Evaluating a Novel, Portable, Self-Administrable Device ("Beacon") That Measures Critical Flicker Frequency as a Test for Hepatic Encephalopathy.

INTRODUCTION: We compared critical flicker frequency (CFF) thresholds obtained using a novel portable device "Beacon" with thresholds from the commercially available Lafayette Flicker Fusion System (Lafayette-FFS) in patients with cirrhosis. METHODS: One hundred fifty-three participants with chronic liver disease underwent CFF testing using Beacon and Lafayette-FFS with a method-of-limits and/or forced-choice protocol. RESULTS: Beacon demonstrated excellent test-retest reliability (intraclass correlation 0.91-0.97) and good correlation with the Lafayette-FFS values (intraclass correlation 0.77-0.84). Forced-choice CFF were on average 4.1 Hz higher than method-of-limits descending CFFs. DISCUSSION: Beacon can be self-administered by patients with chronic liver disease and cirrhosis to measure CFF, a validated screening test for minimal hepatic encephalopathy.

Is critical flicker-fusion frequency a valid measure of visual fatigue? A post-hoc analysis of a double-masked randomised controlled trial.

PURPOSE: Critical flicker-fusion frequency (CFF) has been used in clinical studies as a measure of visual fatigue. We examine the correlation between CFF and subjective reports of visual fatigue in a group of symptomatic computer users, to consider whether CFF may be used as a surrogate measure of visual fatigue symptoms. METHODS: We analysed data from a previous randomised controlled trial. One hundred and twenty adults, diagnosed with computer vision syndrome, had CFF and visual fatigue symptoms quantified before and after a visually demanding 2-h computer task. Symptoms were assessed using a questionnaire with nine subcomponents that summed to a total score of 900. CFF was measured using a two-interval forced-choice method, with the flicker rate altered by a computer-controlled staircase procedure. For our primary analysis, we determined Spearman correlation coefficients between post-task symptom scores and CFF, and between change from baseline symptom scores and CFF. We also used a bootstrap procedure to consider whether symptom score subcomponents were significantly (Bonferroni-corrected) different from overall scores with regard to their correlations with CFF. RESULTS: Although visual fatigue symptom scores altered significantly post-task (mean change: 92 units; 95% confidence interval [CI]: 11 to 122), CFF did not (mean change -0.7 Hz; 95% CI: -1.7 to 0.3). There was no significant correlation between overall symptom scores and CFF, either for the post-task (r = -0.13; 95% CI: -0.31 to 0.05) or the change from baseline (r = -0.18; 95% CI: -0.35 to 0.01) analysis. Subcomponents of the symptom questionnaire did not show a significant correlation with CFF, either for the post-task or the change from baseline analysis. CONCLUSIONS: We find that CFF is not a useful surrogate for symptoms of visual fatigue, given its low correlation with scores on a visual fatigue symptom questionnaire.

Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.

Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.

Reply to Mankowska et al. Comment on "Muth et al. Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review. Medicina 2023, 59, 800".

First and foremost, we like to express our gratitude for the praise bestowed upon our narrative review [...].

Comment on Muth et al. Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review. Medicina 2023, 59, 800.

We first want to thank the authors of the excellent review for their contributions to summarizing the confounders associated with critical flicker fusion frequency (CFFF) [...].

Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review.

The critical flicker fusion frequency (cFFF) refers to the frequency at which a regularly recurring change of light stimuli is perceived as steady. The cFFF threshold is often assessed in clinics to evaluate the temporal characteristics of the visual system, making it a common test for eye diseases. Additionally, it serves as a helpful diagnostic tool for various neurological and internal diseases. In the field of diving/hyperbaric medicine, cFFF has been utilized to determine alertness and cognitive functions. Changes in the cFFF threshold have been linked to the influence of increased respiratory gas partial pressures, although there exist inconsistent results regarding this effect. Moreover, the use of flicker devices has produced mixed outcomes in previous studies. This narrative review aims to explore confounding factors that may affect the accuracy of cFFF threshold measurements, particularly in open-field studies. We identify five broad categories of such factors, including (1) participant characteristics, (2) optical factors, (3) smoking/drug use, (4) environmental aspects, and (5) breathing gases and partial pressures. We also discuss the application of cFFF measurements in the field of diving and hyperbaric medicine. In addition, we provide recommendations for interpreting changes in the cFFF threshold and how they are reported in research studies.

The visual cortex produces gamma band echo in response to broadband visual flicker.

