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.

UNASSIGNED: The present study investigated the impact of two different light intensities on the pain-modulated pupillary light response (PLR). Additionally, it aimed to demonstrate parasympathetic and sympathetic influences on PLR parameters in response to pain, as predicted by functional models.
UNASSIGNED: A total of 24 participants were included in a randomized, repeated-measures design. The PLR was measured in response to both dark and bright light stimuli within two test cycles. Pain was induced using the cold pressor test (CPT), which involved immersing participants\' feet in ice water. PLR measurements were taken during baseline and ice-water immersion within each test cycle. The assessed PLR parameters included initial diameter (INIT), latency (LAT), amplitude (AMP), and re-dilation time (ReDIL25). Along with these parameters, heart rate (HR) and pain ratings were also computed and analyzed.
UNASSIGNED: The CPT caused moderate pain in participants, and the resulting PLR parameters were found to be congruent with the expected parasympathetic and sympathetic nervous system activities. Although the luminance of the stimulus did influence PLR parameters, no interaction with pain exposure was found.
UNASSIGNED: The results showed that different aspects of pain experienced by an individual, as modulated through the sympathetic and parasympathetic nervous systems, are visible in their pupillary reactions to light. Notably, within the range used in the current study, light intensity did not significantly affect the pain-related PLR effects.

In this article, we review eye-tracking studies with dogs (Canis familiaris) with a threefold goal; we highlight the achievements in the field of canine perception and cognition using eye tracking, then discuss the challenges that arise in the application of a technology that has been developed in human psychophysics, and finally propose new avenues in dog eye-tracking research. For the first goal, we present studies that investigated dogs\' perception of humans, mainly faces, but also hands, gaze, emotions, communicative signals, goal-directed movements, and social interactions, as well as the perception of animations representing possible and impossible physical processes and animacy cues. We then discuss the present challenges of eye tracking with dogs, like doubtful picture-object equivalence, extensive training, small sample sizes, difficult calibration, and artificial stimuli and settings. We suggest possible improvements and solutions for these problems in order to achieve better stimulus and data quality. Finally, we propose the use of dynamic stimuli, pupillometry, arrival time analyses, mobile eye tracking, and combinations with behavioral and neuroimaging methods to further advance canine research and open up new scientific fields in this highly dynamic branch of comparative cognition.

Pupillometry is used in humans to monitor pain, nociception and analgesia. This single-center, non-randomized, non-blinded intervention trial, evaluated the effect of nose twitching on the pupil size in awake, sedated, and anesthetized horses. Pupil height (H) and length (L) were measured before (Be) and after (Af) nose twitching in fourteen non-painful adult awake horses (T0). The percentage of variation (PSV) was calculated (PSVTn = [(TnAf-TnBe)/TnBe]*100). Measurements were repeated (Tn) after acepromazine (0.04 mg kg-1 IV) (T1), romifidine (0.04 mg kg-1 IV) (T2), morphine (0.1 mg kg-1 IV) (T3), after anesthesia induction with diazepam (0.05 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV), at the time the horse was placed on the operating table (T4) and when the expiratory fraction of sevoflurane was 2% (T5). HAf vs. HBe, LAf vs. LBe as well as PSVH vs. PSVL at each time were compared with a Mann-Whitney Wilcoxon test. The PSVL and PSVH, as well as HBe and LBe over time were compared with the Skillings-Mack test followed by a Wilcoxon test for paired data to make pairwise comparisons (Tn + 1 vs. Tn). In non-sedated horses (T0), the application of the nose twitch induced a significant increase in pupil length (LT0Be: 17.09 [16.05; 19.67] mm versus LT0Af: 19.52 [18.74; 21.40]) mm (p = 0.004). Thirty minutes after acepromazine administration (T1), nose twitching induced a significant increase in pupil length (LT1Be: 16.45 [14.80; 18.66] mm versus LT1Af 18.31 [17.20; 20.52] mm) (p = 0.016) and height (HT1Be: 8.44 [5.68; 12.04] mm versus HT1Af: 11.09 [7.97; 14.3] mm) (p < 0.001). PSVHT1 was significantly greater than PSVLT1 (p = 0.025). PSVH was higher at T1 than at T0 (p = 0.04). It was also significantly higher at T1 than at T2 (p < 0.001). Romifidine induced mydriasis (HT2Be 16.95 [14.73; 18.77] mm versus HT1Be 8.44 [5.68; 12.04] mm) (p < 0,001) (LT2Be 19.66 [18.45; 20.41] mm versus LT1Be 16.45 [14.80; 18.66] mm) (p < 0.001). The results suggest that nose twitching induced a pupillary dilation in the awake horse. This effect was potentiated after the administration of acepromazine but disappeared after the administration of romifidine.

