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Objective: Video-based eye tracking was used to investigate saccade, pupil, and blink abnormalities among patients with Huntington's disease (HD) who watched sequences of short videos. HD, an autosomal dominant neurodegenerative disorder resulting from a CAG mutation on chromosome 4, produces motor and cognitive impairments including slow or irregular eye movements, which have been studied using structured tasks., Methods: To explore how HD affects eye movements under instruction free conditions, we assessed 22 HD patients and their age matched controls in a 10-minute video-based free viewing task., Results: Patients with HD experienced a significant reduction in saccade exploration rate following video clip transitions, an increase in pupil reactions to luminance changes after clip transitions, and a significant higher blink rate throughout the task compared to the control group., Conclusions: These results show that HD has a significant impact on how patients visually explore and respond to their environment under unconstrained and ecologically natural conditions., Significance: Eye tracking in HD patients revealed saccadic, pupil, and blink abnormalities in early HD patients, suggestive of brain circuitry abnormalities that probably involve brain stem deficits. Further research should explore the impact of these changes on the quality of life of the patients affected by the disease., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous. While predominant models suggest fear and harm prevention drive compulsions, many patients also experience uncomfortable sensory-based urges ("sensory phenomena") that may be associated with heightened interoceptive sensitivity. Using an urge-to-blink eyeblink suppression paradigm to model sensory-based urges, we previously found that OCD patients as a group had more eyeblink suppression failures and greater activation of sensorimotor-interoceptive regions than controls. However, conventional approaches assuming OCD homogeneity may obscure important within-group variability, impeding precision treatment development. This study investigated the heterogeneity of urge suppression failure in OCD and examined relationships with clinical characteristics and neural activation. Eighty-two patients with OCD and 38 controls underwent an fMRI task presenting 60-s blocks of eyeblink suppression alternating with free-blinking blocks. Latent profile analysis identified OCD subgroups based on number of erroneous blinks during suppression. Subgroups were compared on behavior, clinical characteristics, and brain activation during task. Three patient subgroups were identified. Despite similar overall OCD severity, the subgroup with the most erroneous eyeblinks had the highest sensory phenomena severity, interoceptive sensitivity, and subjective urge intensity. Compared to other subgroups, this subgroup exhibited more neural activity in somatosensory and interoceptive regions during the early phase (first 30 s) of blink suppression and reduced activity in the middle frontal gyrus during the late phase (second 30 s) as the suppression period elapsed. Heterogeneity of urge suppression in OCD was associated with clinical characteristics and brain function. Our results reveal potential treatment targets that could inform personalized medicine., Competing Interests: Declaration of competing interest Dr. K.A. Collins has consulted for MedAvante-ProPhase, and A. Stein- Regulatory Affairs Consulting, Ltd. in the past, and currently serves as a consultant to Cronos Clinical Consulting Services, Inc. and Relmada Therapeutics, Inc. Dr. R.H. Tobe has received research support (through Nathan Kline Institute) from NIH, Roche Pharmaceuticals, Janssen Pharmaceuticals, Axial Therapeutics, and Maplight Pharmaceuticals; and participated in advisory boards for Roche Pharmaceuticals/Genentech - Nathan Kline Institute has received all honoraria for Dr. Tobe's consulting with Roche Pharmaceuticals/Genentech. All other authors report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Recent advancements in infrared sensing technology have made it possible to visualize tear film dynamics in real time, enabling evaluation of tear film quality during blinking. A retrospective clinical evaluation was conducted to explore this by grading videos of the tear film and comparing grading data with dry eye diagnostic results using the OCULUS keratograph (K5M)., Methods: Videos were used to grade patients' tear film perturbations as compared with healthy control subjects. The grading was then correlated with the ocular surface disease index (OSDI) scores, tear film breakup time (TFBUT), tear meniscus height (TMH), corneal staining, redness, and meibography data., Results: Infrared imaging of the ocular surface revealed instantaneous and recurring dynamic characteristics of the tear film, allowing for the differentiation between normal and abnormal tear films. Abnormal features included a complete absence of a spreading tear film, hindered spreading of the tear film after blinking, areas of tear film instability, or a combination of the latter 2. Some of these features show a resemblance to the tear film appearance after fluorescein staining. The grading of these features correlated with TFBUT and, to a lesser extent, with TMH but did not show significant correlation with any other diagnostic data from the K5M. Furthermore, the speed of tear film spreading after blinking showed a positive correlation with TMH., Conclusions: Direct visualization of the tear film across the entire palpebral aperture using infrared sensing offers a noninvasive, reproducible, and rapid method for assessing the health and quality of the tear film., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study evaluated the isolated and combined effects of fear and PPS paradigms on SBR., Method: The prospective study was conducted with healthy participants. After stimulation of the right median nerve at the wrist, bilateral recordings were randomized under the following conditions: First experiment (with the right hand on the chair armrest): i. baseline recordings, ii. while watching fearful facial expressions from the Karolinska Emotional Faces battery (fear), iii. post-watching (post-fear), iv. while watching neutral facial expressions from the same battery (neutral), v. Immediately after viewing (post-neutral). Second experiment (right hand 2 cm away from the right eye, PPS): i. reference condition (PPS), ii. while watching fearful facial expressions (PPS-fear), iii. while watching neutral facial expressions (PPS-neutral). In each condition, SBR latency, area, duration, and amplitudes were measured and compared between conditions., Results: We included 16 participants. SBR could be recorded in 11 (mean age:30.7 ± 5.2, F/M:5/6). First experiment: SBR amplitude was significantly reduced in fear condition (p = 0.008), and SBR area was reduced considerably in fear and post-fear conditions (p = 0.004) compared to the baseline. Second experiment: The SBR area was higher in the PPS (p = 0.009) compared to the baseline and even higher in the fearPPS compared to the PPS (p = 0.038). In neutral or PPS-neutral conditions, the area of the SBR did not change significantly., Conclusion: Fear suppressed SBR, but fear increased SBR when a threat stimulus was present. The findings were unrelated to habituation or attention, indicating cortical-amygdala-bulbar connections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Blinking contributes to the health and protection of the eye and also holds potential in the context of muscle or nerve disorder diagnosis. Traditional methods of classifying eye blinking as open or closed are insufficient, as they do not capture medical-relevant aspects like closure speed, duration, or percentage. The issue could be solved by reliably detecting blinking intervals in high-temporal recordings. Our research demonstrates the reliable detection of blinking events through data-driven analysis of the eye aspect ratio. In an unsupervised manner, we establish an eye state prototype to identify blink intervals and measure inter-eye synchronicity between moments of peak closure. Additionally, our research shows that manually defined prototypes yield comparable results. Our results demonstrate inter-eye synchronicity up to 4.16 ms. We anticipate that medical professionals could utilize our methods to identify or define disease-specific prototypes as potential diagnostic tools.

Spontaneous eye blinks are brief closures of both eyelids. The spontaneous eye blink rate (SEBR) exceeds physiological corneal needs and is modulated by emotions and cognitive states, including vigilance and attention, in humans. In several animal species, the SEBR is modulated by stress and antipredator vigilance, which may limit the loss of visual information due to spontaneous eye closing. Here, we investigated whether the SEBR is modulated by attention in the domestic horse (Equus caballus). Our data supported previous studies indicating a tonic SEBR specific to each individual. We also found that, superimposed on a tonic SEBR, phasic changes were induced by cognitive processing. Attention downmodulated the SEBR, with the magnitude of blink inhibition proportional to the degree of attentional selectivity. On the other hand, reward anticipation upregulated the SEBR. Our data also suggested that horses possess the cognitive property of object permanence: they understand that an object that is no longer in their visual field has not ceased to exist. In conclusion, our results suggested that spontaneous eye blinks in horses are modulated by attentional cognitive processing., (© 2024. The Author(s).)

