The visual physiology of the wild type mouse determined with pattern VEPs

Longitudinal Measures of Visual Function, Tumor Volume, and Prediction of Visual Outcomes after Treatment of Optic Pathway Gliomas

Visual evoked potentials (VEPs) were recorded of 60 infants and children with cerebral blindness, aged between six weeks and 10 years, and compared with age-matched normative data. Every patient had abnormal VEPs. 18 had absent flash and pattern VEPs and 13 had atypical or atypical and asymmetrical flash and pattern VEPs. Of the remaining 29, most had greater abnormality of pattern than of flash VEPs and greater abnormalities over parietal and temporal than occipital areas. Eight patients had normal occipital responses to flash and five others had delayed responses with normal morphology. One had normal occipital responses to pattern stimuli. All of these had abnormal late occipital responses or abnormal responses over the parietal and temporal areas. It is recommended that visual assessments using VEPs employ both flash and pattern stimuli, that pre-occipital as well as occipital recordings be made and that tracings be compared with age-specific normative data.

In kidney transplant recipients (KTRs), uraemia-induced central nervous system damage partly subsides, while the long-lasting exposure to tacrolimus may cause pathologic visual evoked potentials (VEP) findings, which have not been investigated yet. Thus, the aim of the present study was to assess the effect of tacrolimus maintenance treatment on bioelectrical function of optic nerves in stable KTRs. Sixty-five stable KTRs were enrolled, including 30 patients treated with twice-daily (Prograf) and 35 patients treated with prolonged once-daily (Advagraf) tacrolimus formulation. In all patients, pattern and flash VEP measurements were performed. Tacrolimus dosing and exposure were also analyzed. Overall, 129 eyes were analyzed. In pattern VEP, both (1°) and (15′) latencies of P100 waves were significantly longer, whereas (1°) and (15′) amplitudes were lower in the Advagraf group as compared with the Prograf group. Multivariate regression analyses revealed that the use of Advagraf (vs. Prograf) was independently associated with longer (1°) and (15′) P100 latencies and lower corresponding amplitudes, whereas log tacrolimus daily dose was only related to amplitudes in a whole study group. In flash VEP, log tacrolimus trough level was associated with negative changes in P2 wave amplitude irrespective of tacrolimus formulation, whereas its association with P2 latency was observed only in the Prograf group. Both the type of tacrolimus formulation and drug exposure influenced the VEP parameters in stable KTRs.

The diagnostic application of averaged visual evoked potentials (VEPs) is illustrated in the investigation of hysterical amblyopia and multiple sclerosis. Averaged VEPs elicited either by a flash of light or a presentation of a grating lasting 100 ms were recorded from the occiput of patients. All the VEPs in hysterical amblyopia were normal. In multiple sclerosis the flash VEPs looked normal for both eyes, whereas the VEPs elicited by grating (2 and 5 c/deg) showed an increase in the latency of the first positive wave, again for both eyes. After physical exercise the VEPs from the right eye were dramatically reduced in amplitude (Uhthoff's sign).

Transgenic mice overexpressing bcl-2, due to inhibition of naturally occurring cell death, have much larger brains and optic nerves as compared to wild-type mice. Since developmental cell death is believed to exert a crucial role in establishing the mature neural circuitry and function, we asked the question of whether basic aspects of vision were altered in bcl-2 mice. Local visually evoked potentials (VEPs) in response to patterned stimuli were recorded from the primary visual cortex. The representation of the vertical meridian was displaced by about 15% in the bcl-2 mouse, accounting for brain expansion. However, visual acuity, contrast threshold, and response latency were normal, indicating that compensatory mechanisms can ensure normal basic properties of vision in spite of marked neuronal redundancy.