The negative effects of pain are a constant concern in the surgical management of animals, leading to the search for new drugs or more effective analgesic protocols to control this negative emotion. This study aimed to evaluate the nociceptive response of cannabidiol (CBD) alone and in combination with meloxicam using infrared pupillometry in female dogs undergoing elective ovariohysterectomy (OVH) under isoflurane anesthesia. A total of 60 female dogs of different breeds were included. These dogs were randomly assigned to four study groups according to the treatment: Control Group (G0: n = 15) receiving saline solution; group premedicated with meloxicam at a dose of 0.2 mg Kg-1 IV (GMelox: n = 15). Postoperatively this drug was used at 0.1 mg Kg-1 IV every 24 h; the CBD-treated Group (GCBD: n = 15) at a dose of 2 mg Kg-1 orally in the preoperative. Postoperatively was administrated every 12 h; and the Group premedicated with the combination of meloxicam and CBD (GMelox/CBD: n = 15) Meloxicam at a dose of 0.2 mg Kg-1 IV preoperatively, and 0.1 mg Kg-1 IV during the postoperative. CBD at a dose of 2 mg Kg-1 orally in the preoperative, and every 12 h in the postoperative. Treatments were administered for 48 postoperative hours. After OVH, the pupillary neurologic index, pupillary size, minimum diameter (MIN), percentage change, constriction latency (Lat), constriction velocity, and maximum constriction velocity were recorded as pupillometric variables in both eyes during events (E): Baseline (30 min before drug administration), E30 min, E1h, E2h, E3h, E4h, E8h, E12h, E24h, and E48h. The Short-Form of the Glasgow Composite Measure Pain Scale (GCMPS-SF) was used to assess pain during the same events. Overall, it was observed that the pupillometric variables Size, MIN., and Lat. were significantly higher in G0 compared to the other groups during E30 min, E1h, and E2h (p = 0.03), indicating greater pupil dilation in G0 animals. Additionally, no statistically significant differences were observed in GCMPS-SF between GMelox, GCBD, and GMelox/CBD during the postoperative period (p > 0.05). In contrast, the scores were statistically different compared to G0 (p = 0.00001), where all animals in this group received rescue analgesia at 2 h post-surgery. According to pupillometry and scores on the GCMPS-SF scale, it was observed that monotherapy with cannabidiol provides a similar analgesic effect to meloxicam alone or in combination with cannabidiol to manage acute pain in dogs. Similarly, these findings suggest that infrared pupillometry could be a tool for recognizing acute pain in dogs.

UNASSIGNED: Nowadays museums make large use of digital materials (e.g., virtual tours) to attract visitors. Therefore, it is worthwhile investigating which variables affect the engagement with art outside the museum, and whether digital reproductions of artworks are as effective as museum originals in producing a satisfying aesthetic experience.
UNASSIGNED: Here we tested the effectiveness of introducing additional informative materials on the artistic enjoyment of contemporary paintings presented on a computer screen. Naïve observers were exposed to essential and descriptive labels before viewing artworks. We flanked traditional measurement methods - viewing times and questionnaires, with biometric parameters - pupil responses, eye movements, heart rate, and electrodermal activity. The results were then compared to our previous museum study that adopted the same experimental paradigm.
UNASSIGNED: Our behavioral and psychophysiological data lead to a complex pattern of results. As found in the museum setting, providing detailed descriptions decreases complexity, evokes more positive sensations, and induces pupil dilation but does not enhance aesthetic appreciation. These results suggested that informative labels improve understanding and emotions but have a limited impact on the hedonic evaluation of artworks in both contexts. However, other results do not mirror those found in the museum; in the laboratory setting, participants spend a similar amount of time, have a comparable gaze behavior, and their electrodermal activity and heart rate do not change when viewing artworks with different types of labels. The main difference between the lab and museum settings is the shorter time spent viewing digital reproductions vs. real paintings, although subjective ratings (e.g., liking, interest) are comparable.
UNASSIGNED: Overall, this study indicates that the environmental context does impact the aesthetic experience; although, some beneficial effects of introducing additional relevant content in labels accompanying artworks can also be acquainted through digital media outside of the museum.

