Impact of light on task-evoked pupil responses during cognitive tasks.

Light has many non-image-forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non-image-forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. In the present study, we aimed to characterise the task-evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (mean [SD] 24.05 [4.0] years; 14 women) whilst they completed an attentional and an emotional auditory task whilst exposed to repeated 30-40-s blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light (0.16 melanopic equivalent daylight illuminance (EDI) lux) or blue-enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500 K]. For the analysis, 15 and then 14 participants were included in the attentional and emotional tasks, respectively. Generalised linear mixed models showed a significant main effect of light level on the task-evoked pupil responses triggered by the attentional and emotional tasks (p ≤ 0.0001). The impact of light was different for the target versus non-target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. There is a smaller sustained pupil size during brighter light blocks but, a higher light level triggers a stronger task-evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus.

Pupillometry to differentiate idiopathic hypersomnia from narcolepsy type 1.

Idiopathic hypersomnia is poorly diagnosed in the absence of biomarkers to distinguish it from other central hypersomnia subtypes. Given that light plays a main role in the regulation of sleep and wake, we explored the retinal melanopsin-based pupil response in patients with idiopathic hypersomnia and narcolepsy type 1, and healthy subjects. Twenty-seven patients with narcolepsy type 1 (women 59%, 36 ± 11.5 years old), 36 patients with idiopathic hypersomnia (women 83%, 27.2 ± 7.2 years old) with long total sleep time (> 11/24 hr), and 43 controls (women 58%, 30.6 ± 9.3 years old) were included in this study. All underwent a pupillometry protocol to assess pupil diameter, and the relative post-illumination pupil response to assess melanopsin-driven pupil responses in the light non-visual input pathway. Differences between groups were assessed using logistic regressions adjusted on age and sex. We found that patients with narcolepsy type 1 had a smaller baseline pupil diameter as compared with idiopathic hypersomnia and controls (p < 0.05). In addition, both narcolepsy type 1 and idiopathic hypersomnia groups had a smaller relative post-illumination pupil response (respectively, 31.6 ± 13.9% and 33.2 ± 9.9%) as compared with controls (38.7 ± 9.7%), suggesting a reduced melanopsin-mediated pupil response in both types of central hypersomnia (p < 0.01). Both narcolepsy type 1 and idiopathic hypersomnia showed a smaller melanopsin-mediated pupil response, and narcolepsy type 1, unlike idiopathic hypersomnia, also displayed a smaller basal pupil diameter. Importantly, we found that the basal pupil size permitted to well discriminate idiopathic hypersomnia from narcolepsy type 1 with a specificity = 66.67% and a sensitivity = 72.22%. Pupillometry may aid to multi-feature differentiation of central hypersomnia subtypes.

Pupil assessment with a new handheld pupillometer in healthy subjects.

OBJECTIVE: To assess the pupil response with a new handheld pupillometer in healthy subjects. METHODS: Sixty-four eyes of 32 healthy subjects (mean age 21.2 years) were tested. After dark adaptation for 10 min, pupil responses to 1 s red and blue light stimuli at 100 cd/m2 were measured in the order from right to left eyes with a 1 min interval. The initial pupil size (D1, mm), minimum pupil size (D2, mm), and constriction rate (CR, %) were obtained. Intra-examiner reproducibility was examined using the coefficient of variation (CV, %) and the Bland-Altman plot. Inter-examiner consistency was examined using the interclass correlation coefficient (ICC) and the agreements with a conventional device, by Pearson's correlation coefficient (r). RESULTS: The CV of all parameters have high reproducibility in the red (11.0-20.7%) and blue (5.5-12.1%) light stimuli. Bland-Altman plot analysis showed no bias with both light stimuli. "Almost perfect" and "substantial" correlations between the examiners were obtained in the red (ICC = 0.78-0.94) and blue (ICC = 0.71-0.89) light stimuli. "Excellent" and "good" correlations between the devices were obtained, except for the CR parameter in the red (D1: r = 0.90; p < 0.001, D2: 0.72; p < 0.001, and CR: 0.08; p = 0.631, respectively) and blue (D1: r = 0.87; p < 0.001, D2: 0.70; p < 0.001, and CR: 0.19; p = 0.274, respectively) light stimuli. CONCLUSION: The novel pupillometer is useful for assessing pupil response. However, because of their different constructions, the CR values cannot be compared directly between the devices.