Purpose: We determined interblink corneal surface-temperature decline and tear-film evaporation rates of localized tear breakup cold regions (LCRs) and localized tear unbroken warm regions (LWRs) of the corneal surface, as well as that of the overall average corneal surface., Methods: Each subject underwent 4 inter-day visits where the interblink corneal surface-temperature history of the right eye was measured using a FLIR A655sc infrared thermographer. Corneal surface temperature history was analyzed to determine the overall, LCR, and LWR temperature-decline rates. Evaporation rates of LCR and LWR regions were determined from the measured LCR and LWR temperature data using the physical model of Dursch et al., Results: Twenty subjects completed the study. Mean (SD) difference of LCR temperature-decline rate was -0.08 (0.07)°C/s faster than LWR (P < 0.0001). Similarly, evaporation rates of LCR and LWR were statistically different (P < 0.0001). At ambient temperature, mean LCR and LWR evaporation rates were 76% and 27% of pure water evaporation flux, respectively. There was no statistically significant difference between the inter-day measured temperature-decline rates and the interblink starting temperature., Conclusions: Significant differences in corneal temperature-decline rate and evaporation rate between LCR and LWR were quantified using infrared thermography. In agreement with literature, LCRs and LWRs correlate directly with fluorescein break-up areas and unbroken tear areas, respectively. Because lipid-evaporation protection is diminished in breakup areas, higher local evaporation rates and faster local cooling rates occur in LCRs relative to LWRs. Our results confirm this phenomenon clinically for the first time.

Purpose: To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC)., Methods: In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups., Results: The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05)., Conclusions: Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction/aims: Paired-pulse stimulation provides clinically useful information regarding sensory inhibition. When supraorbital nerve stimulation is repeated within a short interval, the response to the second stimulation is reduced to varying degrees. This magnitude of change in stimulation response can be monitored by electromyogram (EMG) or by mechanomyogram (MMG) as in this report. MMG has some advantages such as being less time consuming and lacking stimulus artifact. We compared the use of MMG and EMG to validate MMG as an effective method of assessing blink reflex paired-pulse inhibition., Methods: Eight volunteers participated. Participants received electrical stimulation to the supraorbital nerve of each side. A paired-pulse paradigm was employed, varying the conditioning-test interval between 5 and 800 ms. The R1 component of the induced blink reflex was simultaneously recorded by EMG using a pair of electrodes placed on the lower eyelid and by MMG using an accelerometer placed between the electrodes., Results: The correlation coefficient of the R1 amplitude between MMG and EMG of the grand-averaged waveforms was 0.99. The average participant r value was .91 (range .76-.99). Similar analyses were performed for the amplitude variation of the second response relative to the first response. Results correlated well, yielding r values of .97 and .86 for the grand-averaged waveform and the average for each subject., Discussion: The present results demonstrate that MMG could be an alternative to EMG in assessing paired-pulse inhibition of the electrical blink reflex R1 component., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Working memory tasks, such as n-back and arithmetic tasks, are frequently used in studying mental workload. The present study investigated and compared the sensitivity of several physiological measures at three levels of difficulty of n-back and arithmetic tasks. The results showed significant differences in fixation duration and pupil diameter among three task difficulty levels for both n-back and arithmetic tasks. Pupil diameters increase with increasing mental workload, whereas fixation duration decreases. Blink duration and heart rate (HR) were significantly increased as task difficulty increased in the n-back task, while root mean square of successive differences (RMSSD) and standard deviation of R-R intervals (SDNN) were significantly decreased in the arithmetic task. On the other hand, blink rate and Galvanic Skin Response (GSR) were not sensitive enough to assess the differences in task difficulty for both tasks. All significant physiological measures yielded significant differences between low and high task difficulty except for SDNN. Practitioner summary: This study aimed to assess the sensitivity levels of several physiological measures of mental workload in n-back and arithmetic tasks. It showed that pupil diameter was the most sensitive in both tasks. This study also found that most physiological indices are sensitive to an extreme change in task difficulty levels.

Although patients with facial palsy often complain of disturbed eye blinking which may lead to visual impairment, a blinking analysis is not part of routine grading of facial palsy. Twenty minutes of spontaneous eye blinking at rest of 30 patients with facial palsy (6 with acute palsy; 24 patients with facial synkinesis; median age: 58 years, 67% female), and 30 matched healthy probands (median age: 57 years; 67% female) was smart phone video recorded. A custom computer program automatically extracted eye measures and determined the eye closure rate (eye aspect ratio [EAR]), blink frequency, and blink duration. Facial Clinimetric Evaluation (FaCE), Facial Disability Index (FDI) were assessed as patient-reported outcome measures. The minimal EAR, i.e., minimal visible eye surface during blinking, was significantly higher on the paretic side in patients with acute facial palsy than in patients with synkinesis or in healthy controls. The blinking frequency on the affected side was significantly lower in both patient groups compared to healthy controls. Vice versa, blink duration was longer in both patient groups. There was no clear correlation between the blinking values and FaCE and FDI. Blinking parameters are easy to estimate automatically and add a functionally important parameter to facial grading., (© 2024. The Author(s).)