Maintaining balance comes naturally to healthy people. In subjects with vestibulopathy, even when compensated, and especially if it is bilateral, maintaining balance requires cognitive effort. Pupillometry is an established method of quantifying cognitive effort. Background/Objectives: We hypothesized that pupillometry would be able to capture the increased effort required to maintain posture in subjects with bilateral vestibulopathy in increasingly difficult conditions. Additionally, we hypothesized that the cognitive workload during balance tasks, indexed by pupil size, would decrease with the activation of the BionicVEST cochleo-vestibular implants. Methods: Subjects with a cochleo-vestibular implant as of March 2023 were recruited, excluding those with ophthalmological issues that precluded pupillometry. Pupillometry was performed using a validated modified videonystagmography system. Computed dynamic posturography and a Modified Clinical Test of Sensory Integration on Balance were performed while the pupil was recorded. Tests were first performed after 24 h of deactivating the vestibular component of the implant. Thereafter, it was reactivated, and after 1 h of rest, the tests were repeated. The pupil recording was processed using custom software and the mean relative pupil diameter (MRPD) was calculated. Results: There was an average of 10.7% to 24.2% reduction in MRPD when the vestibular implant was active, with a greater effect seen in tasks of moderate difficulty, and lesser effect when the task was easy or of great difficulty. Conclusions: Despite technical challenges, pupillometry appears to be a promising method of quantifying the cognitive effort required for maintaining posture in subjects with bilateral vestibulopathy before and after vestibular implantation.

Oculomotor palsy with cyclic spasms is an extremely rare condition whose exact pathophysiology remains a mystery. We followed a boy from the onset of symptoms at the age of ten months until 15 years and documented the case with video oculography. In addition, he was diagnosed with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease type 1). Although a pure coincidence cannot be ruled out, it is conceivable that the underlying demyelinating neuropathy of this patient rendered the oculomotor nerve more susceptible to damage.

UNASSIGNED: Incentive salience processes are important for the development and maintenance of addiction. Eye characteristics such as gaze fixation time, pupil diameter, and spontaneous eyeblink rate (EBR) are theorized to reflect incentive salience and may serve as useful biomarkers. However, conventional cue exposure paradigms have limitations that may impede accurate assessment of these markers.
UNASSIGNED: This study sought to evaluate the validity of these eye-tracking metrics as indicators of incentive salience within a virtual reality (VR) environment replicating real-world situations of nicotine and tobacco product (NTP) use.
UNASSIGNED: NTP users from the community were recruited and grouped by NTP use patterns: nondaily (n=33) and daily (n=75) use. Participants underwent the NTP cue VR paradigm and completed measures of nicotine craving, NTP use history, and VR-related assessments. Eye-gaze fixation time (attentional bias) and pupillometry in response to NTP versus control cues and EBR during the active and neutral VR scenes were recorded and analyzed using ANOVA and analysis of covariance models.
UNASSIGNED: Greater subjective craving, as measured by the Tobacco Craving Questionnaire-Short Form, following active versus neutral scenes was observed (F1,106=47.95; P<.001). Greater mean eye-gaze fixation time (F1,106=48.34; P<.001) and pupil diameter (F1,102=5.99; P=.02) in response to NTP versus control cues were also detected. Evidence of NTP use group effects was observed in fixation time and pupillometry analyses, as well as correlations between these metrics, NTP use history, and nicotine craving. No significant associations were observed with EBR.
UNASSIGNED: This study provides additional evidence for attentional bias, as measured via eye-gaze fixation time, and pupillometry as useful biomarkers of incentive salience, and partially supports theories suggesting that incentive salience diminishes as nicotine dependence severity increases.

BACKGROUND: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD.
METHODS: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups.
RESULTS: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes.
CONCLUSIONS: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.