Variant Impact Predictor database (VIPdb), version 2: trends from three decades of genetic variant impact predictors.

BACKGROUND: Variant interpretation is essential for identifying patients' disease-causing genetic variants amongst the millions detected in their genomes. Hundreds of Variant Impact Predictors (VIPs), also known as Variant Effect Predictors (VEPs), have been developed for this purpose, with a variety of methodologies and goals. To facilitate the exploration of available VIP options, we have created the Variant Impact Predictor database (VIPdb). RESULTS: The Variant Impact Predictor database (VIPdb) version 2 presents a collection of VIPs developed over the past three decades, summarizing their characteristics, ClinGen calibrated scores, CAGI assessment results, publication details, access information, and citation patterns. We previously summarized 217 VIPs and their features in VIPdb in 2019. Building upon this foundation, we identified and categorized an additional 190 VIPs, resulting in a total of 407 VIPs in VIPdb version 2. The majority of the VIPs have the capacity to predict the impacts of single nucleotide variants and nonsynonymous variants. More VIPs tailored to predict the impacts of insertions and deletions have been developed since the 2010s. In contrast, relatively few VIPs are dedicated to the prediction of splicing, structural, synonymous, and regulatory variants. The increasing rate of citations to VIPs reflects the ongoing growth in their use, and the evolving trends in citations reveal development in the field and individual methods. CONCLUSIONS: VIPdb version 2 summarizes 407 VIPs and their features, potentially facilitating VIP exploration for various variant interpretation applications. VIPdb is available at  https://genomeinterpretation.org/vipdb.

Updated benchmarking of variant effect predictors using deep mutational scanning.

The assessment of variant effect predictor (VEP) performance is fraught with biases introduced by benchmarking against clinical observations. In this study, building on our previous work, we use independently generated measurements of protein function from deep mutational scanning (DMS) experiments for 26 human proteins to benchmark 55 different VEPs, while introducing minimal data circularity. Many top-performing VEPs are unsupervised methods including EVE, DeepSequence and ESM-1v, a protein language model that ranked first overall. However, the strong performance of recent supervised VEPs, in particular VARITY, shows that developers are taking data circularity and bias issues seriously. We also assess the performance of DMS and unsupervised VEPs for discriminating between known pathogenic and putatively benign missense variants. Our findings are mixed, demonstrating that some DMS datasets perform exceptionally at variant classification, while others are poor. Notably, we observe a striking correlation between VEP agreement with DMS data and performance in identifying clinically relevant variants, strongly supporting the validity of our rankings and the utility of DMS for independent benchmarking.

Crossed VEP asymmetry in a patient with AHR-linked infantile nystagmus and foveal hypoplasia.

INTRODUCTION: Infantile nystagmus and foveal hypoplasia associated with AHR gene defects is a newly recognized and rare disorder. Our aim was to present a patient with a novel biallelic AHR pathogenic variant with electrophysiological evidence of chiasmal misrouting. MATERIALS AND METHODS: Complete ocular examination, fundus imaging, visual evoked potentials (VEP) and full-field electroretinography were performed at initial presentation. Genetic testing was performed by whole exome sequencing. RESULTS: Female patient of 6 years old presented a reduced best corrected visual acuity, an infantile nystagmus and a grade III typical foveal hypoplasia without ocular hypopigmentation. A crossed asymmetry was discovered on pattern onset/offset VEP. Genetic testing put in evidence a novel homozygous variant in AHR: c.2242del, p. (Gln748Lysfs*5). During 11-years follow-up period, BCVA gradually improved. There was no evidence of retinal degeneration. CONCLUSION: AHR gene defects could be associated with infantile nystagmus, foveal hypoplasia and chiasmal misrouting.

Objective detection of visual field defects with multifrequency VEPs.