Eye movement during blinking can be a significant artifact in Event-Related Potentials (ERP) analysis. Blinks produce a positive potential in the vertical electrooculogram (VEOG), spreading towards the posterior direction. Two methods are frequently used to suppress VEOGs: linear regression to subtract the VEOG signal from the electroencephalogram (EEG) and Independent Component Analysis (ICA). However, some information is lost in both. The present algorithm (1) statistically identifies the position of VEOGs in the frontopolar channels; (2) performs EEG averaging for each channel, which results in 'blink templates'; (3) subtracts each template from the respective EEG at each VEOG position, only when the linear correlation index between the template and the segment is greater than a chosen threshold L. The signals from twenty subjects were acquired using a behavioral test and were treated using FilterBlink for subsequent ERP analysis. A model was designed to test the method for each subject using twenty copies of the EEG signal from the subject's mid-central channel (with nearly no VEOG) representing the EEG channels and their respective blink templates. At the same 200 equidistant time points (marks), a signal (2.5 sinusoidal cycles at 1050 ms emulating an ERP) was mixed with each model channel and the respective blink template of that channel, between 500 to 1200 ms after each mark. According to the model, VEOGs interfered with both ERPs and the ongoing EEG, mainly on the anterior medial leads, and no significant effect was observed on the mid-central channel (Cz). FilterBlink recovered approximately 90% (Fp1) to 98% (Fz) of the original ERP and EEG signals for L = 0.1. The method reduced the VEOG effect on the EEG after ERP and blink-artifact averaging in analyzing real signals. The method is straightforward and effective for VEOG attenuation without significant distortion in the EEG signal and embedded ERPs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marques Abramov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The study aimed to investigate the factors associated with anterior location of Marx's line in ocular surface and living habits, especially in tear film., Materials and Methods: This cross-sectional study enlisted 483 participants with meibomian gland dysfunction, who were divided into two groups: 160 participants with mild anterior location of Marx's line and 323 participants with moderate-to-severe anterior location. Participants completed a survey of demographic characteristics (sex, age, length of visual terminal use, sleep duration, skin property), and the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires. They also underwent slit-lamp examinations of the lids, and measurements of non-invasive tear break up time, tear meniscus height, fluorescein tear break up time, lipid layer thickness, partial blink rate, lid wiper epitheliopathy, and meibomian gland dropout., Results: The tear meniscus height (mild:0.21(0.18-0.25), moderate-to-severe:0.19(0.16-0.23), p  = 0.004), fluorescein tear break up time(mild:3(2-4),moderate to severe:2(1-3), p  = 0.000), max LLT(mild:87(62-100), moderate-to-severe:99(69-100), p  = 0.04), average LLT(mild:64.5(47.5-96.75), moderate-to-severe:74(53-100), p  = 0.012), min LLT(mild:52(38-75), moderate-to-severe:59(41-85), p  = 0.029) differed significantly between mild and moderate-to-severe anterior location of Marx's line, and associated to the anterior location of Marx's line(r=-0.134, p  = 0.03; r=-0.194, p  = 0.000; r  = 0.093, p  = 0.041; r  = 0.119, p  = 0.009; r  = 0.105, p  = 0.022) However, no statistical significance was observed in the OSDI, SPEED, partial blink rate, non-invasive tear breakup time, lipid layer thickness, meibomian gland dropout and lid wiper epitheliopathy( p  > 0.05). Meanwhile, in the demographic characteristics, statistically significant correlations were associated with skin property( r  = 0.154, p  = 0.001) and sleep duration(r=-0.124, p  = 0.006), but not with age, sex, and the length of visual terminal use ( p  > 0.05)., Conclusions: Lower TMH and shorter TBUT positively correlated with anterior location of the Marx's line, and were risk factors. Meanwhile, participants with oily skin and shorter sleep duration were more likely to exhibit anterior location of Marx's line.

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5-60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable increase in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This increase was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity., (© 2024 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Clinical Relevance: Electronic displays, including laptops, tablets, and smartphones, have dramatically altered the way information is accessed and become significant factors in human daily life. They interfere with the blink rate and increase dry eye symptoms, which lead to more discomfort compared to hard copy while reading., Background: Digital eye strain occurs when an individual suffers from symptoms, or they are exacerbated, while performing a task requiring digital screen viewing. This study assessed the tear film status immediately following reading on a laptop computer screen versus an identical hard copy., Methods: Thirty young adults with normal ocular health and reporting no significant symptoms of dry eye (ocular surface disease index (OSDI) score < 13 and non-invasive tear break-up time (NITBUT) > 10 seconds) read a text as hard copy and on a laptop computer screen for 30 min on separate days in a random sequence in a controlled reading experimental condition. The texts were matched in size and contrast and presented at a viewing distance of 40 cm. The NITBUT and strip meniscometry tube tests were administered at baseline and after reading in both conditions., Results: The median baseline NITBUT decreased from 13.0 s to 10.0 s ( P  < 0.001) after hardcopy reading and to 7.0 ( P  < 0.001) after reading from a laptop computer screen, with a significant difference between the task medium ( P  = 0.001). The baseline strip meniscometry tube results decreased from 6.7 mm to 5.0 mm ( P  < 0.001) after hardcopy reading and to 5.0 mm ( P  < 0.001) after reading from a laptop computer screen, but there was no significant difference with the task medium ( P  = 0.085)., Conclusion: Reading in both conditions led to tear film instability in terms of the tear film quality and quantity. Additionally, the computer screen has a greater impact on the TBUT compared to hardcopy reading, while these two reading mediums had a similar effect on the tear volume.

Although observational fear learning has been implicated in the development of phobic-related fears, studies investigating observational learning of fear of bodily symptoms remain scarce. Therefore, the aim of the present study was to investigate whether fear in response to bodily symptoms can be acquired simply by observing a fearful reaction to provocation of aversive bodily symptoms in others. Forty healthy participants underwent an observational fear conditioning paradigm consisting of two phases. In the first phase, participants observed a demonstrator reacting to an aversive bodily symptom provocation (unconditioned stimulus or US, i.e., labored breathing) paired with one conditioned stimulus (CS+) but not with the other one (CS-, both CSs were geometric symbols presented on a screen the demonstrator was watching). In the second phase, participants were directly presented with the same conditioned stimuli, but in the absence of the US. Our results revealed enhanced conditioned fear responses in the beginning of the second phase to the CS + as compared to CS-, as indexed by greater skin conductance and subjective fear responses, as well as greater potentiation of startle eyeblink responses to the CS + as compared to the ITI. Taken together, these findings implicate that fear of bodily symptoms can be learned through observation of others, that is, without first-hand experience of bodily threat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The sense of agency varies as a function of arousal in negative emotional contexts. As yet, it is unknown whether the same is true for positive affect, and how inter-individual characteristics might predict these effects. Temporal binding, an implicit measure of the sense of agency, was measured in 59 participants before and after watching either an emotionally neutral film clip or a positive film clip with high or low arousal. Analyses included participants' individual differences in subjective affective ratings, physiological arousal (pupillometry, skin conductance, heart rate), striatal dopamine levels via eye blink rates, and psychopathy. Linear mixed models showed that sexual arousal decreased temporal binding whereas calm pleasure had no facilitation effect on binding. Striatal dopamine levels were positively linked whereas subjective and physiological arousal may be negatively associated with binding towards actions. Psychopathic traits reduced the effect of high arousal on binding towards actions. These results provide evidence that individual differences influence the extent to which the temporal binding is affected by high arousing states with positive valence., (© 2024. The Author(s).)

