BACKGROUND: Pupillary unrest in ambient light (PUAL) describes the fluctuation of pupil diameter observed in normal, awake subjects under typical levels of indoor light. PUAL becomes low to absent in young healthy subjects during opioid intoxication. We sought to determine the age-related distribution of PUAL values in a random sample of ambulatory participants.
METHODS: Subjects ≥18 years of age were recruited. All were identified by age range (18-29, 30-49, 50-69, and ≥70), and surveyed for diabetes, beta-blocker use, and prior 24-hour opioid use. Relationship between mean PUAL, age group, comorbidity and opioid use were examined by Kruskal Wallis test, and PUAL and was modeled using stepwise multilevel linear regression, including diabetes, beta blocker use, prior 24-hour opioid use, autonomic dysfunction, and pupil diameter as fixed effects and subject as random effect.
RESULTS: Among 150 subjects, 17 reported diabetes, 12 reported beta-blocker use, 14 reported prior 24-hour opioid use, and 120 reported no comorbid conditions. PUAL declined in higher age categories (by 0.0307, P < 0.001), with diabetes (by 0.0481, P = 0.025), and with beta-blocker use (by 0.0616, P = 0.005). Opioid related PUAL decline was observed, but statistical significance varied by model. Among healthy subjects, no PUAL value fell within range indicating high likelihood of opioid toxicity based on previous data from healthy subjects undergoing opioid infusion.
CONCLUSIONS: PUAL declined in higher age groups, diabetes and beta-blocker use, conditions associated with impaired autonomic function, and with opioid use but significance varied depending on the chosen model.

Proactive interference (PI) occurs when previously learned information impairs memory for more recently learned information. Most PI studies have employed verbal stimuli, while the role of PI in visual working memory (VWM) has had relatively little attention. In the verbal domain, Johansson and colleagues (2018) found that pupil diameter - a real-time neurophysiological index of cognitive effort - reflects the accumulation and resolution of PI. Here we use a novel, naturalistic paradigm to test the behavioral and pupillary correlates of PI resolution for what-was-where item-location bindings in VWM. Importantly, in our paradigm, trials (PI vs. no-PI condition) are mixed in a block, and participants are naïve to the condition until they are tested. This design sidesteps concerns about differences in encoding strategies or generalized effort differences between conditions. Across three experiments (N = 122 total) we assessed PI\'s effect on VWM and whether PI resolution during memory retrieval is associated with greater cognitive effort (as indexed by the phasic, task-evoked pupil response). We found strong support for PI\'s detrimental effect on VWM (even with our spatially distributed stimuli), but no consistent link between interference resolution and effort during memory retrieval (this, even though the pupil was a reliable indicator that higher-performing individuals tried harder during memory encoding). We speculate that when explicit strategies are minimized, and PI resolution relies primarily on implicit processing, the effect may not be sufficient to trigger a robust pupillometric response.

UNASSIGNED: Given the traffic safety and occupational injury prevention implications associated with cannabis impairment, there is a need for objective and validated measures of recent cannabis use. Pupillary light response may offer an approach for detection.
UNASSIGNED: Eighty-four participants (mean age: 32, 42% female) with daily, occasional, and no-use cannabis use histories participated in pupillary light response tests before and after smoking cannabis ad libitum or relaxing for 15 min (no use). The impact of recent cannabis consumption on trajectories of the pupillary light response was modeled using functional data analysis tools. Logistic regression models for detecting recent cannabis use were compared, and average pupil trajectories across cannabis use groups and times since light test administration were estimated.
UNASSIGNED: Models revealed small, significant differences in pupil response to light after cannabis use comparing the occasional use group to the no-use control group, and similar statistically significant differences in pupil response patterns comparing the daily use group to the no-use comparison group. Trajectories of pupillary light response estimated using functional data analysis found that acute cannabis smoking was associated with less initial and sustained pupil constriction compared to no cannabis smoking.
UNASSIGNED: These analyses show the promise of pairing pupillary light response and functional data analysis methods to assess recent cannabis use.

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.

OBJECTIVE: Compensatory mechanisms in heart failure (HF) are triggered to maintain adequate cardiac output. Among them, hyperactivation of the sympathetic nervous system (SNS) is one of the main ones and carries a worse prognosis. The pupillary reflex depends on the SNS, and we can evaluate it through pupillometry. The aim of the study was to compare the differences in pupillary reflex between patients with acute HF and controls and to analyse whether these differences in pupillary reflex may offer a new and easy prognostic factor in such patients.
RESULTS: We prospectively and consecutively included 107 patients admitted with decompensated HF. Quantitative pupillometry was performed with the NeuroOptics pupillometry during the first 24 h after admission and prior to discharge. The results were compared with those of a group of 100 healthy volunteers who also underwent pupillometry. The maximum baseline pupil size (MBPS) and the minimum pupil diameter (MPD) were measured. Patients with decompensated HF have a higher MBPS (3.64 ± 0.81) and higher MPD (2.60 ± 0.58) than HF patients at discharge and in the control group (P-value = 0.01 and 0.01, respectively). Also, HF patients presented an improvement in pupillometric values at discharge [MBPS (3.47 ± 0.79) and MPD (2.51 ± 0.58)] and showed no differences compared with the control group [MBPS (3.34 ± 0.82) and MPD (2.40 ± 0.53)] (P-value = 0.19 and 0.14, respectively). In addition, MBPS provides a good independent predictor of in-hospital and 1 month mortality in patients admitted with HF. Six patients (5.61%) died during hospital admission, and 11 patients (10.2%) died in the first month after discharge. Also, four patients (3.74%) were readmitted within 1 month of discharge. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality through MBPS was 0.823. No patient with an MBPS < 3.7 mm died. The ROC curve for predicting combined mortality or readmission within the first month for MBPS was 0.698.
CONCLUSIONS: Pupillometry may be a new, non-invasive, and simple tool to determine the status of SNS, help in the prognostic stratification of acute HF patients, and improve therapeutic management.