The aim of this study is to uncover the network dynamics of the human visual cortex by driving it with a broadband random visual flicker. We here applied a broadband flicker (1-720 Hz) while measuring the MEG and then estimated the temporal response function (TRF) between the visual input and the MEG response. This TRF revealed an early response in the 40-60 Hz gamma range as well as in the 8-12 Hz alpha band. While the gamma band response is novel, the latter has been termed the alpha band perceptual echo. The gamma echo preceded the alpha perceptual echo. The dominant frequency of the gamma echo was subject-specific thereby reflecting the individual dynamical properties of the early visual cortex. To understand the neuronal mechanisms generating the gamma echo, we implemented a pyramidal-interneuron gamma (PING) model that produces gamma oscillations in the presence of constant input currents. Applying a broadband input current mimicking the visual stimulation allowed us to estimate TRF between the input current and the population response (akin to the local field potentials). The TRF revealed a gamma echo that was similar to the one we observed in the MEG data. Our results suggest that the visual gamma echo can be explained by the dynamics of the PING model even in the absence of sustained gamma oscillations.

Usefulness of critical flicker fusion frequency measurement and its laterality for evaluating compressive optic neuropathy due to pituitary neuroendocrine tumors.

Critical flicker fusion frequency (CFF) is a short but sensitive method for evaluating optic nerve function. We measured CFF in patients with pituitary neuroendocrine tumors (Pit-NETs) to assess its usefulness. Data from 184 patients with nonfunctioning Pit-NETs, who had been treated with transsphenoidal surgery and had no medical history of eye diseases, was used in this retrospective study. Visual acuity decline (VAD) was defined as > 0.10 reduction in logMAR visual acuity and CFF decline (CFD) was defined as CFF value < 35 Hz. Visual field defect (VFD) was evaluated by automated perimetry on a Humphrey visual field analyzer. Potential associations between abnormal test results and tumor height from the suprasellar were analyzed. Contact between the optic nerve or chiasma and the tumor was present and absent in 161 and 23 patients, respectively. In patients showing contact, the difference in CFF between the left and right eyes was larger (p = 0.0008), and the optimal cutoff value using the receiver operating characteristic curve was 3 Hz. Therefore, ≥ 3 Hz was considered positive for CFF laterality (CFL), the most prevalent condition. Tumor height was lower in patients with CFL positivity compared to those with VAD or VFD (p < 0.01). The prevalence of test abnormalities was the highest for small tumors compared to those of other tests. Changes in CFL permit early detection of Pit-NETs. Our results indicate that CFF laterality can be seen in the early stages of compressive optic neuropathy due to Pit-NET.

Comment on Mankowska et al. Critical Flicker Fusion Frequency: A Narrative Review. Medicina 2021, 57, 1096.

We have read with great interest the review by Mankowska et al. [...].

Reply to Vrijdag et al. Comment on "Mankowska et al. Critical Flicker Fusion Frequency: A Narrative Review. Medicina 2021, 57, 1096".

Thank you very much for your interest and comments [...].

Maintenance of normal fusion in intermittent exotropia.

PURPOSE: To evaluate the reliability of the Bagolini filter bar and striated lenses for measuring the fusion maintenance score, which is the ability of participants with intermittent exotropia to maintain normal sensorimotor fusion. METHODS: Thirty-two Chinese participants aged 7-20 years with intermittent exotropia (excluding the convergence insufficiency type) were enrolled in this prospective study. At the eligibility screening, visual acuity, cover test and assessment of the office control score were performed. At study visit 1, eligible participants underwent negative and positive fusional vergence tests at far and near, eye dominance test and the fusion maintenance test. All eligible participants returned for study visit 2 on the same day (2-4 h later) and the testing was repeated. The primary outcome measure was the intra-class correlation coefficient of the fusion maintenance score between the two study visits. RESULTS: The intra-class correlation coefficient of the fusion maintenance score was 0.84, indicating good reliability. There was no significant difference (mean difference = 0.05, p = 0.95) between the fusion maintenance scores for the first (5.62) and second study visits (5.57). The coefficient of repeatability and the smallest detectable change for the fusion maintenance scores were 7.6 and 6.3, respectively. The fusion maintenance score was significantly associated with the distance (Spearman correlation -0.57, p < 0.001) and near (Spearman correlation -0.4, p = 0.02) office control scores. CONCLUSION: These data demonstrate that the fusion maintenance score is a reliable tool to evaluate sensorimotor fusion in intermittent exotropia. These results suggest that the fusion maintenance score may be a useful outcome measure in future clinical trials to evaluate the effectiveness of treatments for intermittent exotropia.

Evaluation of cerebral dysfunction in patients with chronic kidney disease using neuropsychometric and neurophysiological tests.