Background: 22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk., Methods: Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers., Results: Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed., Conclusions: Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment., Competing Interests: Declaration of competing interest David Parker: None. Sidney L. Imes: None. Gabrielle Ruban: None. Opal Ousley: None. Brett Henshey: None. Nicholas Massa: None. Elaine Walker: None. Joseph F. Cubells: None. Erica Duncan: None. Dr. Duncan is a full-time attending psychiatrist in the Mental Health Service Line at the Atlanta Veterans Affairs Health Care System, Decatur, GA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Blink reflex (BR) is an oligosynaptic reflex that involves the ophthalmic branch of the trigeminal nerve (TN), ipsilateral main sensory and trigeminospinal nuclei, bilateral facial nuclei, and the facial nerves (FNs). Theoretically, as BR tests the function of both TN and FNs simultaneously, it is an ideal tool for monitoring the status of TN and FNs during skull base surgeries. Nevertheless, it has been used only recently in surgeries as the use of anesthesia limits its use., Methods: For this systematic review, 2 authors input the search terms [(Blink Reflex) AND (Intraoperative Neuromonitoring OR Neuro Intraoperative Monitoring OR Intraoperative OR NIOM OR IONM) AND (skull base surgery OR Facial Nerve OR Trigeminal Nerve OR Microvascular Decompression OR Hemifacial Spasm)] in MEDLINE through its PubMed interface and other search engines. Articles that fulfilled the inclusion and exclusion criteria were obtained and scrutinized., Results: Seven observational articles with a total of 437 participants were included. All 5 studies that described the use of BR in FN surgery noted that intraoperative BR is beneficial, safe, sensitive, specific, and predictive of outcomes, while 2 articles describing patients with trigeminal neuralgia recommended use of BR in microvascular decompression of TN., Conclusions: Intraoperative BR is a sensitive, specific, and safe monitoring technique that has good predictability of facial paresis and paresthesia among patients undergoing MVD for trigeminal neuralgia and primary hemifacial spasm and patients undergoing cerebellopontine angle tumor resection., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Objective: The current study examined the efficacy of the facial corticobulbar motor evoked potentials (FCoMEPs) and blink reflex (BR) on predicting postoperative facial nerve function during cerebellopontine angle (CPA) tumor surgery., Methods: Data from 110 patients who underwent CPA tumor resection with intraoperative FCoMEPs and BR monitoring were retrospectively reviewed. The association between the amplitude reduction ratios of FCoMEPs and BR at the end of surgery and postoperative facial nerve function was determined. Subsequently, the optimal threshold of FCoMEPs and BR for predicting postoperative facial nerve dysfunction were determined by receiver operating characteristic curve analysis., Results: Valid BR was record in 103 of 110 patients, whereas only 43 patients successfully recorded FCoMEP in orbicularis oculi muscle. A reduction over 50.3% in FCoMEP (O. oris) amplitude was identified as a predictor of postoperative facial nerve dysfunction (sensitivity, 77.1%; specificity, 83.6%). BR was another independent predictor of postoperative facial nerve deficit with excellent predictive performance, especially eyelid closure function. Its optimal cut-off value for predicting long-term postoperative eyelid closure dysfunction was was 51.0% (sensitivity, 94.4%; specificity, 94.4%)., Conclusions: BR can compensate for the deficiencies of the FCoMEPs. The combination of BR and FCoMEPs can be used in CPA tumor surgery., Significance: The study first proposed an optimal cut-off value of BR amplitude deterioration (50.0%) for predicting postoperative eyelid closure deficits in patients undergoing CPA tumor surgery., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT)., Methods: This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included., Results: Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA ( P < 0.001) and NIBUTave ( P = 0.010). OSDI was negatively associated with upper RMGA ( r = -0.450, P < 0.001) and NIBUTave ( r = -0.414, P = 0.001), and positively associated with upper MG grade ( r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = -41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave., Conclusions: The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To compare the ocular effects of exposure to a low-humidity environment with and without contact lens (CL) wear using various non-invasive tests., Methods: Fourteen habitual soft CL wearers were exposed to controlled low humidity (5% relative humidity [RH]) in an environmental chamber for 90 min on two separate occasions. First, when wearing their habitual spectacles and then, on a separate visit, when wearing silicone hydrogel CLs that were fitted specifically for this purpose. All participants had adapted to the new CL prior to data collection. Three non-invasive objective measurements were taken at each visit: blinking rate, objective ocular scatter (measured using the objective scatter index) and ocular surface cooling rate (measured using a long-wave infrared thermal camera). At each visit, measurements were taken before the exposure in comfortable environmental conditions (RH: 45%), and after exposure to environmental stress (low humidity, RH: 5%)., Results: CL wearers showed increased blinking rate (p < 0.005) and ocular scatter (p = 0.03) but similar cooling rate of the ocular surface (p = 0.08) when compared with spectacle wear in comfortable environmental conditions. The exposure to low humidity increased the blinking rate significantly with both types of corrections (p = 0.01). Interestingly, ocular scatter (p = 0.96) and cooling rate (p = 0.73) were not significantly different before and after exposure to low humidity. There were no significant two-way interactions between correction and exposure in any of the measurements., Conclusions: CLs significantly increased the blinking rate, which prevented a quick degradation of the tear film integrity as it was refreshed more regularly. It is hypothesised that the increased blinking rate in CL wearers aids in maintaining ocular scatter quality and cooling rate when exposed to a low-humidity environment. These results highlight the importance of blinking in maintaining tear film stability., (© 2024 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: To investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear., Methods: In this pilot investigation, Phase 1 identified asymptomatic (CLDEQ-8 score ≤ 7) and highly symptomatic (CLDEQ-8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL-wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post-hoc testing. The relationship between comfort scores and the clinical parameters was also investigated., Results: Overall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty-five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference -0.04 mm, 95% CI: -0.07, -0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference -9.89, 95% CI: -18.91, -0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = -0.40, 95% CI: -0.63, -0.11) and blink rate (r = -0.31, 95% CI: -0.57, -0.003)., Conclusion: The potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining., (© 2024 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

We report an experiment to investigate the role of the cerebellum and cerebrum in motor learning of timed movements. Eleven healthy human subjects were recruited to perform two experiments, the first was a classical eye-blink conditioning procedure with an auditory tone as conditional stimulus (CS) and vestibular unconditional stimulus (US) in the form of a double head-tap. In the second experiment, subjects were asked to blink voluntarily in synchrony with the double head-tap US preceded by a CS, a form of Ivanov-Smolensky conditioning in which a command or instruction is associated with the US. Electrophysiological recordings were made of extra-ocular EMG and EOG at infra-ocular sites (IO1/2), EEG from over the frontal eye fields (C3'/C4') and from over the posterior fossa over the cerebellum for the electrocerebellogram (ECeG). The behavioural outcomes of the experiments showed weak reflexive conditioning for the first experiment despite the double tap but robust, well-synchronised voluntary conditioning for the second. Voluntary conditioned blinks were larger than the reflex ones. For the voluntary conditioning experiment, a contingent negative variation (CNV) was also present in the EEG leads prior to movement, and modulation of the high-frequency EEG occurred during movement. US-related cerebellar activity was prominent in the high-frequency ECeG for both experiments, while conditioned response-related cerebellar activity was additionally present in the voluntary conditioning experiment. These results demonstrate a role for the cerebellum in voluntary (Ivanov-Smolensky) as well as in reflexive (classical Pavlovian) conditioning., (© 2023. The Author(s).)

Blinking is a motor act characterized by the sequential closing and opening of the eyelids, which is achieved through the reciprocal activation of the orbicularis oculi and levator palpebrae superioris muscles. This stereotyped movement can be triggered reflexively, occur spontaneously, or voluntarily initiated. During each type of blinking, the neural control of the antagonistic interaction between the orbicularis oculi and levator palpebrae superioris muscles is governed by partially overlapping circuits distributed across cortical, subcortical, and brainstem structures. This paper provides a comprehensive overview of the anatomical and physiological foundations underlying the neural control of blinking. We describe the infra-nuclear apparatus, as well as the supra-nuclear control mechanisms, i.e., how cortical, subcortical, and brainstem structures regulate and coordinate the different types of blinking., (Copyright © 2024 International Federation of Clinical Neurophysiology. All rights reserved.)