UNASSIGNED: Depressive symptoms have been linked to difficulties in revising established negative beliefs in response to novel positive information. Recent predictive processing accounts have suggested that this bias in belief updating may be related to a blunted processing of positive prediction errors at the neural level. In this proof-of-concept study, pupil dilation in response to unexpected positive emotional information was examined as a psychophysiological marker of an attenuated processing of positive prediction errors associated with depressive symptoms.
UNASSIGNED: Participants (N = 34) completed a modified version of the emotional Bias Against Disconfirmatory Evidence (BADE) task in which scenarios initially suggest negative interpretations that are later either confirmed or disconfirmed by additional information. Pupil dilation in response to the confirmatory and disconfirmatory information was recorded.
UNASSIGNED: Behavioral results showed that depressive symptoms were related to difficulties in revising negative interpretations despite disconfirmatory positive information. The eye tracking results pointed to a reduced pupil response to unexpected positive information among people with elevated depressive symptoms.
UNASSIGNED: Altogether, the present study demonstrates that the adapted emotional BADE task can be appropriate for examining psychophysiological aspects such as changes in pupil size along with behavioral responses. Furthermore, the results suggest that depression may be characterized by deviations in both behavioral (i.e., reduced updating of negative beliefs) and psychophysiological (i.e., decreased pupil dilation) responses to unexpected positive information. Future work should focus on a larger sample including clinically depressed patients to further explore these findings.

BACKGROUND: It is known that subjects with a cochlear implant (CI) need to exert more listening effort to achieve adequate speech recognition compared to normal hearing subjects. One tool for assessing listening effort is pupillometry. The aim of this study is to evaluate the effectiveness of adaptive directional microphones in reducing listening effort for CI recipients.
METHODS: We evaluated listening in noise and listening effort degree (by pupillometry) in eight bimodal subjects with three types of CI microphones and in three sound configurations.
RESULTS: We found a correlation only between sound configurations and listening in noise score (p-value 0.0095). The evaluation of the microphone types shows worse scores in listening in noise with Opti Omni (+3.15 dB SNR) microphone than with Split Dir (+1.89 dB SNR) and Speech Omni (+1.43 dB SNR). No correlation was found between microphones and sound configurations and within the pupillometric data.
CONCLUSIONS: Different types of microphones have different effects on the listening of CI patients. The difference in the orientation of the sound source is a factor that has an impact on the listening effort results. However, the pupillometry measurements do not significantly correlate with the different microphone types.

BACKGROUND: Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.
OBJECTIVE: This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.
METHODS: An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.
RESULTS: Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.
CONCLUSIONS: This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.

UNASSIGNED: In neurologic prognostication of comatose survivors from cardiac arrest, two independent predictors of poor outcome are the loss of the Pupillary light reflex (PLR) and the loss of the N20 response from Somatosensory Evoked potentials (SSEP). The PLR can be quantitatively assessed by pupillometry. Both tests depend on the midbrain, in which a dysfunction reflects a severe hypoxic injury. We reasoned that a certain level of defective PLR would be predictive of a bilaterally absent SSEP N20 response.
UNASSIGNED: Neurological Pupil index (NPi) from the pupillometry and the SSEP N20 response were registered >48 h after cardiac arrest in comatose survivors. Clinical data were retrospectively analyzed. A receiver operating characteristic curve was used to evaluate the capacity of NPi to predict bilaterally absent SSEP N20 response. An NPi threshold value resulting in <5% false positive rate (FPR) for bilaterally absent N20 response was identified.
UNASSIGNED: From February 2020 to August 2022, we included 54 patients out of which 49 had conclusive pupillometry and SSEP examinations. The NPi threshold value with FPR < 5% was 3.4, yielding 36% sensitivity (95% CI 18-55) and significantly discriminated between respective groups with preserved and bilaterally absent N20 response to SSEP (p-value <0.01).
UNASSIGNED: In this limited cohort, NPi < 3.4 in patients remaining comatose >48 hours after cardiac arrest predicted bilateral loss of the SSEP N20 response with a FPR < 5%. If validated in a larger cohort, an NPi threshold may be clinically applied in settings where SSEP is unavailable.

UNASSIGNED: The study investigated how auditory training affects effort exerted by hearing-impaired listeners in speech-in-noise task.
UNASSIGNED: Pupillometry was used to characterise listening effort during a hearing in noise test (HINT) before and after phoneme-in-noise identification training. Half of the study participants completed the training, while the other half formed an active control group.
UNASSIGNED: Twenty 63-to-79 years old experienced hearing-aid users.
UNASSIGNED: Higher peak pupil dilations (PPDs) were obtained at the end of the study compared to the beginning in both groups of the participants. The analysis of pupil dilation in an extended time window revealed, however, that the magnitude of pupillary response increased more in the training than in the control group. The effect of training on effort was observed in pupil responses even when no improvement in HINT was found.
UNASSIGNED: The results demonstrate that using a listening effort metric adds additional insights into the effectiveness of auditory training compared to the situation when only speech-in-noise performance is considered. Trends observed in pupil responses suggested increased effort-both after the training and the placebo intervention-most likely reflecting the effect of the individual\'s motivation.