Visually evoked potentials (VEPs) have been recorded from the Wulst surface of the little owl, Athene noctua, in response to counterphase-reversal of sinusoidal gratings with different contrast, spatial frequency and mean luminance, presented either monocularly or binocularly. Monocular full-field stimuli presented to either eye evoked VEPs of similar amplitude, waveform and latency. Under binocular viewing, VEPs approximately doubled in amplitude without waveform changes. VEPs with similar characteristics could be obtained in response to stimulation of the contralateral, but not ipsilateral, hemifield. These results suggest that a 50% recrossing occurs in thalamic efferents and that different ipsilateral and contralateral regions converge onto the same Wulst sites. The VEP amplitude progressively decreased with increase of the spatial frequency beyond 2 cycles/degree, and the high spatial frequency cut-off (VEP acuity) was under binocular viewing (8 cycles/degree) higher than under monocular (5 cycles/degree) viewing (200 cd/m2, 45% contrast). The VEP acuity increased with increase in the contrast and decreased with reduction of the mean luminance. The binocular gain in both VEP amplitude and VEP acuity was largest at the lowest luminance levels. Binocular VEP summation occurred in the medium-high contrast range. With decreased contrast, both monocular and binocular VEPs progressively decreased in amplitude and tended to the same contrast threshold. The VEP contrast threshold depended on the spatial frequency (0.6-1.8% in the range 0.12-2 cycles/degree). Binocular VEPs often showed facilitatory interaction (binocular/monocular amplitude ratio greater than 2), but the binocular VEP amplitude did not change either by changing the stimulus orientation (horizontal vs. vertical gratings) or by inducing different retinal disparities.(ABSTRACT TRUNCATED AT 250 WORDS)

BackgroundMigraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers.MethodsTwenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups.ResultsThe mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann’s areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers.ConclusionThis study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology.This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata.

Visual evoked potentials (VEPs) are widely used to objectively assess visual system function in animal models of ophthalmological diseases. Although use of chronically implanted electrodes is common in longitudinal VEP studies using rodent models, reliability of recordings over time has not been assessed. We compared VEPs 1 and 7 days after electrode implantation in the adult mouse. We also examined stimulus-independent changes over time, by assessing electroencephalogram (EEG) power and approximate entropy of the EEG signal. Stainless steel screws (600-μm diameter) were implanted into the skull overlying the right visual cortex and the orbitofrontal cortex of adult mice (C57Bl/6J, n = 7). Animals were reanesthetized 1 and 7 days after implantation to record VEP responses (flashed gratings) and EEG activity. Brain sections were stained for glial activation (GFAP) and cell death (TUNEL). Reliability analysis, using intraclass correlation coefficients, showed VEP recordings had high reliability within the same session, regardless of time after electrode implantation and peak latencies and approximate entropy of the EEG did not change significantly with time. However, there was poorer reliability between recordings obtained on different days, and a significant decrease in VEP amplitudes and EEG power. This amplitude decrease could be normalized by scaling to EEG power (within-subjects). Furthermore, glial activation was present at both time points but there was no evidence of cell death. These results indicate that VEP responses can be reliably recorded even after a relatively short recovery period but decrease response peak amplitude over time. Although scaling the VEP trace to EEG power normalized this decrease, our results highlight that time-dependent cortical excitability changes are an important consideration in longitudinal VEP studies. This study shows changes in VEP characteristics over time in chronically implanted mice. Thus, future preclinical longitudinal studies should consider time in addition to amplitude and latency when designing and interpreting research.

Due to the proximity of craniopharyngioma to the optic apparatus, one of the most common complications after surgery is visual deterioration. Intraoperative visual evoked potential (VEP), as a means of real-time visual function monitoring, has been integrated into transsphenoidal surgery for pituitary adenoma to predict postoperative visual outcome. Compared with pituitary tumor, craniopharyngioma often adheres to optic nerves, with increased risk of postoperative visual impairment. Furthermore, extended endoscopic endonasal surgery (EEES) can provide direct visualization of the surgical plane between the craniopharyngioma and the optic nerves, which contributes to analysis of the mechanism of real-time VEP changes during surgery. Therefore, VEP monitoring applied during EEES for craniopharyngioma may have more clinical value. However, only 9 patients who underwent EEES with VEP monitoring for craniopharyngioma have been sporadically reported to date. In this paper, the authors present the largest series to date analyzing the clinical value of VEP to predict postoperative visual outcome in adult patients with craniopharyngioma. Sixty-five adult patients who underwent EEES with intraoperative VEP monitoring for primary craniopharyngioma were retrospectively reviewed. The association between changes in VEP amplitude and postoperative visual outcome was determined. In addition, other potential prognostic factors with regard to postoperative visual outcomes were included in the analysis. Gross-total resection was achieved in 59 patients (90.8%). Reproducible and stable VEP was recorded in 128 of 130 eyes (98.5%). During surgery, VEP remained stable in 108 eyes, 10 (9.3%) of which had new visual acuity (VA) and/or visual field (VF) defects after surgery. Transient VEP decrease was recorded in 15 eyes, 4 (26.7%) of which had visual deterioration. Of the 5 eyes with permanent VEP decrease, 3 (60%) experienced postoperative visual impairment. Permanent VEP decrease (OR 19.868, p = 0.007) and tight adhesion (OR 6.104, p = 0.040) were independent adverse factors for postoperative VA deterioration. Tight adhesion (OR 7.150, p = 0.002) and larger tumor volume (OR 1.066, p = 0.001) were significant risk factors for postoperative VF defects. Intraoperative VEP monitoring can serve as a real-time warning to guide surgeons to avoid postoperative visual impairment. It effectively predicted VA changes in adult patients with craniopharyngioma after EEES. Tight adhesion and larger tumor volume were also strong predictors of postoperative visual impairment.