BACKGROUND: Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). OBJECTIVE: To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. METHODS: This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < -4 for PHES. All participants were also screened for cognitive function and depression. RESULTS: Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. CONCLUSIONS: It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.

Critical Flicker Fusion Frequency: A Narrative Review.

This review presents the current knowledge of the usage of critical flicker fusion frequency (CFF) in human and animal model studies. CFF has a wide application in different fields, especially as an indicator of cortical arousal and visual processing. In medicine, CFF may be helpful for diagnostic purposes, for example in epilepsy or minimal hepatic encephalopathy. Given the environmental studies and a limited number of other methods, it is applicable in diving and hyperbaric medicine. Current research also shows the relationship between CFF and other electrophysiological methods, such as electroencephalography. The human eye can detect flicker at 50-90 Hz but reports are showing the possibility to distinguish between steady and modulated light up to 500 Hz. Future research with the use of CFF is needed to better understand its utility and application.

Evolutionary constraints on flicker fusion frequency in Lepidoptera.

Flying insects occupy both diurnal and nocturnal niches, and their visual systems encounter distinct challenges in both conditions. Visual adaptations, such as superposition eyes of moths, enhance sensitivity to low light levels but trade off with spatial and temporal resolution. Conversely, apposition eyes of butterflies enable high spatial resolution but are poorly sensitive in dim light. Although diel activity patterns of insects influence visual processing, their role in evolution of visual systems is relatively unexplored. Lepidopteran insects present an excellent system to study how diel activity patterns and phylogenetic position influence the visual transduction system. We addressed this question by comparing electroretinography measurements of temporal response profiles of diverse Lepidoptera to light stimuli that were flickering at different frequencies. Our data show that the eyes of diurnal butterflies are sensitive to visual stimuli of higher temporal frequencies than nocturnal moths. Hesperiid skippers, which are typically diurnal or crepuscular, exhibit intermediate phenotypes with peak sensitivity across broader frequency range. Across all groups, species within families exhibited similar phenotypes irrespective of diel activity. Thus, Lepidopteran photoreceptors may have diversified under phylogenetic constraints, and shifts in their sensitivity to higher temporal frequencies occurred concomitantly with the evolution of diurnal lifestyles.

Effect of change saliency and neural entrainment on flicker-induced time dilation.

When a visual stimulus flickers periodically and rhythmically, the perceived duration tends to exceed its physical duration in the peri-second range. Although flicker-induced time dilation is a robust time illusion, its underlying neural mechanisms remain inconclusive. The neural entrainment account proposes that neural entrainment of the exogenous visual stimulus, marked by steady-state visual evoked potentials (SSVEPs) over the visual cortex, is the cause of time dilation. By contrast, the saliency account argues that the conscious perception of flicker changes is indispensable. In the current study, we examined these two accounts separately. The first two experiments manipulated the level of saliency around the critical fusion threshold (CFF) in a duration discrimination task to probe the effect of change saliency. The amount of dilation correlated with the level of change saliency. The next two experiments investigated whether neural entrainment alone could also induce perceived dilation. To preclude change saliency, we utilized a combination of two high-frequency flickers above the CFF, whereas their beat frequency still theoretically aroused neural entrainment at a low frequency. Results revealed a moderate time dilation induced by combinative high-frequency flickers. Although behavioral results suggested neural entrainment engagement, electroencephalography showed neither larger power nor inter-trial coherence (ITC) at the beat. In summary, change saliency was the most critical factor determining the perception and strength of time dilation, whereas neural entrainment had a moderate influence. These results highlight the influence of higher-level visual processing on time perception.

How does cognitive function measured by the reaction time and critical flicker fusion frequency correlate with the academic performance of students?

BACKGROUND: The reaction time (RT) is "the time taken for the appearance of rapid voluntary reaction by an individual following a stimulus, either auditory or visual" and the Critical Flickering Fusion Frequency (CFFF) is "the rate at which successively presented light stimuli appear to be steady and continuous". RT and CFFF are commonly used for the assessment of cognitive functions that are known to influence academic performance. However, data about the exact correlation between these are scarce, particularly in India. This research aimed to study the association between visual RT (VRT), auditory RT (ART) and CFFF and their impact on the academic performance of undergraduate students. METHODS: This cross-sectional study was conducted on 700 students of Faculty of Medicine and Dentistry at a private medical university in South India, during the period from 2015 to 2017. The VRT, ART and CFFF were evaluated, and the best out of three subsequent attempts was recorded. The mean score (in percentage) of the three best marks out of the five internal assessments for the course during each academic year was considered for analysis. The association between the different cognitive tests and the average academic performance was analysed. RESULTS: Female students had faster VRT (n = 345, mean = 243.97, SD = 83.87) than male students (n = 273, mean = 274.86, SD = 96.97) (p = 0.001). VRT and ART had a moderate negative correlation with academic performance (for ART, r = - 0.42, p < 0.001; for VRT; r = - 0.40, p < 0.001). CFFF had a very weak positive correlation with academic performance (r = 0.19, p = 0.01). The only independent predictors of academic performance were RT and gender (Adjusted R2 = 0.11). CONCLUSION: Although there is a correlation between CFFF and cognitive function, our study showed only a weak correlation between CFFF and academic performance. Female students had faster RTs, and gender was an independent predictor of academic performance. Rather, students with faster RTs appear to have an advantage in academic performance.