Objective: Both blinking and walking are altered in Parkinson's disease and both motor outputs have been shown to be linked in healthy subjects. Additionally, studies suggest an involvement of basal ganglia activity and striatal dopamine in blink generation. We investigated the role of the basal ganglia circuitry on spontaneous blinking and if this role is dependent on movement state and striatal dopamine., Methods: We analysed subthalamic nucleus (STN) activity in seven chronically implanted patients for deep brain stimulation (DBS) with respect to blinks and movement state (resting state and unperturbed walking). Neurophysiological recordings were combined with individual molecular brain imaging assessing the dopamine reuptake transporter (DAT) density for the left and right striatum separately., Results: We found a significantly higher blink rate during walking compared to resting. The blink rate during walking positively correlated with the DAT density of the left caudate nucleus. During walking only, spontaneous blinking was followed by an increase in the right STN beta power and a bilateral subthalamic phase reset in the low frequencies. The right STN blink-related beta power modulation correlated negatively with the DAT density of the contralateral putamen. The left STN blink-related beta power correlated with the DAT density of the putamen in the less dopamine-depleted hemisphere. Both correlations were specific to the walking condition and to beta power following a blink., Conclusion: Our findings show that spontaneous blinking is related to striatal dopamine and has a frequency specific deployment in the STN. This correlation depends on the current movement state such as walking., Significance: This work indicates that subcortical activity following a motor event as well as the relationship between dopamine and motor events can be dependent on the motor state. Accordingly, disease related changes in brain activity should be assessed during natural movement., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: Currently, no solution exists to restore natural eyelid kinematics for patients with complete eyelid paralysis due to loss of function of both the levator palpebrae superioris and orbicularis oculi. These rare cases are prone to complications of chronic exposure keratopathy which may lead to corneal blindness. We hypothesized that magnetic force could be used to fully automate eyelid movement in these cases through the use of eyelid-attached magnets and a spectacle-mounted magnet driven by a programmable motor (motorized magnetic levator prosthesis [MMLP])., Methods: To test this hypothesis and establish proof of concept, we performed a finite element analysis (FEA) for a prototype MMLP to check the eyelid-opening force generated by the device and verified the results with experimental measurements in a volunteer with total bidirectional eyelid paralysis. The subject was then fitted with a prototype to check the performance of the device and its success., Results: With MMLP, eye opening was restored to near normal, and blinking was fully automated in close synchrony with the motor-driven polarity reversal, with full closure on the blink. The device was well tolerated, and the participant was pleased with the comfort and performance., Conclusions: FEA simulation results conformed to the experimentally observed trend, further supporting the proof of concept and design parameters. This is the first viable approach in human patients with proof of concept for complete reanimation of a bidirectionally paretic eyelid. Further study is warranted to refine the prototype and determine the feasibility and safety of prolonged use., Translational Relevance: This is first proof of concept for our device for total bidirectional eyelid paralysis.

Purpose: To investigate the relationship between the kinematics of spontaneous blinks and the anterior area of the levator palpebrae superioris muscle in patients with Graves orbitopathy (GO)., Methods: This is a case-control study. The authors measured the margin reflex distance of the upper eyelid (margin reflex distance 1), the kinematics of spontaneous blinks, and the anterior area of levator palpebrae superioris muscle in CT coronal scans of patients with Graves upper eyelid retraction (GO) and a control group. The eye with the greatest margin reflex distance 1 was selected for analysis in each group., Results: A total of 68 participants were included, with 36 in the GO group and 32 in the control group. In the GO group, the mean margin reflex distance 1 measured 6.5 mm, while in the control group, it was 3.9 mm. Almost all parameters related to the closing phase of spontaneous blinking activity, including amplitude, velocity, blinking rate, and interblink time, did not differ between the two groups. However, the effectiveness of the blink's amplitude (ratio of blink amplitude to margin reflex distance 1) and the main sequence (relationship between amplitude and velocity) were significantly reduced in the GO group compared with the control group. The area of the levator palpebrae superioris muscle was significantly larger in GO than in controls, with 71.4% of patients' muscles outside of the maximum range of the controls., Conclusions: In patients with GO, there is a reduction in blinking effectiveness, also known as blink lagophthalmos, which is a factor in the common occurrence of ocular surface symptoms. The increase in velocity with amplitude is also reduced in GO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Objectives : Facial nerve palsy causes blurred vision and ocular discomfort due to deficits in blinking and eye closure. The objective of this study was to determine whether eye-blinks could be elicited by electrical stimulation and whether electrically induced blink would have an effect on the visual acuity and ocular symptoms in patients with acute facial nerve palsy. Methods : The zygomatic branch of the facial nerve of fifteen participants with acute facial nerve palsy was electrically stimulated in order to elicit a blink. In successful cases, the participant proceeded with a two-hour TV watching session in which an electrically induced blink was delivered every 5 seconds. The control condition consisted of an otherwise similar TV watching session without electrically induced blinking. Subjective ocular symptoms were evaluated with a Dry Eye Questionnaire and visual acuity was assessed with a Logarithm of the Minimum Angle of Resolution (LogMAR) chart before and after both sessions. Results : The stimulation produced a blink in 8 participants (53%). The visual acuity in the affected eye decreased during the control session, whereas no significant change occurred during the stimulation session. The ocular symptoms were significantly reduced during the stimulation session. Conclusions : Electrically elicited blink is a promising method for reducing the eye symptoms in individuals with acute facial nerve palsy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Learning outcome is modified by the degree to which the subject responds and pays attention to specific stimuli. Our recent research suggests that presenting stimuli in contingency with a specific phase of the cardiorespiratory rhythm might expedite learning. Specifically, expiration-diastole (EXP-DIA) is beneficial for learning trace eyeblink conditioning (TEBC) compared with inspiration-systole (INS-SYS) in healthy young adults. The aim of this study was to investigate whether the same holds true in healthy elderly adults ( n = 50, aged >70 yr). Participants were instructed to watch a silent nature film while TEBC trials were presented at either INS-SYS or EXP-DIA (separate groups). Learned responses were determined as eyeblinks occurring after the tone conditioned stimulus (CS), immediately preceding the air puff unconditioned stimulus (US). Participants were classified as learners if they made at least five conditioned responses (CRs). Brain responses to the stimuli were measured by electroencephalogram (EEG). Memory for the film and awareness of the CS-US contingency were evaluated with a questionnaire. As a result, participants showed robust brain responses to the CS, acquired CRs, and reported awareness of the CS-US relationship to a variable degree. There was no difference between the INS-SYS and EXP-DIA groups in any of the above. However, when only participants who learned were considered, those trained at EXP-DIA ( n = 11) made more CRs than those trained at INS-SYS ( n = 13). Thus, learned performance could be facilitated in those elderly who learned. However, training at a specific phase of cardiorespiratory rhythm did not increase the proportion of participants who learned. NEW & NOTEWORTHY We trained healthy elderly individuals in trace eyeblink conditioning, either at inspiration-systole or at expiration-diastole. Those who learned exhibited more conditioned responses when trained at expiration-diastole rather than inspiration-systole. However, there was no difference between the experimental groups in the proportion of individuals who learned or did not learn.

Purpose: This study aimed to evaluate the functionality of the brainstem structures through the blink reflex (BR) test in patients with obstructive sleep apnoea (OSA) and to assess the effects of continuous positive airway pressure (CPAP) treatment on BR responses., Methods: Patients with moderate-severe OSA and controls underwent BR testing. Patients with OSA who were adherent to CPAP therapy repeated BR testing at 6 months follow-up. CPAP adherence was defined as CPAP use for ≥ 4 hour per night on > 5 nights per week with residual apnoea-hypopnea index less than 5 events per hour., Results: A total of 22 patients with OSA (86% male, mean age 57.8 ± 10.6 years) and 20 controls (60% male, mean age 55.3 ± 9.3 years) were included. Patients with OSA showed longer right and left R1 latency, as well as delayed right ipsilateral and contralateral R2 latencies compared to controls. Patients with OSA who were compliant with CPAP treatment (n = 16; 88% men, mean age 58.8 ± 9.7 years) showed a significant decrease in latency of the right ipsilateral and contralateral R2 responses at 6 months., Conclusion: This study showed an abnormal pattern of BR responses in patients with OSA, consistent with a significant impairment of brainstem functionality in OSA. CPAP treatment partially improved the BR responses, suggesting the importance of treating OSA., (© 2023. The Author(s).)

