Search Results (41)

The menstrual cycle affects the autonomic nervous system (ANS), cognition, and emotional valence in all biological women. There exists a complex relationship between hormonal fluctuations, ANS, cognition, and emotional valence during the different phases of the menstrual cycle, which includes menstruation, the follicular phase, ovulation, and the luteal phase. Hence, this narrative review is an attempt to comprehensively understand the effects of the menstrual cycle on the structural and functional integrity of the ANS. In order to provide a comprehensive understanding of the complex relationship between the menstrual cycle, hormonal fluctuations, and ANS function in biological women, this review examines key parameters, including heart rate variability (HRV), baroreflex sensitivity (BRS), muscle sympathetic nerve activity (MSNA), and pupillary light reflex (PLR), to investigate how these physiological systems are dynamically influenced by the cyclical changes in hormone levels and how these fluctuations impact various physiological and psychological outcomes, such as mood, cognition, and emotional regulation. There have been several studies previously performed to assess these parameters during different phases of the menstrual cycle. However, the results have been contradictory; therefore, this review explores possible reasons behind these inconsistent results, with likely reasons including irregularity in the menstrual cycles and differences in hormonal fluctuations between different women during similar phases of the menstrual cycle. Overall, there appears to be evidence to suggest that the menstrual cycle has both direct and indirect effects on ANS, cognition, and emotional valence, whilst measures of ANS may provide a means for assessing the effect of the menstrual cycle. Full article

Background and Objectives: Vision uses about half of the pathways within the brain, and these anatomical structures are susceptible to injury in concussion. Authors have suggested that subconcussive head impacts, common in soccer, may disrupt visual function. The following study aimed to explore and compare quantitative pupillometry and Vestibular Ocular Motor Screening (VOMS) in female soccer athletes. Materials and Methods: Twenty-six Division 1 female soccer athletes (20.46 ± 2.36 years) received baseline quantitative pupillometry and VOMS measurements. Results: Of the 26 tested athletes, 3 (11.5%) had clinically significant pupillometry findings at baseline. The mean Neurological Pupil Index or NPi, a composite generated from pupillometry, did not vary: 3.9 ± 0.4 (right eye) and 4.0 ± 0.4 (left eye). No difference in NPi was observed compared to the VOMS score (p > 0.05). Kruskal–Wallis H tests were significant in the right eye for constriction percentage (χ²(2) = 17.843, p < 0.001, E² = 0.69) and minimum pupil size (χ²(2) = 7.976, p = 0.019, E² = 0.31). A post hoc Dunn test showed significant differences in constriction percentage and minimum pupil size between low NPi and high NPi groups (p < 0.05). One athlete sustained a concussion. NPi was measured within 24 h and was normal, but VOMS was not (total score = 4). Conclusions: The components of pupillometry need more investigation, and there is a need for agreement on concussion-specific cutoffs for quantitative pupillometry for concussion assessment. The lack of a relationship between quantitative pupillometry and VOMS suggests that these tools evaluate different constructs. Athletes with an NPi < 3.8 had significantly less constriction percentage and larger minimum pupil size than athletes with higher NPi scores. More research should be carried out to determine the usefulness of the NPi score, and perhaps researchers should consider individual pupillometry components. Full article

Background/Objectives: Impaired consciousness has various causes. One such cause includes hypoglycemia, which may be symptomatic or asymptomatic and is associated with high mortality. Autonomic abnormalities are also common in hypoglycemic patients. Early detection is critical for improving prognosis. In this study, we evaluated changes in vital signs and pupillary responses before and after glucose administration in patients with hypoglycemia managed in a prehospital emergency setting. Methods: This retrospective observational study included 583 adult patients from the Tokyo Fire Department database. All patients were suspected by emergency medical technicians (EMTs) to have hypoglycemia-related impaired consciousness and showed improved consciousness after receiving intravenous glucose infusion at the scene. Vital signs, level of consciousness, and pupillary responses were assessed before and after glucose administration. Results: The mean patient age was 58.9 years, and approximately 90% had comorbid diabetes mellitus. Tachypnea was common at the scene, with 27% showing tachycardia, while blood pressure remained normal. Miosis and abnormal pupillary light reflexes were observed in 68% and 84% of cases, respectively. Anisocoria occurred in 7.6% of the patients. After glucose administration, both abnormal reflexes and anisocoria significantly decreased (both p < 0.0001). Although vital signs did not consistently reflect autonomic responses, changes in pupillary findings were prominent. Conclusions: Altered pupillary responses are common in hypoglycemic coma. Findings such as miosis and anisocoria can result from various causes, including central nervous system disorders and cholinergic toxicity; thus, careful differential diagnosis is essential. Normal blood pressure may help to distinguish hypoglycemic coma during prehospital care. Full article