PURPOSE: To correlate multifrequency pattern reversal VEPs in quadrants (QmfrVEPs) with perimetric field losses for objective detection of visual field losses. METHODS: QmfrVEP measurements were performed using four LED-based checkerboard stimulators to stimulate the four quadrants of the visual field. QmfrVEPs were measured monocularly in 5 normal subjects and in 5 glaucoma patients who showed losses in conventional Octopus perimetry. The pattern reversal frequency varied slightly between the stimulators: (11.92, 12.00, 12.08 and 12.16 reversals/sec). The responses to the different stimuli were identified by discrete Fourier analysis. VEPs were recorded using different electrode configurations, and the recording with the highest signal-to-noise ratio (SNR) was used for further analysis. RESULTS: QmfrVEP responses from the different quadrants can be reliably measured and separated using the 0.08 reversals/sec interstimulus reversal frequency differences. The signal-to-noise ratio in the four quadrants was significantly correlated with the equivalent visual field losses obtained with perimetry (Spearman rank correlation: P < 0.001). In the five glaucoma patients, the SNR was reduced in 15 out of the 16 quadrants with a perimetric defect, in comparison to the results in quadrants of healthy subjects. This confirms the sensitivity of the procedure. CONCLUSION: QmfrVEP responses can be measured reliably. This pilot study suggests that high SNR values exclude visual field defects and that focal defects can be identified in glaucoma patients. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . NCT00494923.

Genetic Linkage between CAPN5 and TYR Variants in the Context of Albinism and Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy Absence: A Case Report.

We present a case involving a patient whose clinical phenotype aligns with oculocutaneous albinism (OCA), yet exhibits a complex genotype primarily characterized by variants of unknown significance (VUS). An 11-year-old boy manifested iris hypopigmentation and translucency, pronounced photophobia, diminished visual acuity and stereopsis, nystagmus, reduced pigmentation of the retina, and foveal hypoplasia. Genetic testing was performed. A heterozygous missense VUS CAPN5 c.230A>G, p.(Gln77Arg), a heterozygous missense VUS TYR c.1307G>C, p.(Gly436Ala), and a heterozygous missense variant TYR c.1205G>A, p.(Arg402Gln) which was classified as a risk factor, were identified. We hypothesized that the TYR c.1307G>C, p.(Gly436Ala) variant is in genetic disequilibrium with the TYR c.1205G>A, p.(Arg402Gln) variant leading to deficient expression of melanogenic enzymes in retinal cells, resulting in the manifestation of mild OCA. Additionally, this study represents the case where we did not detect chiasmal misrouting in visual evoked potentials, nor did we observe a shift in the distribution of ganglion cell thickness from a temporal to a central position. Moreover, our patient's case supports the probable benign nature of the CAPN5 c.230A>G, p.(Gln77Arg) variant.

Pattern visual evoked potentials show an inferior-superior topographic shift through maturation in childhood.

The pattern-reversal visual evoked potential (prVEP) is an established routine clinical test. Its objectivity is particularly valuable for assessing visual pathway function in children. International standards specify at a minimum that an active electrode is placed on the occiput at Oz, but we find an additional inferior electrode at the inion (Iz) provides larger and more sensitive prVEPs in young persons. This study assesses the significance and age-dependence of these observations. PrVEPs were recorded from 1487 patients considered ophthalmologically normal aged <20 years old, to a range of check widths including International Society for Clinical Electrophysiology of Vision (ISCEV) standard large (50') and small (12.5') check widths. P100 peak-time and amplitude from both electrode sites were analysed. A subset of 256 children were studied longitudinally by fitting logistic regression models including a random effect on subjects. PrVEPs were largest over the Iz electrode for the majority of infants and children. This transitioned with age to become equal or smaller at Oz as a function of check width. For ISCEV standard large and small check widths, transition periods were ∼8 and ∼12 years of age, respectively. We estimated abnormal result classifications of 3.7% with use of an Oz electrode alone, which decreases to 0.0-0.5% when adding or using an Iz electrode. The inferior dominance of prVEP topography in children may be explained by age-related anatomical changes altering the cortical dipole, combined with physiological maturation of the neural generators of the prVEP. We recommend the Iz electrode is used routinely in recording of prVEPs in children. KEY POINTS: Pattern visual evoked potentials (PVEPs) are an established clinical test which provide objective assessment of visual pathway function. These are particularly valuable in providing objective information of vision in children. International standards specify the active recording electrode should be placed at the mid-occiput (Oz), but we find that pattern-reversal visual evoked potential amplitudes are larger for a lower placed electrode (Iz) in young persons. This was assessed in 1487 patients who had simultaneous PVEP recording at both electrode positions, and it was found that the majority of PVEPs in children were larger over the Iz electrode. The developmental differences in PVEP distribution transitioned to be equal between Iz and Oz with increasing age as a function of check width, at ∼8 and ∼12 years old for large and small check widths, respectively. These differences will improve diagnostic accuracy of paediatric PVEPs. We hypothesise these changes reflect developmental anatomical and neurophysiological changes altering the PVEP dipole.