Face perception is a major topic in vision research. Most previous research has concentrated on (holistic) spatial representations of faces, often with static faces as stimuli. However, faces are highly dynamic stimuli containing important temporal information. How sensitive humans are regarding temporal information in dynamic faces is not well understood. Studies investigating temporal information in dynamic faces usually focus on the processing of emotional expressions. However, faces also contain relevant temporal information without any strong emotional expression. To investigate cues that modulate human sensitivity to temporal order, we utilized muted dynamic neutral face videos in two experiments. We varied the orientation of the faces (upright and inverted) and the presence/absence of eye blinks as partial dynamic cues. Participants viewed short, muted, monochromic videos of models vocalizing a widely known text (National Anthem). Videos were played either forward (in the correct temporal order) or backward. Participants were asked to determine the direction of the temporal order for each video, and (at the end of the experiment) whether they had understood the speech. We found that face orientation, and the presence/absence of an eye blink affected sensitivity, criterion (bias) and reaction time: Overall, sensitivity was higher for upright compared to inverted faces, and in the condition where an eye blink was present compared to the condition without an eye blink. Reaction times were mostly faster in the conditions with higher sensitivity. A bias to report inverted faces as 'backward' observed in Experiment I, where upright and inverted faces were presented randomly interleaved within each block, was absent when presenting upright and inverted faces in different blocks in Experiment II. Language comprehension results revealed that there was higher sensitivity when understanding the speech compared to not understanding the speech in both experiments. Taken together, our results showed higher sensitivity with upright compared to inverted faces, suggesting that the perception of dynamic, task-relevant information was superior with the canonical orientation of the faces. Furthermore, partial information coming from eye blinks, in addition to mouth movements, seemed to play a significant role in dynamic face perception, both when faces were presented upright and inverted. We suggest that studying the perception of facial dynamics beyond emotional expressions will help us to better understand the mechanisms underlying the temporal integration of facial information from different -partial and holistic- sources, and that our results show how different strategies, depending on the available information, are employed by human observers when judging the temporal order of faces., (© 2024. The Author(s).)

Trace eyeblink conditioning (TEBC) has been widely used to study associative learning in both animals and humans. In this paradigm, conditioned responses (CRs) to conditioned stimuli (CS) serve as a measure for retrieving learned associations between the CS and the unconditioned stimuli (US) within a trial. Memory consolidation, that is, learning over time, can be quantified as an increase in the proportion of CRs across training sessions. However, how hippocampal oscillations differentiate between successful memory retrieval within a session and consolidation across TEBC training sessions remains unknown. To address this question, we recorded local field potentials (LFPs) from the rat dorsal hippocampus during TEBC and investigated hippocampal oscillation dynamics associated with these two functions. We show that transient broadband responses to the CS were correlated with memory consolidation, as indexed by an increase in CRs across TEBC sessions. In contrast, induced alpha (8-10 Hz) and beta (16-20 Hz) band responses were correlated with the successful retrieval of the CS-US association within a session, as indexed by the difference in trials with and without CR., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Kim et al.)

According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones-more likely depression, upbound microzones-more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Geminiani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Blinks, the closing and opening of the eyelids, are used in a wide array of fields where human function and behavior are studied. In data from video-based eye trackers, blink rate and duration are often estimated from the pupil-size signal. However, blinks and their parameters can be estimated only indirectly from this signal, since it does not explicitly contain information about the eyelid position. We ask whether blinks detected from an eye openness signal that estimates the distance between the eyelids (EO blinks) are comparable to blinks detected with a traditional algorithm using the pupil-size signal (PS blinks) and how robust blink detection is when data quality is low. In terms of rate, there was an almost-perfect overlap between EO and PS blink (F1 score: 0.98) when the head was in the center of the eye tracker's tracking range where data quality was high and a high overlap (F1 score 0.94) when the head was at the edge of the tracking range where data quality was worse. When there was a difference in blink rate between EO and PS blinks, it was mainly due to data loss in the pupil-size signal. Blink durations were about 60 ms longer in EO blinks compared to PS blinks. Moreover, the dynamics of EO blinks was similar to results from previous literature. We conclude that the eye openness signal together with our proposed blink detection algorithm provides an advantageous method to detect and describe blinks in greater detail., (© 2024. The Author(s).)

Eye tracking is prevalent in scientific and commercial applications. Recent computer vision and deep learning methods enable eye tracking with off-the-shelf webcams and reduce dependence on expensive, restrictive hardware. However, such deep learning methods have not yet been applied and evaluated for remote, online psychological experiments. In this study, we tackle critical challenges faced in remote eye tracking setups and systematically evaluate appearance-based deep learning methods of gaze tracking and blink detection. From their own homes and laptops, 65 participants performed a battery of eye tracking tasks including (i) fixation, (ii) zone classification, (iii) free viewing, (iv) smooth pursuit, and (v) blink detection. Webcam recordings of the participants performing these tasks were processed offline through appearance-based models of gaze and blink detection. The task battery required different eye movements that characterized gaze and blink prediction accuracy over a comprehensive list of measures. We find the best gaze accuracy to be 2.4° and precision of 0.47°, which outperforms previous online eye tracking studies and reduces the gap between laboratory-based and online eye tracking performance. We release the experiment template, recorded data, and analysis code with the motivation to escalate affordable, accessible, and scalable eye tracking that has the potential to accelerate research in the fields of psychological science, cognitive neuroscience, user experience design, and human-computer interfaces., (© 2023. The Author(s).)

Purpose: While lacrimal gland removal is commonly used in animal models to replicate dry eye disease, research into systematically monitoring dry eye disease's longitudinal pathological changes is limited. In vivo confocal microscopy (Heidelberg Retina Tomograph 3 with a Rostock Cornea Module, Heidelberg Engineering Inc., Franklin, MA) can non-invasively reveal corneal histopathological structures. To monitor dry-eye-disease-related changes in corneal structures, we developed a precise monitoring method using in vivo confocal microscopy in a rat double lacrimal gland removal model., Methods: Five Sprague-Dawley rats (age 8-9 weeks, male) underwent double lacrimal gland removal. Modified Schirmer's tear test, blink tests, and in vivo confocal microscopy images were acquired pre-surgery and at 1, 2, and 4 weeks post-surgery. Three individual stromal nerves were selected per eye as guide images, and images of the corresponding sub-basal nerve plexus area were acquired via volume acquisition. The same area was re-imaged in subsequent weeks., Results: After double lacrimal gland removal, tear production was reduced by 60%, and the blink rate increased 10 times compared to pre-surgery. Starting from 1 week after surgery, in vivo confocal microscopy showed increased sub-basal nerve plexus nerve fiber density with inflammatory cell infiltration at the sub-basal nerve plexus layer and remained at an elevated level at 2 and 4 weeks post-surgery., Conclusions: We demonstrated that our precise monitoring method revealed detailed changes in the corneal nerves, the epithelium, and the stroma., (Copyright © 2024 Molecular Vision.)