Neural responses to sensory novelty with and without conscious access.

Detection of novel stimuli that violate statistical regularities in the sensory scene is of paramount importance for the survival of biological organisms. Event-related potentials, phasic increases in pupil size, and evoked changes in oscillatory power have been proposed as markers of sensory novelty detection. However, how conscious access to novelty modulates these different brain responses is not well understood. Here, we studied the neural responses to sensory novelty in the auditory modality with and without conscious access. We identified individual thresholds for conscious auditory discrimination and presented to our participants sequences of tones, where the last stimulus could be another standard, a subthreshold target or a suprathreshold target. Participants were instructed to report whether the last tone of each sequence was the same or different from those preceding it. Results indicate that attentional orientation to behaviorally relevant stimuli and overt decision-making mechanisms, indexed by the P3 event-related response and reaction times, best predict whether a novel stimulus will be consciously accessed. Theta power and pupil size do not predict conscious access to novelty, but instead reflect information maintenance and unexpected sensory uncertainty. These results highlight the interplay between bottom-up and top-down mechanisms and how the brain weights neural responses to novelty and uncertainty during perception and goal-directed behavior.

Sleep and circadian differences between light and heavy adult alcohol drinkers.

BACKGROUND: Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers. METHODS: Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment. RESULTS: The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94). CONCLUSIONS: These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

Expectation-driven novelty effects in episodic memory.

Novel and unexpected stimuli are often prioritised in memory, given their inherent salience. Nevertheless, not all forms of novelty show such an enhancement effect. Here, we discuss the role expectation plays in modulating the way novelty affects memory processes, circuits, and subsequent performance. We first review independent effects of expectation on memory, and then consider how different types of novelty are characterised by expectation. We argue that different types of novelty defined by expectation implicate differential neurotransmission in memory formation brain regions and may also result in the creation of different types of memory. Contextual novelty, which is unexpected by definition, is often associated with better recollection, supported by dopaminergic-hippocampal interactions. On the other hand, expected stimulus novelty is supported by engagement of medial temporal cortices, as well as the hippocampus, through cholinergic modulation. Furthermore, when expected stimulus novelty results in enhanced memory, it is predominantly driven by familiarity. The literature reviewed here highlights the complexity of novelty-sensitive memory systems, the distinction between types of novelty, and how they are differentially affected by expectancy.

Melanopsin hypersensitivity dominates interictal photophobia in migraine.

PURPOSE: To define the melanopsin and cone luminance retinogeniculate pathway contributions to photophobia in healthy controls and migraineurs. METHODS: Healthy controls and migraineurs were categorized according to the International Classification of Headache Disorders criteria. Photophobia was measured under full-field illumination using electromyography in response to narrowband lights spanning the melanopsin and cone luminance action spectra. Migraineurs were tested during their interictal headache-free period. Melanopsin-mediated post-illumination pupil responses quantified intrinsically photosensitive Retinal Ganglion Cell (ipRGC) function. RESULTS: A model combining the melanopsin and cone luminance action spectra best described photophobia thresholds in controls and migraineurs; melanopsin contributions were ∼1.5× greater than cone luminance. In the illumination range causing photophobia, migraineurs had lower photophobia thresholds (∼0.55 log units; p < 0.001) and higher post-illumination pupil response amplitudes (p = 0.03) than controls. CONCLUSION: Photophobia is driven by melanopsin and cone luminance inputs to the cortex via the retino-thalamocortical pathway. In migraineurs, lower photophobia thresholds reflect hypersensitivity of ipRGC and cone luminance pathways, with the larger and prolonged post-illumination pupil response amplitude indicative of a supranormal melanopsin response. Our findings inform artificial lighting strategies incorporating luminaires with low melanopsin excitation and photopic luminance to limit the lighting conditions leading to photophobia.

Modeling pupil responses to rapid sequential events.