Burst c-VEP Based BCI: Optimizing stimulus design for enhanced classification with minimal calibration data and improved user experience.

The utilization of aperiodic flickering visual stimuli under the form of code-modulated Visual Evoked Potentials (c-VEP) represents a pivotal advancement in the field of reactive Brain-Computer Interface (rBCI). A major advantage of the c-VEP approach is that the training of the model is independent of the number and complexity of targets, which helps reduce calibration time. Nevertheless, the existing designs of c-VEP stimuli can be further improved in terms of visual user experience but also to achieve a higher signal-to-noise ratio, while shortening the selection time and calibration process. In this study, we introduce an innovative variant of code-VEP, referred to as "Burst c-VEP". This original approach involves the presentation of short bursts of aperiodic visual flashes at a deliberately slow rate, typically ranging from two to four flashes per second. The rationale behind this design is to leverage the sensitivity of the primary visual cortex to transient changes in low-level stimuli features to reliably elicit distinctive series of visual evoked potentials. In comparison to other types of faster-paced code sequences, burst c-VEP exhibit favorable properties to achieve high bitwise decoding performance using convolutional neural networks (CNN), which yields potential to attain faster selection time with the need for less calibration data. Furthermore, our investigation focuses on reducing the perceptual saliency of c-VEP through the attenuation of visual stimuli contrast and intensity to significantly improve users' visual comfort. The proposed solutions were tested through an offline 4-classes c-VEP protocol involving 12 participants. Following a factorial design, participants were instructed to focus on c-VEP targets whose pattern (burst and maximum-length sequences) and amplitude (100% or 40% amplitude depth modulations) were manipulated across experimental conditions. Firstly, the full amplitude burst c-VEP sequences exhibited higher accuracy, ranging from 90.5% (with 17.6s of calibration data) to 95.6% (with 52.8s of calibration data), compared to its m-sequence counterpart (71.4% to 85.0%). The mean selection time for both types of codes (1.5 s) compared favorably to reports from previous studies. Secondly, our findings revealed that lowering the intensity of the stimuli only slightly decreased the accuracy of the burst code sequences to 94.2% while leading to substantial improvements in terms of user experience. Taken together, these results demonstrate the high potential of the proposed burst codes to advance reactive BCI both in terms of performance and usability. The collected dataset, along with the proposed CNN architecture implementation, are shared through open-access repositories.

Neurophysiological visual assessment in patients with idiopathic intracranial hypertension: visual evoked potential and multifocal field electroretinography.

