January 2010 to December 2020 using the PubMed database. Of the 21 studies selected, 13 used both subjective and objective measurement methods. Six studies used only subjective and two studies only objective methods. For subjective assessment, 12 different questionnaires could be identified as well as activity and sleeping logs. Actigraphy and reaction time tests (RTT) were the most common objective methods. In single cases, electrooculography (EOG), pupillometry and ambulatory polysomnography (PSG) were used. Measurement-related limitations due to vessel-related impacts were less often reported than expected. No restrictions of daily routines on board were described, and only single-measurement disturbances due to ship movements were mentioned. The present literature review reveals that there are various routines to measure fatigue, sleepiness, and sleep behaviour on board. A combination of subjective and objective methods often appears to be beneficial. The frequent use of actigraphy and RTT on board suggests good feasibility and reliable measurements with these methods. The use of ambulatory PSG in maritime-like contexts suggests that this method would also be feasible on board.