Objective: To examine the association of visual evoked potential (VEP) latency and high-contrast visual acuity (VA) with cognitive function in MS patients using a standardized computerized battery. Background Cognition and vision are now recognized as important domains for clinical trials assessment in MS. The correlation of VEP conduction delay and VA with cognitive impairment has not been described. Design/Methods: Participants received a VEP evaluation as well as a Snellen vision test and completed a standardized, validated MindStreams battery designed to detect mild impairment (NeuroTrax Corp., NY) in their primary language. VEP latency categories were: normal =113 and =130 and =150 and 170 msec. Results: Among MS patients (n=435, 870 eyes), Accounting for age, disease duration, and within-patient, inter-eye correlations, abnormal VEP latency was associated with poorer overall battery performance (Global Cognitive Score, p Conclusions: Abnormal VEP latency and high-contrast VA in patients with MS may be associated with reduced cognitive function, particularly in domains related to executive function. Longer VEP latency may be particularly related to poorer visual spatial processing. Further studies will examine the role of afferent visual dysfunction and retinal axonal and neuronal loss in the relation of VEP latency to cognitive impairment and work disability in MS cohorts. Disclosure: Dr. Chahin has nothing to disclose. Dr. Balcer has received personal compensation for activities with Biogen Idec, Vaccinex and Bayer as a consultant and has received honoraria from Biogen Idec and Novartis. Dr. Zarif has received personal compensation for activities with Biogen Idec as a consultant. Ms. Bumstead has received personal compenstion for activities with Biogen Idec and Teva Neuroscience as a consultant. Dr. Fafard has nothing to disclose. Dr. Mebrahtu has nothing to disclose. Dr. Galetta has received personal compensation for activities with Biogen Idec Teva, and Novartis as a speaker.Dr. Galetta has received research support from Biogen Idec. Dr. Doniger has received personal compensation for activities with NeuroTrax Corporation as an employee. Dr. Gudesblatt has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Lundbeck Research USA, Inc. and Medtronic as a consultant.

Chapter 34 - Visually evoked potentials

Visual evoked potentials (VEP)were recorded in a large normal population. Significant age differences were found, and the P2 component (latency 116 m.sec.) was the most consistent component of the VEP both between and within the individuals. The validity of the normal VEP criteria were tested in two groups of patients with known visual field defects. One group with central lesions and hemianopia, and a second with senile macula degeneration. The VEP varied with the degree of visual impairment with low amplitudes, long latencies and no localization at either occiput being consistent with poor acuity. The P2 component appeared to be particularly effected by the loss of central retinal function. Two prospective studies were carried out on patients with dense opacities of the optic media. One group of patients had unilateral longstanding cataracts, the second group had recently sustained severe eye injuries with penetration of the globe. The VEP was graded to predict a good visual recovery or no useful function remaining and the gradings were significantly correlated with the final visual outcome. It was concluded that the flash VEP is particularly useful to monitor visual function with dense opacities of the optic media if there is damage to the central retina or visual pathways and cortex.