BACKGROUND: Determining the cause of visual deterioration in idiopathic intracranial hypertension (IIH) patients is of clinical necessity. This study aimed to study the effect of chronic increased ICP on the retina and optic nerve through objective electrophysiological measures in chronic IIH patients. METHODS: Thirty patients with chronic IIH and thirty age and sex-matched healthy controls were included in this study. Papilledema grade and CSF pressure were evaluated in the patients' group. Both groups were submitted to visual evoked potentials (VEP) and multifocal electroretinogram (mfERG). RESULT: The mean value of P100 latencies of the right and left on two check sizes, 1 deg and 15m in chronic IIH patients, was significantly delayed than controls (P-value < 0.001 for each). Chronic IIH patients showed a significantly lower amplitude of the right and left R1, R2, R3, R4 & R5 compared to controls (P-value < 0.001, < 0.001) (P-value < 0.001, < 0.001) (P-value < 0.001, < 0.001) (P-value < 0.001, = 0.001) (P-value = 0.002, < 0.001), respectively. Also, patients showed a significantly delayed peak time of the right and left R1 and R2 compared to controls (P-value < 0.001, < 0.001) (P-value = 0.001, = 0.009), respectively. There was a significant positive correlation between each of CSF pressure and papilledema grade with right and left PVEP latencies. In contrast, there was no statistically significant correlation between either CSF pressure or papilledema grade and PVEP amplitudes in both eyes. CONCLUSION: In chronic IIH patients, both optic nerve dysfunction and central retinal changes were identified, supported by VEP and the mfERG findings.

VEP examination with new portable device.

INTRODUCTION: We developed a new portable device called "VEPpeak" for the examination of visual evoked potentials (VEPs) to extend VEP examination beyond specialized electrophysiological laboratories and to simplify the use of this objective, noninvasive, and low-cost method for diagnostics of visual and central nervous system dysfunctions. METHODS: VEPpeak consists of a plastic headset with a total weight of 390 g containing four EEG amplifiers, an A/D converter, a control unit, and a visual LED stimulator built in the front, vertically adjustable peak. The device is powered and controlled via USB connection from a standard PC/notebook using custom software for visual stimuli generation and for VEP recording and processing. Up to four electrodes can be placed at any scalp location or in combination with two dry electrodes incorporated into the headset. External visual stimulators, such as a tablet, can be used with synchronization. Feasibility and validation studies were conducted with 86 healthy subjects and 76 neuro-ophthalmological patients including 67 who were during the same session also tested with a conventional VEP system. RESULTS: VEPpeak recordings to standard (pattern-reversal) and non-standard (motion-onset, red-green alternation) were robust and repeatable and obtained also in immobilized patients. Good comparability of results was achieved between VEPpeak and standard examination. Some systematic differences in peak latencies and amplitudes are consistent with differences in stimulus characteristics of the two compared systems. DISCUSSION: VEPpeak provides an inexpensive system for clinical use requiring portability. In addition to ISCEV standard VEP protocols, free choice of stimuli and bio-signal recordings make the device universal for many electrophysiological purposes.

Temporal frequency dependence of the polarity inversion between upper and lower visual field in the pattern-onset steady-state visual evoked potential.

PURPOSE: According to the cruciform model, the upper and lower halves of the visual field representation in the primary visual cortex are located mainly on the opposite sides of the calcarine sulcus. Such a shape would have consequences for the surface-recorded visual evoked potential (VEP), as V1 responses to stimulation of the upper and lower hemifield manifest with opposite polarity (i.e., polarity inversion). However, the steady-state VEP results from a complex superposition of response components from different cortical sources, which can obscure the inversion of polarity. The present study assesses the issue for different stimulation frequencies which result in different patterns of superposition in the steady-state response. METHODS: Sequences of brief pattern-onset stimuli were presented at different stimulation rates ranging from 2 Hz (transient VEP) to 13 Hz (steady-state VEP). The upper and lower hemifields were tested separately and simultaneously. The data were assessed both in the time domain and in the frequency domain. RESULTS: Comparing the responses to the stimulation of upper and lower hemifield, polarity inversion was present within a limited time interval following individual stimulus onsets. With increasing frequency, this resulted in an approximate inversion of the full steady-state response and consequently in a phase shift of approximately 180° in the time-domain response. Polarity inversion was more prominent at electrode Pz, also for transient responses. Our data also demonstrated that the sum of the hemifield responses is a good approximation of the full-field response. CONCLUSION: While the basic phenomenon of polarity inversion occurs irrespective of the stimulus frequency, its relative impact on the steady-state response as a whole is the largest for high stimulation rates. We propose that this is because longer-lasting response components from other visual areas are not well represented in the steady-state VEP at higher frequencies.