Pupil size is an easily accessible, noninvasive online indicator of various perceptual and cognitive processes. Pupil measurements have the potential to reveal continuous processing dynamics throughout an experimental trial, including anticipatory responses. However, the relatively sluggish (~2 s) response dynamics of pupil dilation make it challenging to connect changes in pupil size to events occurring close together in time. Researchers have used models to link changes in pupil size to specific trial events, but such methods have not been systematically evaluated. Here we developed and evaluated a general linear model (GLM) pipeline that estimates pupillary responses to multiple rapid events within an experimental trial. We evaluated the modeling approach using a sample dataset in which multiple sequential stimuli were presented within 2-s trials. We found: (1) Model fits improved when the pupil impulse response function (PuRF) was fit for each observer. PuRFs varied substantially across individuals but were consistent for each individual. (2) Model fits also improved when pupil responses were not assumed to occur simultaneously with their associated trial events, but could have non-zero latencies. For example, pupil responses could anticipate predictable trial events. (3) Parameter recovery confirmed the validity of the fitting procedures, and we quantified the reliability of the parameter estimates for our sample dataset. (4) A cognitive task manipulation modulated pupil response amplitude. We provide our pupil analysis pipeline as open-source software (Pupil Response Estimation Toolbox: PRET) to facilitate the estimation of pupil responses and the evaluation of the estimates in other datasets.

Transient pupil response is modulated by contrast-based saliency.

The sudden appearance of a novel stimulus in the environment initiates a series of orienting responses that include coordinated shifts of gaze and attention, and also transient changes in pupil size. Although numerous studies have identified a significant effect of stimulus saliency on shifts of gaze and attention, saliency effects on pupil size are less understood. To examine salience-evoked pupil responses, we presented visual, auditory, or audiovisual stimuli while monkeys fixated a central visual spot. Transient pupil dilation was elicited after visual stimulus presentation regardless of target luminance relative to background, and auditory stimuli also evoked similar pupil responses. Importantly, the evoked pupil response was modulated by contrast-based saliency, with faster and larger pupil responses following the presentation of more salient stimuli. The initial transient component of pupil dilation was qualitatively similar to that evoked by weak microstimulation of the midbrain superior colliculus. The pupil responses elicited by audiovisual stimuli were well predicted by a linear summation of each modality response. Together, the results suggest that the transient pupil response, as one component of orienting, is modulated by contrast-based saliency, and the superior colliculus is likely involved in its coordination.

Eyes on Memory: Pupillometry in Encoding and Retrieval.

This review critically examines the contributions of pupillometry to memory research, primarily focusing on its enhancement of our understanding of memory encoding and retrieval mechanisms mainly investigated with the recognition memory paradigm. The evidence supports a close link between pupil response and memory formation, notably influenced by the type of novelty detected. This proposal reconciles inconsistencies in the literature regarding pupil response patterns that may predict successful memory formation, and highlights important implications for encoding mechanisms. The review also discusses the pupil old/new effect and its significance in the context of recollection and in reflecting brain signals related to familiarity or novelty detection. Additionally, the capacity of pupil response to serve as a true memory signal and to distinguish between true and false memories is evaluated. The evidence provides insights into the nature of false memories and offers a novel understanding of the cognitive mechanisms involved in memory distortions. When integrated with rigorous experimental design, pupillometry can significantly refine theoretical models of memory encoding and retrieval. Furthermore, combining pupillometry with neuroimaging and pharmacological interventions is identified as a promising direction for future research.

Oculomotor behaviors in youth with an eating disorder: findings from a video-based eye tracking task.

BACKGROUND: The oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder. METHODS: Female youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined. RESULTS: Youth with an eating disorder (n = 65, Mage = 17.16 ± 3.5 years) were compared to healthy controls (HC; n = 65, Mage = 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R; n = 43) or a bulimic spectrum eating disorder (ED-BP; n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33, p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38, p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554, p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60, p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30, p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63, p = 0.029). CONCLUSIONS: These results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.

Video based eye tracking is a promising method for studying differences between individuals with and without a psychiatric disease of interest. While some studies have explored oculomotor behaviors in individuals with an eating disorder, much remains unknown. The present study investigated saccades (fast eye movements between two points), eye blinks and pupil responses between female youth (aged 10­25 years) with and without an eating disorder during a pro-saccade (looking at a point) and anti-saccade (looking away from a point) eye tracking task. Individuals with an eating disorder made more pro-saccade guesses, had a smaller pupil size and blinked less before a trial started. In individuals with a restrictive type eating disorder (e.g., anorexia nervosa restrictive type), pupil responses may have a relationship with emotional dysregulation (poorly regulated emotional responses). Overall, this study represents an important step towards identifying oculomotor behavior differences in individuals with an eating disorder compared to controls.

Attention Mobilization as a Modulator of Listening Effort: Evidence From Pupillometry.