Chronic pain (CP) significantly impacts quality of life and poses an increasing economic burden on healthcare systems worldwide. This study investigates the relationship between blink rate during saccadic eye movements and pain perception in patients with CP. Ninety-two patients with CP (24 men, 68 women) were assessed using eye-tracking technology during horizontal and vertical saccadic tasks. Pain perception was evaluated using the Central Sensitization Inventory - Part A and the McGill Pain Questionnaire, and anxiety levels were measured using the State-Trait Anxiety Inventory. The results revealed a significant correlation between blink rates in horizontal and vertical tasks (ρ = 0.668, P < 0.001). However, there was no correlation between blink rate and age, pain perception, or anxiety scores. Conversely, measures of pain perception were positively correlated with each other and with anxiety scores. These findings suggest that while blink rate may reflect oculomotor function, it is not directly influenced by pain perception or anxiety in patients with CP. The present study highlights the potential of eye tracking for the comprehensive assessment and management of patients with CP., Competing Interests: The authors declare no conflict of interest., (© 2024 by the authors.)

Background/aim: In this study, we investigated the blink reflex (BR) after simultaneous and asynchronous stimulation of two trigeminal nerve branches. The objective was to characterize the physiology of trigeminal and facial circuits., Materials and Methods: We performed three sets of experiments: recording BR response i. after supraorbital nerve stimulation (SON), after mental nerve stimulation (MN), and after simultaneous SON and MN stimulation (SON+MN) in 18 healthy individuals; ii. after MN (at an intensity eliciting BR response) preceding SON at various interstimulus intervals (ISIs) in seven healthy subjects; iii after MN (at sensory threshold) preceding SON at various ISIs. We compared the magnitudes of early and late responses., Results: The R1 amplitude after simultaneous SON+MN stimulation was greater than responses after single stimulation of the same branches. After simultaneous stimulations, the R2 and R2c areas under the curve (AUC) were smaller than the arithmetic sums of R2 and R2c AUC obtained after single stimulations. The second experiment provided a recovery excitability curve. In the third step, we obtained facilitation of R1 and inhibition of late responses., Conclusion: The SON+MN stimulation caused an increased R1 circuit excitability compared to the arithmetic sum of the single stimulations; however, magnitudes of late responses did not potentiate. Thus, we have provided evidence for R1 circuit enhancement by simultaneous stimulation in humans, whereas modulation of late responses exhibited a recovery curve similar to that shown for paired SON stimulation., Competing Interests: Conflict of interest: The authors report that they have no no conflicts of interest., (© TÜBİTAK.)

Background: Facial palsy causes paralytic lagophthalmos, which remarkably deteriorates a patient's quality of life. In cases where denervation time is over 18-24 months (longstanding facial palsy), a free or pedicled muscle transfer is needed to replace the denervated orbicularis oculi muscle., Purpose: The purpose of this systematic review is to investigate the effect of various eye sphincter substitution procedures (free or pedicled muscle transfers) in longstanding facial palsy patients on eye closure and blink., Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic review of the Embase, Medline, Web of Science and Cochrane Library databases and Google Scholar. Our literature search yielded 4322 articles. Following a full-text review, 4 retrospective cohort studies and 21 case series were selected for this review. Meta-analyses using R package meta (version 6.5-0) were conducted., Main Findings: All free and pedicled muscle transfers in this review showed an improvement in the scores and measurements on eye closure and blink. The pedicled temporalis muscle transfer was the procedure most commonly performed as eye reanimation surgery and showed consistent good results. Using the random effects model, the pooled effect of mean difference in lagophthalmos after gentle eye closure post-operatively versus pre-operatively (mm) in patients who received a pedicled (temporalis) muscle transfer was -6.19 (I 2 = 85%, 95% CI: -7.89; -4.49) whereas it was -4.11 (I 2 = 85%, 95% CI: -7.26; -0.95) for free (gracilis or platysma) muscle transfers. The pooled proportion of patients with complete eye closure after surgery was 0.69 (I 2 = 49%, 95% CI: 0.54; 0.82) in patients who received a pedicled (temporalis) muscle transfer and 0.40 (I 2 = 74%, 95% CI: 0.13; 0.74) in patients who received a free (platysma) muscle transfer., Conclusions: Unlike smile reanimation, dynamic eye closure and blink restoration are rather neglected topics in facial reanimation. The pedicled temporalis muscle transfer is often recommended as the first treatment of choice for eye reanimation in longstanding facial palsy patients since it is a reliable, straightforward procedure, that does not require complex microsurgery. However, with the advancements in the field of microsurgery, free muscle transfers are promising therapies, which may regenerate voluntary and spontaneous blinking., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable marker of facial bradykinesia. We tested 31 PD patients and 31 controls. Participants were filmed during conversation and a rapid blinking task. Both tasks were videorecorded to count the number of blinks per second. PD patients had lower blink rates. Rapid blinking accurately discriminated between groups with 77% sensitivity and 71% specificity. To conclude, rapid blinking may be a simple and quantifiable task of facial bradykinesia.

Objective: Spontaneous eyeblink rate (SEBR) is inversely proportional to the level of attentional focus in humans. The objective of this study was to evaluate the effects of attentional focus on SEBR in horses. Procedures: Twenty client‐owned horses (2.5‐23 years of age, five mares, 15 geldings) were evaluated. A GoPro HERO5 Session™ video recorder was attached to the halter and directed toward the eyes. Horses were acclimated for two hours before study commencement. Horses were filmed in five scenarios requiring different levels of attention: alone in a stall ("stall"), stall with an observer ("person"), standing in an arena ("stand"), walking in an arena ("walk"), and trotting in arena ("trot"). Each of the five scenarios was filmed for ten minutes. Video recordings were reviewed, and SEBR (incomplete, complete, and total blinks) was measured for both eyes in each scenario. Results: The median (25%,75%) total SEBRs (blinks/min) were as follows: STALL: OD‐16.6 (12.4, 24.3), OS‐18.8 (11.5, 26.9); PERSON: OD‐17.7 (14.6, 24.2), OS‐17.4 (13.9, 24.4); STAND: OD‐18.7 (15.1, 24.4), OS‐19.4 (16.2, 24.7); WALK: OD‐40.1 (34.1, 44.8), OS‐40.6 (33.8, 44.7); and TROT: OD‐39.7 (30.3, 44.6), OS‐39.4 (28.6, 45.0). The total SEBRs at walk and trot were significantly greater than SEBR in stationary scenarios. Conclusions: Despite requiring increased levels of attentional focus, activities involving motion caused increased SEBR in horses. We hypothesize the need for additional tear distribution due to tear evaporation (associated with air movement over the corneas) prevailed over the level of attentional focus to increase the SEBR. [ABSTRACT FROM AUTHOR]

Purpose: Herpes stromal keratitis (HSK) represents a spectrum of pathologies which is caused by herpes simplex virus type 1 (HSV-1) infection and is considered a leading cause of infectious blindness. HSV-1 infects corneal sensory nerves and establishes latency in the trigeminal ganglion (TG). Recently, retraction of sensory nerves and replacement with "unsensing" sympathetic nerves was identified as a critical contributor of HSK in a mouse model where corneal pathology is caused by primary infection. This resulted in the loss of blink reflex, corneal desiccation, and exacerbation of inflammation leading to corneal opacity. Despite this, it was unclear whether inflammation associated with viral reactivation was sufficient to initiate this cascade of events., Methods: We examined viral reactivation and corneal pathology in a mouse model with recurrent HSK by infecting the cornea with HSV-1 (McKrae) and transferring (intravenous [IV]) human sera to establish primary infection without discernible disease and then exposed the cornea to UV-B light to induce viral reactivation., Results: UV-B light induced viral reactivation from latency in 100% of mice as measured by HSV-1 antigen deposition in the cornea. Further, unlike conventional HSK models, viral reactivation resulted in focal retraction of sensory nerves and corneal opacity. Dependent on CD4+ T cells, inflammation foci were innervated by sympathetic nerves., Conclusions: Collectively, our data reveal that sectoral corneal sensory nerve retraction and replacement of sympathetic nerves were involved in the progressive pathology that is dependent on CD4+ T cells after viral reactivation from HSV-1 latency in the UV-B induced recurrent HSK mouse model.