Pattern visual evoked potential and foveal sensitivity in amblyopia.

PURPOSE: Amblyopic eyes show impaired visual functions such as poor visual acuity and reduced foveal sensitivity. The purpose of this study was to determine the association between foveal threshold and visual evoked potentials (VEP) in strabismic and anisometropic amblyopia. METHODS: Forty-five subjects (age range: 7-28 years, 43.3% female) including 15 strabismic and 15 anisometropic amblyopes, and 15 age-similar control subjects participated in this study. Each subject had pattern visual evoked potentials and foveal threshold recorded in each eye using RetiScan (Roland Consult, Germany) and Humphrey Visual Field Analyzer II (HFA II; Carl Zeiss Meditec Inc., Dublin, CA), respectively. These outcomes were compared among the amblyopic eyes, their fellow eyes, and the control eyes. RESULTS: Compared to the amblyopic eyes (Mean ± SD: 33.4 ± 3.48 dB), the foveal threshold was higher in fellow eyes (37.0 ± 2.04 dB, p = 0.0002) and in control eyes (38.7 ± 0.96 dB, p < 0.0001). Strabismic amblyopes had a lower foveal threshold than anisometropic amblyopes (31.8 ± 3.86 vs. 35.0 ± 2.17 dB, p = 0.005). Relative to the P100 peak time in fellow eyes (1° checks:116.1 ± 9.00 ms; 0.25° checks:118.8 ± 5.67 ms), amblyopic eyes had delayed P100 peak times for both 1° (122.7 ± 11.4 ms, p < 0.0001) and 0.25° (130.4 ± 11.2 ms, p < 0.0001) check sizes. There were also significant differences in P100 peak time between amblyopic and control eyes (1°:122.7 ± 11.4 vs.112.4 ± 5.01 ms, p = 0.15; 0.25°:130.4 ± 11.2 vs.113.9 ± 5.71 ms, p < 0.0001) and between fellow and control eyes (0.25°:118.8 ± 5.67 vs.113.9 ± 5.71 ms, p = 0.009). Amblyopic eyes exhibited lower N75-P100 amplitudes than fellow eyes (1°:12.6 ± 7.96 vs.15.9 ± 8.82 µV, p = 0.01; 0.25°:10.6 ± 6.11 vs. 15.8 ± 10.6 µV, p = 0.001) and control eyes (0.25°: p = 0.0008). Foveal threshold correlated negatively with P100 peak time (1°: r = -0.45, p = 0.002 and 0.25°: r = -0.58, p < 0.0001) and positively with N75-P100 amplitude responses (1°: r = 0.42, p = 0.004 and 0.25°: r = 0.52, p = 0.002). CONCLUSIONS: Amblyopic eyes showed reduced pattern VEP amplitudes and delayed peak times with significant associations with the foveal sensitivity. However, the VEP measures overlapped extensively between amblyopic and control eyes with no apparent criterion value for optimal discrimination, suggesting that foveal sensitivity might be a better discriminator of amblyopia than pattern VEP.

Frequency-domain analysis of transient visual evoked potentials in schizophrenia.