Olfaction Warps Visual Time Perception.

Our perception of the world builds upon dynamic inputs from multiple senses with different temporal resolutions, and is threaded with the passing of subjective time. How time is extracted from multisensory inputs is scantly known. Utilizing psychophysical testing and electroencephalography, we show in healthy human adults that odors modulate object visibility around critical flicker-fusion frequency (CFF)-the limit at which chromatic flickers become perceived as a stable color-and effectively alter CFF in a congruency-based manner, despite that they afford no clear environmental temporal information. The behavioral gain produced by a congruent relative to an incongruent odor is accompanied by elevated neural oscillatory power around the object's flicker frequency in the right temporal region ~150-300 ms after object onset, and is not mediated by visual awareness. In parallel, odors bias the subjective duration of visual objects without affecting one's temporal sensitivity. These findings point to a neuronal network in the right temporal cortex that executes flexible temporal filtering of upstream visual inputs based on olfactory information. Moreover, they collectively indicate that the very process of sensory integration at the stage of object processing twists time perception, hence casting new insights into the neural timing of multisensory events.

Inert gas narcosis in scuba diving, different gases different reactions.

PURPOSE: Underwater divers face several potential neurological hazards when breathing compressed gas mixtures including nitrogen narcosis which can impact diver's safety. Various human studies have clearly demonstrated brain impairment due to nitrogen narcosis in divers at 4 ATA using critical flicker fusion frequency (CFFF) as a cortical performance indicator. However, recently some authors have proposed a probable adaptive phenomenon during repetitive exposure to high nitrogen pressure in rats, where they found a reversal effect on dopamine release. METHODS: Sixty experienced divers breathing Air, Trimix or Heliox, were studied during an open water dive to a depth of 6 ATA with a square profile testing CFFF measurement before (T0), during the dive upon arriving at the bottom (6 ATA) (T1), 20 min of bottom time (T2), and at 5 m (1.5 ATA) (T3). RESULTS: CFFF results showed a slight increase in alertness and arousal during the deep dive regardless of the gas mixture breathed. The percent change in CFFF values at T1 and T2 differed among the three groups being lower in the air group than in the other groups. All CFFF values returned to basal values 5 min before the final ascent at 5 m (T3), but the Trimix measurements were still slightly better than those at T0. CONCLUSIONS: Our results highlight that nitrogen and oxygen alone and in combination can produce neuronal excitability or depression in a dose-related response.

A 23-Year-Old Woman with Sudden-Onset Blindness of the Right Eye.

A 23-year-woman was presented for sudden-onset monocular blindness. Branch retinal artery occlusion in the right eye and multiple brain embolism were detected. Trousseau syndrome due to bilateral ovarian cancer was diagnosed; no embolic events were observed after anticoagulant therapy and surgical resection.

Evaluation of Central Fatigue by the Critical Flicker Fusion Threshold in Cyclists.

Central fatigue related in sport stimuli was studied by Critical Flicker Fusion Threshold (CFFT) to know the influence of exercise on the central nervous system (CNS), but there is a lack of knowledge about the central or peripheral fatigue in endurance events. This study aimed to analyze changes in CFFT before and after the incremental cycle ergometer test as a means to assess the fatigue of the CNS. CFFT ascending and descending, the subjective criterion and sensory sensitivity were analysed in 8 professional male cyclists (72.1 ± 5.59 kg, 180.3 ± 6.43 cm, 17.4 ± 0.7 years) before and after a maximum incremental cycle ergometer test (start 50w increases 50w each 5 min). In this incremental test, the induced fatigue was probably more a peripheral phenomenon than one due to central nervous system fatigue, because sensory sensitivity did not significantly decrease. In conclusion, an incremental cycle ergometer test increased the cortical arousal and does not affect negatively the CNS of professional cyclists.