Listening to speech in noise can require substantial mental effort, even among younger normal-hearing adults. The task-evoked pupil response (TEPR) has been shown to track the increased effort exerted to recognize words or sentences in increasing noise. However, few studies have examined the trajectory of listening effort across longer, more natural, stretches of speech, or the extent to which expectations about upcoming listening difficulty modulate the TEPR. Seventeen younger normal-hearing adults listened to 60-s-long audiobook passages, repeated three times in a row, at two different signal-to-noise ratios (SNRs) while pupil size was recorded. There was a significant interaction between SNR, repetition, and baseline pupil size on sustained listening effort. At lower baseline pupil sizes, potentially reflecting lower attention mobilization, TEPRs were more sustained in the harder SNR condition, particularly when attention mobilization remained low by the third presentation. At intermediate baseline pupil sizes, differences between conditions were largely absent, suggesting these listeners had optimally mobilized their attention for both SNRs. Lastly, at higher baseline pupil sizes, potentially reflecting overmobilization of attention, the effect of SNR was initially reversed for the second and third presentations: participants initially appeared to disengage in the harder SNR condition, resulting in reduced TEPRs that recovered in the second half of the story. Together, these findings suggest that the unfolding of listening effort over time depends critically on the extent to which individuals have successfully mobilized their attention in anticipation of difficult listening conditions.

How the eyes respond to sounds.

Eye movements have been extensively studied with respect to visual stimulation. However, we live in a multisensory world, and how the eyes are driven by other senses has been explored much less. Here, we review the evidence on how audition can trigger and drive different eye responses and which cortical and subcortical neural correlates are involved. We provide an overview on how different types of sounds, from simple tones and noise bursts to spatially localized sounds and complex linguistic stimuli, influence saccades, microsaccades, smooth pursuit, pupil dilation, and eye blinks. The reviewed evidence reveals how the auditory system interacts with the oculomotor system, both behaviorally and neurally, and how this differs from visually driven eye responses. Some evidence points to multisensory interaction, and potential multisensory integration, but the underlying computational and neural mechanisms are still unclear. While there are marked differences in how the eyes respond to auditory compared to visual stimuli, many aspects of auditory-evoked eye responses remain underexplored, and we summarize the key open questions for future research.

Effects of linguistic context and noise type on speech comprehension.

Introduction: Understanding speech in background noise is an effortful endeavor. When acoustic challenges arise, linguistic context may help us fill in perceptual gaps. However, more knowledge is needed regarding how different types of background noise affect our ability to construct meaning from perceptually complex speech input. Additionally, there is limited evidence regarding whether perceptual complexity (e.g., informational masking) and linguistic complexity (e.g., occurrence of contextually incongruous words) interact during processing of speech material that is longer and more complex than a single sentence. Our first research objective was to determine whether comprehension of spoken sentence pairs is impacted by the informational masking from a speech masker. Our second objective was to identify whether there is an interaction between perceptual and linguistic complexity during speech processing. Methods: We used multiple measures including comprehension accuracy, reaction time, and processing effort (as indicated by task-evoked pupil response), making comparisons across three different levels of linguistic complexity in two different noise conditions. Context conditions varied by final word, with each sentence pair ending with an expected exemplar (EE), within-category violation (WV), or between-category violation (BV). Forty young adults with typical hearing performed a speech comprehension in noise task over three visits. Each participant heard sentence pairs presented in either multi-talker babble or spectrally shaped steady-state noise (SSN), with the same noise condition across all three visits. Results: We observed an effect of context but not noise on accuracy. Further, we observed an interaction of noise and context in peak pupil dilation data. Specifically, the context effect was modulated by noise type: context facilitated processing only in the more perceptually complex babble noise condition. Discussion: These findings suggest that when perceptual complexity arises, listeners make use of the linguistic context to facilitate comprehension of speech obscured by background noise. Our results extend existing accounts of speech processing in noise by demonstrating how perceptual and linguistic complexity affect our ability to engage in higher-level processes, such as construction of meaning from speech segments that are longer than a single sentence.

Pupil Size Is Sensitive to Low-Level Stimulus Features, Independent of Arousal-Related Modulation.