PURPOSE: Frequency-domain measures were applied to characterize neural deficits in individuals with schizophrenia using transient visual evoked potentials (tVEP). These measures were compared with conventional time-domain measures to elucidate underlying neurophysiological mechanisms and examine the value of frequency analysis. METHODS: Four frequency bands of activity identified in previous work were explored with respect to magnitude (spectral power), timing (phase), a combined measure, magnitude-squared coherence (MSC), and compared to amplitudes and times of prominent deflections in the response. RESULTS: Band 2 power/MSC (14-28 Hz) captured the major deflections in the waveform and its power predicted N75-P100 amplitude for patients and controls. Band 3 power/MSC (30-40 Hz) correlated highly with the earliest deflection (P60-N75), reflecting input to primary visual cortex (V1) and produced the largest magnitude effect. Phase of the 24th harmonic component predicted P100 peak time for patients and controls and yielded the largest group difference. Cluster analyses including time- and frequency-domain measures identified subgroups of patients with differential neurophysiological effects. A small but significant difference in visual acuity was found between groups that appears to be neurally based: Acuity (range 0.63-1.6) was not correlated with any tVEP measures in controls nor with input timing to V1 (P60 peak time) in patients, but was correlated with later tVEP measures in patients. All but two of the patients were on antipsychotic medication: Medication level (chlorpromazine equivalents) was correlated negatively with tVEP time measures and positively with certain magnitude measures yielding responses similar to controls at high levels. CONCLUSIONS: Overall, frequency-domain measures were shown to be objective and recommended as an alternative to conventional, subjective time-domain measures for analyzing tVEPs and in distinguishing between groups (patients vs. controls and patient subgroups). The findings implicated a loss of excitatory input to V1 in schizophrenia. Acuity as measured in the current study reflected disease status, and medication level was associated with improved tVEP responses. These novel tVEP techniques may be useful in revealing neurophysiological processes affected in schizophrenia and as a clinical tool.

ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update).

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023.

Impact of keratoprosthesis implantation on retinal and visual pathway function assessed by electrophysiological testing.

PURPOSE: To investigate the impact of Boston Type I Keratoprosthesis (BI-Kpro) implantation on retinal and visual pathway function, respectively, assessed by full-field electroretinography (ERG) and visually evoked potentials (VEPs). METHODS: This is a prospective interventional longitudinal study, and patients with BI-Kpro implantation were assessed preoperatively and at 3 and 12 months after surgery. ERG, flash, and pattern-reversal VEPs (15' and 60' checks) along with visual acuity (VA) were performed. RESULTS: A total of 13 patients (24 to 88 years of age) were included. Mean baseline VA (logMAR) improved from 2.30 to 1.04 at 3 months and to 1.00 at 12 months. Flash VEPs were normal in 6 (46%) patients and in 10 (77%) patients at the 12-month follow-up. PVEP was non-detectable in all patients preoperatively for both check sizes. For 15' check size, 6 (46%) patients showed responses after 3 and 12 months except for 1 patient with normal responses at 12 months with the remaining non-detectable. For 60' checks, 11 (85%) patients had responses 3 months after surgery with only 9 (70%) showing responses at 12 months. Abnormal full-field ERGs were found in all patients preoperatively. Amplitude improvement was found in 10 (77%) patients from baseline to 3 months and in 8 (62%) patients from the 3- to the 12-month follow-up. CONCLUSIONS: In this small cohort of patients with BI-Kpro implantation, a remarkable improvement on visual function quantitatively assessed by electrophysiological testing was found in the majority of cases. Visual electrophysiological testing can contribute to objectively assess functional outcomes in this population.

Exaggerated response to pattern reversal visual evoked potential among migraineurs.