Electrophysiological and morphological findings were studied in a case of acute zonal occult outer retinopathy (AZOOR) showing abnormal pattern visual evoked potentials (VEPs) at the onset and significant functional recovery in the natural course. A 21-year-old woman presented with acute onset of photopsia and a large scotoma in the right eye of 2 weeks duration. Her visual acuity was 20/20 in both eyes with no ophthalmoscopic and fluorescein angiographic abnormalities. However, a relative afferent pupillary defect and an enlarged blind spot were found in the right eye. The pattern VEPs were severely reduced when the right eye was stimulated. The amplitudes of both rod and cone full-field electroretinographics (ERGs) were reduced in the right eye. The amplitudes of the multifocal ERGs were reduced in the area of the enlarged blind spot. Irregularities in the inner segment/outer segment (IS/OS) line of the photoreceptors were observed over the nasal fovea by optical coherence tomography (OCT). The patient was followed without treatment. The enlarged blind spot disappeared in 3 months after the onset. At 5 months, reappearance of the IS/OS line was detected by OCT. At 6 months, the P100 recovered to normal values. At 1 year, the reduced full-field ERGs were almost normal size and the multifocal ERGs in the area corresponding to the enlarged blind spot were also improved. ERG findings are crucial for differentiating AZOOR from retrobulbar neuritis, especially in patients with abnormal pattern VEPs. The pattern VEPs, full-field ERGs, multifocal ERGs, and OCT images can be abnormal in the early phase of AZOOR, but they can all improve during the natural course.

Achiasmia is a rarely diagnosed visual pathway maldevelopment where all or the majority of nasal retinal fibres fail to decussate at the optic chiasm. It has been identified by neuroimaging and also by visual evoked potential (VEP) asymmetry. VEP asymmetry has not been defined consistently in previous studies. The aim was to study VEP asymmetry to flash stimulation in two children with maldevelopment of the optic chiasm in comparison to control children. Both children had congenital nystagmus, optic nerve hypoplasia with a bilateral small double ring, bitemporal visual field defect and normal colour vision. In child 1 visual acuity in both eyes was 0.1, in child 2 it was 0.2. MRI showed reduced chiasmal size in child 1, while in child 2 it was combined with other midline abnormalities. VEP to monocular flash stimulation showed in both children distinctive occipital distribution, which was not observed in control children. The N2 wave was distributed asymmetrically over the ipsilateral hemisphere to the stimulated eye, while the P2 wave was distributed over both hemispheres. The P2 wave was however better defined over the ipsilateral hemisphere. Flash VEP occipital distribution remained similar in child 1, who was followed from 10 months to 9 years. These cases of achiasmia demonstrate a distinctive VEP asymmetry in the distribution of the flash VEP N2 wave, as well as the expected structural defect determined by neuroimaging.

We compared the diagnostic power of electrophysiologically and psychophysically measured contrast thresholds for the diagnosis of glaucoma. Additionally, we investigated whether combining results from the two methods improved diagnostic power. Seven-eight subjects between 40 and 88 years formed the main study group: 21 normal controls (9 males) and 57 glaucoma patients (30 males) were tested. Twenty-two younger control subjects were also tested. Contrast thresholds were determined for a 1 cpd sinusoidal grating, subtending 41° × 52° modulated at 14.3 rps. The thresholds were based on the same staircase method applied to visual evoked potential (VEP) and psychophysical responses (Psyc). Diagnostic power was assessed by the percent area under the curve (%AUC) of receiver operating characteristic plots. Psyc showed significant age dependence, -0.10 ± 0.02 dB, while VEPs did not. Diagnostic performance for moderate and severe eyes combined was modest: Psyc 74 ± 9.0 % and VEP 72 ± 9.1 %, but improved significantly (p < 0.05) for a simple combined method, up to 90 ± 6.0 % for moderate disease. The combined method improved %AUC for all severities on average (p < 0.03). Canonical correlation analysis indicated that the four threshold measures contained independent information and that these independent dimensions were each correlated with glaucoma severity (p < 0.0015). Combining the VEP and Psyc thresholds appeared to improve diagnostic power. Canonical correlation analysis indicated that they measured statistically independent aspects of glaucoma possibly related to disease severity. Adding the 20-s psychophysical test to a VEP test produced a significant benefit for a small time cost.