Similar to a camera aperture, pupil size adjusts to the surrounding luminance. Unlike a camera, pupil size is additionally modulated both by stimulus properties and by cognitive processes, including attention and arousal, though the interdependence of these factors is unclear. We hypothesized that different stimulus properties interact to jointly modulate pupil size while remaining independent from the impact of arousal. We measured pupil responses from human observers to equiluminant stimuli during a demanding rapid serial visual presentation (RSVP) task at fixation and tested how response amplitude depends on contrast, spatial frequency, and reward level. We found that under constant luminance, unattended stimuli evoke responses that are separable from changes caused by general arousal or attention. We further uncovered a double-dissociation between task-related responses and stimulus-evoked responses, suggesting that different sources of pupil size modulation are independent of one another. Our results shed light on neural pathways underlying pupillary response.

Using Task-Evoked Pupillary Response to Predict Clinical Performance during a Simulation Training.

Training in healthcare skills can be affected by trainees' workload when completing a task. Due to cognitive processing demands being negatively correlated to clinical performance, assessing mental workload through objective measures is crucial. This study aimed to investigate task-evoked changes in pupil size as reliable markers of mental workload and clinical performance. A sample of 49 nursing students participated in a cardiac arrest simulation-based practice. Measurements of cognitive demands (NASA-Task Load Index), physiological parameters (blood pressure, oxygen saturation, and heart rate), and pupil responses (minimum, maximum, and difference diameters) throughout revealed statistically significant differences according to performance scores. The analysis of a multiple regression model produced a statistically significant pattern between pupil diameter differences and heart rate, systolic blood pressure, workload, and performance (R2 = 0.280; F (6, 41) = 2.660; p < 0.028; d = 2.042). Findings suggest that pupil variations are promising markers to complement physiological metrics for predicting mental workload and clinical performance in medical practice.

Chromatic pupillometry isolation and evaluation of intrinsically photosensitive retinal ganglion cell-driven pupillary light response in patients with retinitis pigmentosa.

Purpose: The pupil light response (PLR) is driven by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to isolate ipRGC-driven pupil responses using chromatic pupillometry and to determine the effect of advanced retinitis pigmentosa (RP) on ipRGC function. Methods: A total of 100 eyes from 67 patients with advanced RP and 18 healthy controls (HCs) were included. Patients were divided into groups according to severity of visual impairment: no light perception (NLP, 9 eyes), light perception (LP, 19 eyes), faint form perception (FFP, 34 eyes), or form perception (FP, 38 eyes). Pupil responses to rod-weighted (487 nm, -1 log cd/m2, 1 s), cone-weighted (630 nm, 2 log cd/m2, 1 s), and ipRGC-weighted (487 nm, 2 log cd/m2, 1 s) stimuli were recorded. ipRGC function was evaluated by the postillumination pupil response (PIPR) and three metrics of pupil kinetics: maximal contraction velocity (MCV), contraction duration, and maximum dilation velocity (MDV). Results: We found a slow, sustained PLR response to the ipRGC-weighted stimulus in most patients with NLP (8/9), but these patients had no detectable rod- or cone-driven PLR. The ipRGC-driven PLR had an MCV of 0.269 ± 0.150%/s and contraction duration of 2.562 ± 0.902 s, both of which were significantly lower than those of the rod and cone responses. The PIPRs of the RP groups did not decrease compared with those of the HCs group and were even enhanced in the LP group. At advanced stages, ipRGC responses gradually became the main component of the PLR. Conclusion: Chromatic pupillometry successfully isolated an ipRGC-driven PLR in patients with advanced RP. This PLR remained stable and gradually became the main driver of pupil contraction in more advanced cases of RP. Here, we present baseline data on ipRGC function; we expect these findings to contribute to evaluating and screening candidates for novel therapies.

Chromatic pupillometry for evaluating melanopsin retinal ganglion cell function in Alzheimer's disease and other neurodegenerative disorders: a review.