OBJECTIVE: Visual evoked potential recording has reported ambiguous results among migraineurs, thus the present study explored the association of check-size and reversal rates on the latency and amplitude of pattern reversal VEP among migraineurs. METHOD AND MATERIAL: Monocular VEP responses for both eyes were recorded in 133 migraineurs and 111 controls. Checkerboard pattern with phase reversal frequency of 0.5, 1, 2 and 4 Hz and check-size of 16 × 16, 32 × 32, 64 × 64 and 128 × 128, i.e. spatial frequency of 0.475, 1.029, 2.056 and 4.112 cycle per degree (cpd) were used to record 100 responses each. Three-minutes gap was given after change of reversal frequency to a higher rate for next cycle of 4 check-size records. RESULT: A linear increase in latencies was observed with decreasing check-size in both groups, but migraineurs had significantly higher latencies at a given reversal rate. Amplitudes A1 and A2 were higher among migraineurs and amplitude A2 showed an inverted 'U' shaped trend with maximum amplitude at 32 × 32 check size (1.029 cpd) in both groups, with an exaggerated response among migraineurs. Check-size 32 × 32 i.e. spatial frequency of 1.029 behaves differently than other larger or smaller check-sizes. CONCLUSION: Variable VEP response for different visual stimuli may be due to differential activation of respective retinocortical pathways and cortical areas. The highest amplitude at modest check-size suggests a contributory role of foveal-parafoveal fibres in migraineurs. Exaggerated physiological response to visual stimuli may be responsible for higher amplitudes and prolonged latencies among migraineurs.

Exaggerated physiological VEP response as higher amplitudes and prolonged latencies, among migraineurs may be due to differential activation of respective retinocortical pathways and cortical areas.

VEPdgets: Towards Richer Interaction Elements Based on Visually Evoked Potentials.

For brain-computer interfaces, a variety of technologies and applications already exist. However, current approaches use visual evoked potentials (VEP) only as action triggers or in combination with other input technologies. This paper shows that the losing visually evoked potentials after looking away from a stimulus is a reliable temporal parameter. The associated latency can be used to control time-varying variables using the VEP. In this context, we introduced VEP interaction elements (VEP widgets) for a value input of numbers, which can be applied in various ways and is purely based on VEP technology. We carried out a user study in a desktop as well as in a virtual reality setting. The results for both settings showed that the temporal control approach using latency correction could be applied to the input of values using the proposed VEP widgets. Even though value input is not very accurate under untrained conditions, users could input numerical values. Our concept of applying latency correction to VEP widgets is not limited to the input of numbers.

Evaluation of VEP parameters in patients before and after cardiopulmonary by-pass surgery.

PURPOSE: Coronary bypass surgery is emphasized in aetiology of ischemic optic neuropathy. Our aim in this study was to investigate the pattern visual evoked potentials (PVEP) in patients before and after coronary bypass surgery. METHODS: Thirty-one patients were included in the study. After a full ophthalmological evaluation, PVEP was assesed in the pre and postoperative periods. Operative times, hematological parameters, blood pressures, number of transfusions, body temperatures, anaesthetic drugs and systemic illnesses were recorded for each patient. RESULTS: The mean age of the patients were 59 ± 10.4 years. There was 22 men and 9 women in the study. Only 3 of them needed transfusion during the surgery. The mean duration of the surgery was 3.2 ± 0.7 h. None of the patients had a history of visual disturbance or postoperative ischemic optic neuropathy. The mean VEP P100 amplitude was not statistically significantly different but the mean VEP P100 latency showed statistically significant difference between the preoperative and postoperative periods. (p = 0.014) This significance was more appereant in patients with systemic illnesses. (p = 0.023) There was a positive correlation between the age and VEP P100 latency (r = 0.402, p < 0.05). CONCLUSIONS: Although surgical techniques and equipments are developing each day in the field of cardiopulmonary bypass surgery, the contributing factors such as hypothermia, anemia and diabetes still seem to affect neurophysiological functions even after a noncomplicated surgery.

Annotating and prioritizing genomic variants using the Ensembl Variant Effect Predictor-A tutorial.