Background/Objectives: The pathological changes preceding the onset of Parkinson’s disease (PD) commence several decades before motor symptoms manifest, offering a potential window for identifying objective biomarkers for early diagnosis and disease monitoring. Among the primary non-motor features of PD is autonomic dysfunction; however, its precise assessment remains challenging, limiting its viability as a reliable biomarker. Both the pupillary light reflex (PLR) and pupillary unrest are regulated by autonomic pathways suggesting their potential as objective non-invasive indicators of the PD prodromal phase. This review systematically evaluates studies that compare PLR and pupillary unrest in individuals with PD and healthy controls to determine their utility as potential biomarkers of the disease. Methods: A systematic search strategy was designed to identify studies reporting PLR and pupillary unrest findings in PD patients. Searches were conducted across three databases (MEDLINE, Embase PsycINFO), supplemented by cross-referencing relevant studies found on Google Scholar. The literature search was last updated on 7 December 2020. Pupillometric parameters that permitted statistical synthesis included maximum constriction velocity (VMax), constriction amplitude (CAmp), and constriction latency (CL). Pooled incidence and effect sizes were determined using a random-effects model with an inverse variance DerSimonian–Laird estimator. The I² statistic was used to assess study heterogeneity. When meta-analysis was not feasible, a qualitative analysis was undertaken. Results: The initial search yielded 219 references. Following deduplication and exclusion of ineligible studies, 31 papers were selected for review. Pupillometric data from 11 studies were incorporated into the meta-analysis. Effect sizes for PD patients were significant for VMax −0.92, (p < 0.01), CAmp −0.58, (p < 0.05), and CL 0.46, (p < 0.05). Measures of pupillary unrest were elevated in PD patients compared to controls, but evidence was limited to two studies. Conclusions: Pupillary constriction in response to light is characterised by reduced speed and amplitude in PD, with effect sizes suggesting potential clinical applicability. However, evidence regarding baseline pupillary variability remains insufficient, underlining the necessity for further research. Pupillary metrics represent a promising avenue for early PD detection, though their clinical utility is constrained by methodological heterogeneity and variations in disease duration among studies. Full article

Brain–computer interface (BCI)-based assistive technologies enable intuitive and efficient user interaction, significantly enhancing the independence and quality of life of elderly and disabled individuals. Although existing wet EEG-based systems report high accuracy, they suffer from limited practicality. This study presents a hybrid BCI system combining dry-type EEG-based flash visual-evoked potentials (FVEP) and pupillary light reflex (PLR) designed to control an LED-based meal-assist robot. The hybrid system integrates dry-type EEG and eyewear-type infrared cameras, addressing the preparation challenges of wet electrodes, while maintaining practical usability and high classification performance. Offline experiments demonstrated an average accuracy of 88.59% and an information transfer rate (ITR) of 18.23 bit/min across the four target classifications. Real-time implementation uses PLR triggers to initiate the meal cycle and EMG triggers to detect chewing, indicating the completion of the cycle. These features allow intuitive and efficient operation of the meal-assist robot. This study advances the BCI-based assistive technologies by introducing a hybrid system optimized for real-world applications. The successful integration of the FVEP and PLR in a meal-assisted robot demonstrates the potential for robust and user-friendly solutions that empower the users with autonomy and dignity in their daily activities. Full article

Melanopsin contribution to visual and non-visual effect has drawn widespread concern. However, research about whether this contribution can be applied to display system design is limited. Here, a four-primary display system was designed and constructed based on three projectors with filters to realize isolation control of melanopsin and cones, and a 65-inch uniform display area was achieved. The melanopic luminance metamers (higher and lower) of different colours have been modulated thusly. The effect of melanopic luminance on pupillary light reflex (PLR) and brightness perception was explored under a luminous environment of 300 lx to ensure the saturation of rod. The results showed that the higher melanopic luminance level contributed to delayed contraction maintenance. Moreover, a log relationship was found between melanopic equivalent daylight luminance and pupillary contraction maintenance parameters with coefficient of determination more than 0.85. Furthermore, stimuli of higher melanopic luminance level appeared brighter, indicating that melanopsin contributed to brightness perception. Full article