The evaluation of pupillary light reflex (PLR) by chromatic pupillometry may provide a unique insight into specific photoreceptor functions. Chromatic pupillometry refers to evaluating PLR to different wavelengths and intensities of light in order to differentiate outer/inner retinal photoreceptor contributions to the PLR. Different protocols have been tested and are now established to assess in-vivo PLR contribution mediated by melanopsin retinal ganglion cells (mRGCs). These intrinsically photosensitive photoreceptors modulate the non-image-forming functions of the eye, which are mainly the circadian photoentrainment and PLR, via projections to the hypothalamic suprachiasmatic and olivary pretectal nucleus, respectively. In this context, chromatic pupillometry has been used as an alternative and non-invasive tool to evaluate the mRGC system in several clinical settings, including hereditary optic neuropathies, glaucoma, and neurodegenerative disorders such as Parkinson's disease (PD), idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD), and Alzheimer's disease (AD). The purpose of this article is to review the key steps of chromatic pupillometry protocols for studying in-vivo mRGC-system functionality and provide the main findings of this technique in the research setting on neurodegeneration. mRGC-dependent pupillary responses are short-wavelength sensitive, have a higher threshold of activation, and are much slower and sustained compared with rod- and cone-mediated responses, driving the tonic component of the PLR during exposure to high-irradiance and continuous light stimulus. Thus, mRGCs contribute mainly to the tonic component of the post-illumination pupil response (PIPR) to bright blue light flash that persists after light stimulation is switched off. Given the role of mRGCs in circadian photoentrainment, the use of chromatic pupillometry to perform a functional evaluation of mRGcs may be proposed as an early biomarker of mRGC-dysfunction in neurodegenerative disorders characterized by circadian and/or sleep dysfunction such as AD, PD, and its prodromal phase iRBD. The evaluation by chromatic pupillometry of mRGC-system functionality may lay the groundwork for a new, easily accessible biomarker that can be exploited also as the starting point for future longitudinal cohort studies aimed at stratifying the risk of conversion in these disorders.

Value-driven modulation of visual perception by visual and auditory reward cues: The role of performance-contingent delivery of reward.

Perception is modulated by reward value, an effect elicited not only by stimuli that are predictive of performance-contingent delivery of reward (PC) but also by stimuli that were previously rewarded (PR). PC and PR cues may engage different mechanisms relying on goal-driven versus stimulus-driven prioritization of high value stimuli, respectively. However, these two modes of reward modulation have not been systematically compared against each other. This study employed a behavioral paradigm where participants' visual orientation discrimination was tested in the presence of task-irrelevant visual or auditory reward cues. In the first phase (PC), correct performance led to a high or low monetary reward dependent on the identity of visual or auditory cues. In the subsequent phase (PR), visual or auditory cues were not followed by reward delivery anymore. We hypothesized that PC cues have a stronger modulatory effect on visual discrimination and pupil responses compared to PR cues. We found an overall larger task-evoked pupil dilation in PC compared to PR phase. Whereas PC and PR cues both increased the accuracy of visual discrimination, value-driven acceleration of reaction times (RTs) and pupillary responses only occurred for PC cues. The modulation of pupil size by high reward PC cues was strongly correlated with the modulation of a combined measure of speed and accuracy. These results indicate that although value-driven modulation of perception can occur even when reward delivery is halted, stronger goal-driven control elicited by PC reward cues additionally results in a more efficient balance between accuracy and speed of perceptual choices.

Accommodative response to ocular surface pain.

CLINICAL RELEVANCE: The discovery of an accommodative response to ocular surface stimulation could inform clinicians and patients that optical effects may occur due to ocular discomfort and perhaps an assessment of the accommodative system after carrying out interventions impacting the ocular surface, may be warranted. BACKGROUND: There have been no previous reports evaluating the effect of noxious stimulation on accommodation. Here, the accommodative response of healthy participants after the application of noxious corneal stimulation is characterised. METHODS: A computerised Belmonte pneumatic esthesiometer was used to determine detection thresholds (using ascending method of limits), and to randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps, to the central cornea of 15 healthy subjects. For each suprathreshold stimulus, accommodative and pupil responses were measured with a validated eccentric infrared photorefractor. Quantitative differences in accommodative/pupil response, stimulus modality/intensity and left/right eye were analysed using repeated measures ANOVA. Tukey HSD tests were used for all post hoc analyses. RESULTS: Accommodation increased from baseline as the corneal apical stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA, p < 0.05). At 200% threshold, accommodative response was greater than all stimulus intensities (Tukey HSD, all p < 0.05). There was no difference in pupil response between the stimulation intensities (100%, 150% and 200% threshold). There was no difference in accommodative response between the left and right eye for mechanical (ANOVA, p > 0.05) and chemical stimulation (ANOVA, p > 0.05). CONCLUSION: Noxious stimulation of the cornea seems to produce a dose-dependent increase in the accommodative response in the eyes but not a dose-dependent pupil response.