The Ensembl Variant Effect Predictor (VEP) is a freely available, open-source tool for the annotation and filtering of genomic variants. It predicts variant molecular consequences using the Ensembl/GENCODE or RefSeq gene sets. It also reports phenotype associations from databases such as ClinVar, allele frequencies from studies including gnomAD, and predictions of deleteriousness from tools such as Sorting Intolerant From Tolerant and Combined Annotation Dependent Depletion. Ensembl VEP includes filtering options to customize variant prioritization. It is well supported and updated roughly quarterly to incorporate the latest gene, variant, and phenotype association information. Ensembl VEP analysis can be performed using a highly configurable, extensible command-line tool, a Representational State Transfer application programming interface, and a user-friendly web interface. These access methods are designed to suit different levels of bioinformatics experience and meet different needs in terms of data size, visualization, and flexibility. In this tutorial, we will describe performing variant annotation using the Ensembl VEP web tool, which enables sophisticated analysis through a simple interface.

The strength of feedback processing is associated with resistance to visual backward masking during Illusory Contour processing in adult humans.

Re-entrant feedback processing is a key mechanism of visual object-recognition, especially under compromised viewing conditions where only sparse information is available and object features must be interpolated. Illusory Contour stimuli are commonly used in conjunction with Visual Evoked Potentials (VEP) to study these filling-in processes, with characteristic modulation of the VEP in the ∼100-150 ms timeframe associated with this re-entrant processing. Substantial inter-individual variability in timing and amplitude of feedback-related VEP modulation is observed, raising the question whether this variability might underlie inter-individual differences in the ability to form strong perceptual gestalts. Backward masking paradig ms have been used to study inter-individual variance in the ability to form robust object perceptions before processing of the mask interferes with object-recognition. Some individuals recognize objects when the time between target object and mask is extremely short, whereas others struggle to do so even at longer target-to-mask intervals. We asked whether timing and amplitude of feedback-related VEP modulations were associated with individual differences in resistance to backward masking. Participants (N=40) showed substantial performance variability in detecting Illusory Contours at intermediate target-to-mask intervals (67 ms and 117 ms), allowing us to use kmeans clustering to divide the population into four performance groups (poor, low-average, high-average, superior). There was a clear relationship between the amplitude (but not the timing) of feedback-related VEP modulation and Illusory Contour detection during backward masking. We conclude that individual differences in the strength of feedback processing in neurotypical humans lead to differences in the ability to quickly establish perceptual awareness of incomplete visual objects.

Long term potentiation-like neural plasticity and performance-based memory function.

OBJECTIVE: Experience-dependent modulation of the visual evoked potential (VEP) has emerged as a promising non-invasive proxy for assaying long term potentiation (LTP)-like plasticity in the cerebral cortex. LTP is considered the principal candidate mechanism underlying learning and memory. There is, however, a paucity of evidence exploring associations between LTP-like plasticity and performance-based learning and memory. The present study aimed to explore the relationship between VEP-plasticity and higher-order learning and memory in healthy adults. METHOD: Visual and verbal learning and memory was assessed using the Aggie Figures Learning Test (AFLT) and the Rey Auditory Verbal Learning Test (RAVLT). The study included 111 healthy adults (61.1% females; mean age 37.6 years, range 17-71) who underwent a VEP paradigm employing visual high-frequency stimulation to induce a change in visual evoked responses recorded by scalp EEG. In addition, a more comprehensive neuropsychological assessment was administered. RESULTS: Several significant moderate age-corrected positive correlations were found between modulation of the later VEP components (N1 and P1-N1 peak-to-peak) and both visual and verbal learning and memory performance. Further, there were significant differences in learning and memory performance between participants showing a higher degree of modulation (>1 SD above mean) compared to participants showing a lower degree of modulation. No significant associations were found between VEP-plasticity and other neurocognitive domains. CONCLUSIONS: The current results suggest that LTP-like plasticity indexed by VEP modulation reflect processes specific to learning and memory. Future research is needed to further delineate the complex relationship between neural plasticity and learning and memory, specifically concerning possible clinical implications in populations with deficits in learning and memory function.