Background/Objectives: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. Methods: A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Results: Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Conclusions: Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies. Full article

Background: Handheld quantitative pupilometers (QPs) measure each phase of the pupillary light reflex (PLR) and provide a summary score based on these values. One phase of the PLR is the period of time from the onset of light exposure to the maximum constriction of the pupil, also known as time to maximum constriction (tMC). Although tMC has been found to vary significantly among patients with neurological injury, there are no studies reporting tMC in healthy controls. This study addresses this gap. Methods: Subjects in this prospective observational study were healthy controls who provided paired (left and right eye) QP readings during four separate observations over the course of 2 days. The tMC was derived by determining the smallest observed pupil size during videos filmed at 30 frames per second, and we assessed within-subject variability using the coefficient of variance and intraclass correlation coefficient (ICC). Results: Fifty subjects provided 380 QP readings (190 left eye and 190 right eye). Subjects primarily identified as female (80%), non-Hispanic (86%), white (62%), and <40 years old (74%). The mean tMC was 1.0 (0.14) seconds (s) for the left eye and 1.0 (0.17) s for the right eye; the coefficient of variance ranged from 11.6% to 18.8% and the ICC ranged from 0.25 to 0.40. For the between-subject comparisons across the four observation periods, the left and right eye mean differences ranged from 0.001 to 0.063 and the ICC ranged from 0.12 to 0.52. Conclusions: The tMC values vary significantly in healthy controls. Changes in pupil function as a clinical biomarker of intracranial pathology are not fully understood. Identifying clinical correlations of tMC variation may provide insight for the prognostication and treatment of neurocritically ill patients. Full article

Background: Quantitative pupillometry has been proposed as an objective means to diagnose acute sports-related concussion (SRC). Objective: To assess the diagnostic accuracy of a smartphone-based quantitative pupillometer in the acute diagnosis of SRC. Methods: Division I college football players had baseline pupillometry including pupillary light reflex (PLR) parameters of maximum resting diameter, minimum diameter after light stimulus, percent change in pupil diameter, latency of pupil constriction onset, mean constriction velocity, maximum constriction velocity, and mean dilation velocity using a smartphone-based app. When an SRC occurred, athletes had the smartphone pupillometry repeated as part of their concussion testing. All combinations of the seven PLR parameters were tested in machine learning binary classification models to determine the optimal combination for differentiating between non-concussed and concussed athletes. Results: 93 football athletes underwent baseline pupillometry testing. Among these athletes, 11 suffered future SRC and had pupillometry recordings repeated at the time of diagnosis. In the machine learning pupillometry analysis that used the synthetic minority oversampling technique to account for the significant class imbalance in our dataset, the best-performing model was a random forest algorithm with the combination of latency, maximum diameter, minimum diameter, mean constriction velocity, and maximum constriction velocity PLR parameters as feature inputs. This model produced 91% overall accuracy, 98% sensitivity, 84.2% specificity, area under the curve (AUC) of 0.91, and an F1 score of 91.6% in differentiating between baseline and SRC recordings. In the machine learning analysis prior to oversampling of our imbalanced dataset, the best-performing model was k-nearest neighbors using latency, maximum diameter, maximum constriction velocity, and mean dilation velocity to produce 82% accuracy, 40% sensitivity, 87% specificity, AUC of 0.64, and F1 score of 24%. Conclusions: Smartphone pupillometry in combination with machine learning may provide fast and objective SRC diagnosis in football athletes. Full article

The early components of the pupillary light reflex (PLR) are governed by the parasympathetic nervous system. The use of cheap, portable pupillometry devices may allow for the testing of parasympathetic-system health in field settings. We examined the reliability of two portable instruments for measuring the PLR and their sensitivity to individual differences known to modulate the PLR. Parameters of the PLR were measured in a community sample (N = 108) in a variety of field settings. Measurements were taken using a commercial pupillometer (NeuroLight, IDMED) and an iPhone using the Reflex Pro PLR analyser (Brightlamp). The parameters of baseline pupil diameter, constriction latency, amplitude and relative amplitude of constriction, and constriction velocity were measured. Individual differences related to age, levels of anxiety, and post-traumatic stress disorder (PTSD) symptomology were assessed. Some measures could not be attained using the iPhone under these field conditions. The reliability of the measures was high, save for the measurement of contraction latency which was particularly unreliable for the iPhone system. The parameters of the PLR showed the same internal relationships as those established in laboratory-based measurements. Age was negatively correlated with all the reliable PLR parameters for both systems. Effects of anxiety and PTSD symptomology were also apparent. The study demonstrated that a hand-held portable infrared pupillometer can be used successfully to measure the PLR parameters under field settings and can be used to examine individual differences. This may allow these devices to be used in workplaces, sports fields, roadsides, etc., to examine parasympathetic activity where needed. Full article