When presented with a periodic stimulus, humans spontaneously adjust their movements from reacting to predicting the timing of its arrival, but little is known about how this sensorimotor adaptation changes across development. To investigate this, we analyzed saccade behavior in 114 healthy humans (ages 6-24 years) performing the visual metronome task, who were instructed to move their eyes in time with a visual target that alternated between two known locations at a fixed rate, and we compared their behavior to performance in a random task, where target onsets were randomized across five interstimulus intervals (ISIs) and thus the timing of appearance was unknown. Saccades initiated before registration of the visual target, thus in anticipation of its appearance, were labeled predictive [saccade reaction time (SRT) < 90 ms] and saccades that were made in reaction to its appearance were labeled reactive (SRT > 90 ms). Eye-tracking behavior including saccadic metrics (e.g., peak velocity, amplitude), pupil size following saccade to target, and blink behavior all varied as a function of predicting or reacting to periodic targets. Compared with reactive saccades, predictive saccades had a lower peak velocity, a hypometric amplitude, smaller pupil size, and a reduced probability of blink occurrence before target appearance. The percentage of predictive and reactive saccades changed inversely from ages 8-16, at which they reached adult-levels of behavior. Differences in predictive saccades for fast and slow target rates are interpreted by differential maturation of cerebellar-thalamic-striatal pathways. SIGNIFICANCE STATEMENT From the first moments of life, humans are exposed to rhythm (i.e., mother's heartbeat in utero ), but the timeline of brain development to promote the identification and anticipation of a rhythmic stimulus, known as temporal prediction, remains unknown. Here, we used saccade reaction time (SRT) in the visual metronome task to differentiate between temporally predictive and reactive responses to a target that alternated at a fixed rate in humans aged 6-24. Periods of age-related change varied little by target rate, with matured predictive performance evident by mid-adolescence for fast and slow rates. A strong correlation among saccade, pupil, and blink responses during target prediction provides evidence of oculomotor coordination and dampened noradrenergic neuronal activity when generating rhythmic motor responses., (Copyright © 2022 the authors.)

Pupillometry, thanks to its strong relationship with cognitive factors and recent advancements in measuring techniques, has become popular among cognitive or neural scientists as a tool for studying the physiological processes involved in mental or neural processes. Despite this growing popularity of pupillometry, the methodological understanding of pupillometry is limited, especially regarding potential factors that may threaten pupillary measurements' validity. Eye blinking can be a factor because it frequently occurs in a manner dependent on many cognitive components and induces a pulse-like pupillary change consisting of constriction and dilation with substantive magnitude and length. We set out to characterize the basic properties of this "blink-locked pupillary response (BPR)," including the shape and magnitude of BPR and their variability across subjects and blinks, as the first step of studying the confounding nature of eye blinking. Then, we demonstrated how the dependency of eye blinking on cognitive factors could confound, via BPR, the pupillary responses that are supposed to reflect the cognitive states of interest. By building a statistical model of how the confounding effects of eye blinking occur, we proposed a probabilistic-inference algorithm of de-confounding raw pupillary measurements and showed that the proposed algorithm selectively removed BPR and enhanced the statistical power of pupillometry experiments. Our findings call for attention to the presence and confounding nature of BPR in pupillometry. The algorithm we developed here can be used as an effective remedy for the confounding effects of BPR on pupillometry., Competing Interests: The authors have declared that no competing interests exist.

We studied nine normal volunteers with a classical conditioning paradigm using a mastoid tap, believed to activate otolith receptors, as an unconditional stimulus (US) and the consequent blink as the unconditioned response (UR). Both visual (alternation of stripes) and an auditory tone were used as conditional stimuli (CS). Recordings were made below the eyes at IO1 and IO2, from over the frontal eye fields (C3' and C4') and over the posterior fossa, the latter at sites we have previously reported that we were able to record an evoked climbing fibre response (CFR) at short latency. Behavioural analysis confirmed that weak conditioning did occur early, which subsequently showed extinction on repeated CS alone trials. Further, a UR was more likely to occur following a preceding CFR when preceded by a CS, supporting a correlation between the CFRs and behaviour. For further statistical analysis, the time period of interest was divided into a series of epochs, based around the events occurring at the time. Grand averages, plus analysis of variance, confirmed evidence of weak conditioning for the blink response following both modalities. The EMG associated with the eyeblink for the UR occurred at a similar time to the expected post-CFR pause in the spontaneous cerebellar activity, or electrocerebellogram (ECeG), while hypothesised conditioned pausing in the ECeG was also observed in CS alone trials. A correlation was found between the size of the CFR and the RMS amplitudes of the segments covering the ocular vestibular evoked myogenic potential oVEMP, (periocular) EMG and the EOG. The slope was greater for the non-oVEMP segments than for the oVEMP segment suggesting the correlation was not simply due to differing sizes of the vestibular volley. We suggest that these recorded events fit with the proposed role of the CFR in Purkinje neurons in classical conditioning, gating the excitability of the cerebellar nuclei, and thereby neurons in the reticular formation mediating the otolith blink reflex. This effect appears to apply to polysynaptic reflexes only as there was no evidence of changes to the oVEMP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Magnetoencephalography (MEG) is a functional neuroimaging tool that records the magnetic fields induced by neuronal activity; however, signal from non-neuronal sources can corrupt the data. Eye-blinks, saccades, and cardiac activity are three of the most common sources of non-neuronal artifacts. They can be measured by affixing eye proximal electrodes, as in electrooculography (EOG), and chest electrodes, as in electrocardiography (ECG), however this complicates imaging setup, decreases patient comfort, and can induce further artifacts from movement. This work proposes an EOG- and ECG-free approach to identify eye-blinks, saccades, and cardiac activity signals for automated artifact suppression. The contribution of this work is three-fold. First, using a data driven, multivariate decomposition approach based on Independent Component Analysis (ICA), a highly accurate artifact classifier is constructed as an amalgam of deep 1-D and 2-D Convolutional Neural Networks (CNNs) to automate the identification and removal of ubiquitous whole brain artifacts including eye-blink, saccade, and cardiac artifacts. The specific architecture of this network is optimized through an unbiased, computer-based hyperparameter random search. Second, visualization methods are applied to the learned abstraction to reveal what features the model uses and to bolster user confidence in the model's training and potential for generalization. Finally, the model is trained and tested on both resting-state and task MEG data from 217 subjects, and achieves a new state-of-the-art in artifact detection accuracy of 98.95% including 96.74% sensitivity and 99.34% specificity on the held out test-set. This work automates MEG processing for both clinical and research use, adapts to the acquired acquisition time, and can obviate the need for EOG or ECG electrodes for artifact detection., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)