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that modulates the noradrenergic activity of the locus coeruleus (LC). Yet, there is still uncertainty about the most effective stimulation and reliable outcome parameters. In a double blind, sham-controlled study including a sample of healthy young individuals (N = 29), we compared a shorter (3.4 s) and a longer (30 s) stimulation duration and investigated the effects of taVNS (real vs. sham) on saliva samples (alpha amylase and cortisol concentration), pupil (pupillary light reflex and pupil size at rest) and EEG data (alpha and theta activity at rest, ERPs for No-Go signals), and cognitive tasks (Go/No-Go and Stop Signal Tasks). Salivary alpha amylase concentration was significantly increased in the real as compared to sham stimulation for the 30 s stimulation condition. In the 3.4 s stimulation condition, we found prolonged reaction times and increased error rates in the Go/No-Go task and increased maximum acceleration in the pupillary light reflex. For the other outcomes, no significant differences were found. Our results show that prolonged stimulation increases salivary alpha-amylase, which was expected from the functional properties of the LC. The finding of longer response times to short taVNS stimulation was not expected and cannot be explained by an increase in LC activity. We also discuss the difficulties in assessing pupil size as an expression of taVNS-mediated LC functional changes. Full article

Background: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. Methods: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics^®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable’s β coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. Results: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. Conclusions: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS. Full article

This article employed pupillometry as a non-invasive technique to analyze pupillary light reflex (PLR) using LED flash stimuli. Particularly, for the experiments, only the red LED with a wavelength of 600 nm served as the light stimulation source. To stabilize the initial pupil size, a pre-stimulus (PRE) period of 3 s was implemented, followed by a 1 s stimulation period (ON) and a 4 s post-stimulus period (POST). Moreover, an experimental, low-cost pupillometer prototype was designed to capture pupillary images of 13 participants. The prototype consists of a 2-megapixel web camera and a lighting system comprising infrared and RGB LEDs for image capture in low-light conditions and stimulus induction, respectively. The study reveals several characteristic features for classifying the phenomenon, notably the mobility of Hjórth parameters, achieving classification percentages ranging from 97% to 99%, and offering novel insights into pattern recognition in pupillary activity. Moreover, the proposed device successfully captured the PLR from all the participants with zero reported incidents or health affectations. Full article

Background: Concussion examination is based primarily on clinical evaluation and symptomatic reporting. Pupillary light reflex (PLR) metrics may provide an objective physiological marker to inform concussion diagnosis and recovery, but few studies have assessed PLR, and normative data are lacking, particularly for adolescents. Aim: To capture PLR data in adolescent rugby players and examine the effects of concussion history and biological sex. Design: Cross-sectional. Methods: Male and female adolescent rugby union players aged 16 to 18 years were recruited at the start of the 2022–2023 playing season. PLR was recorded using a handheld pupillometer which provided seven different metrics relating to pupil diameter, constriction/dilation latency, and velocity. Data were analysed using a series of 2 × 2 ANOVAs to examine the main effects of independent variables: biological sex, concussion history, and their interactions, using adjusted p-values (p < 0.05). Results: 149 participants (75% male) were included. A total of 42% reported at least one previous concussion. Most metrics were unaffected by the independent variables. There were however significant main effects for concussion history (F = 4.11 (1); p = 0.05) and sex (F = 5.42 (1); p = 0.02) in end pupil diameters, and a main effect for sex in initial pupil diameters (F = 4.45 (1); p = 0.04). Although no significant interaction effects were found, on average, females with a concussion history presented with greater pupillary diameters and velocity metrics, with many pairwise comparisons showing large effects (SMD > 0.8). Conclusions: Pupillary diameters in adolescent athletes were significantly affected by concussion history and sex. The most extreme PLR metrics were recorded in females with a history of concussion (higher pupillary diameters and velocities). This highlights the importance of establishing baseline PLR metrics prior to interpretation of the PLR post-concussion. Long-standing PLR abnormalities post-concussion may reflect ongoing autonomic nervous system dysfunction. This warrants further investigation in longitudinal studies. Full article

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer’s disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O₂) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD. Full article