Multifocal Visual Evoked Potential Research Articles

Mechanical-scan-free multicolor super-resolution imaging with diffractive spot array illumination.

Point-scanning microscopy approaches are transforming super-resolution imaging. Despite achieving parallel high-speed imaging using multifocal techniques, efficient multicolor imaging methods with high-quality illumination are currently lacking. In this paper, we present for the first time Mechanical-scan-free multiColor Super-resolution Microscopy (MCoSM) with spot array illumination, which enables mechanical-scan-free super-resolution imaging with adjustable resolution and a good effective field-of-view based on spatial light modulators. Through 100-2,500 s super-resolution spot illumination with different effective fields of view for imaging, we demonstrate the adjustable capacity of MCoSM. MCoSM extends existing spectral imaging capabilities through a time-sharing process involving different color illumination with phase-shift scanning while retaining the spatial flexibility of super-resolution imaging with diffractive spot array illumination. To demonstrate the prospects of MCoSM, we perform four-color imaging of fluorescent beads at high resolution. MCoSM provides a versatile platform for studying molecular interactions in complex samples at the nanoscale level.

Visual cortical area contributions to the transient, multifocal and steady-state VEP: A forward model-informed analysis

Abstract Central to our understanding of how visual-evoked potentials (VEPs) contribute to visual processing is the question of where their anatomical sources are. Three well-established measures of low-level visual cortical activity are widely used: the first component (“C1”) of the transient and multifocal VEP, and the steady-state VEP (SSVEP). Although primary visual cortex (V1) activity has often been implicated in the generation of all three signals, their dominant sources remain uncertain due to the limited resolution and methodological heterogeneity of source modelling. Here, we provide the first characterisation of all three signals in one analytic framework centred on the “cruciform model”, which describes how scalp topographies of V1 activity vary with stimulus location due to the retinotopy and unique folding pattern of V1. We measured the transient C1, multifocal C1, and SSVEPs driven by an 18.75 Hz and 7.5 Hz flicker, and regressed them against forward models of areas V1, V2, and V3 generated from the Benson-2014 retinotopy atlas. The topographic variations of all four VEP signals across the visual field were better captured by V1 models, explaining between 2 and 6 times more variance than V2/V3. Models with all three visual areas improved fit further, but complementary analyses of temporal dynamics across all three signals indicated that the bulk of extrastriate contributions occur considerably later than V1. Overall, our data support the use of peak C1 amplitude and SSVEPs to probe V1 activity, although the SSVEP contains stronger extrastriate contributions. Moreover, we provide elaborated heuristics to distinguish visual areas in VEP data based on signal lateralisation as well as polarity inversion.

Visual Evoked Potential After Levodopa in Amblyopic Eyes

Purpose to study the clinical and electrophysiological changes after Levodopa in amblyopic eyes. Methods: Fifty patients with amblyopia (20 hypermetropic anisometropia and 20 myopic anisometropic amblyopia,10 astigmatic amblyopic) were included in this study, Levodopa was administered daily for 6 weeks associated with occlusion therapy and visual training. The drug was stopped and patients continued on occlusion therapy associated with visual training for another 6 weeks. Then gradual reduction of occlusion time and visual training was performed for another 6 weeks, and finally all treatments were stopped for 6 weeks. Visual acuity and visual evoked potentials (VEP), including both multifocal VEP (MFVEP) and Pattern VEP (PVEP) were recorded before the treatment, at 1,6,12,18,24weeks after beginning of treatment. Results: Significant improvement of visual acuity (mean 0.50), with stabilization at the end of the 6th week associated with improved PVEP and MFVEP parameters was reported. Stabilization of the visual improvement after stoppage the treatment without any deterioration of vision or VEP parameters. Conclusion: Improved visual acuity with stabilization can be achieved with combined Levodopa, occlusion and visual training therapy confirmed with VEP improvement.

Optic neuritis: aetiopathogenesis, diagnosis, prognosis and management

The main causes of optic neuritis (ON) are multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease, also known as MOGAD. When all screening is negative, we can speak of idiopathic ON, although this diagnosis should be provisional. ON can be diagnosed clinically and paraclinical tests are not routinely required to confirm it. However, tests such as magnetic resonance imaging (MRI), visual evoked potentials (VEP) and optical coherence tomography (OCT) can lend support to the diagnosis if the clinical presentation is atypical. The use of new MRI sequences, OCT, multifocal VEPs and the determination of neurofilaments has allowed ON to be used as a model for remyelination and neuroprotection, leading to phase II clinical trials. Some of these drugs, such as opicinumab, clemastine, phenytoin or simvastatin, have shown positive results; however, their clinical effect remains to be defined. It is accepted that corticosteroids do not improve the long-term prognosis of ON, although some retrospective studies suggest that there is a therapeutic window from the onset of symptoms. Plasmapheresis has also been shown to be effective in patients with ON. In this review we will address basic aspects of the management of ON, in the fundamental context of MS, NMOSD and MOGAD, with emphasis on etiopathogenic, diagnostic, prognostic and therapeutic developments.

Using advanced analysis of multifocal visual-evoked potentials to evaluate the risk of clinical progression in patients with radiologically isolated syndrome

This study aimed to assess the role of multifocal visual-evoked potentials (mfVEPs) as a guiding factor for clinical conversion of radiologically isolated syndrome (RIS). We longitudinally followed a cohort of 15 patients diagnosed with RIS. All subjects underwent thorough ophthalmological, neurological and imaging examinations. The mfVEP signals were analysed to obtain features in the time domain (SNRmin: amplitude, Latmax: monocular latency) and in the continuous wavelet transform (CWT) domain (bmax: instant in which the CWT function maximum appears, Nmax: number of CWT function maximums). The best features were used as inputs to a RUSBoost boosting-based sampling algorithm to improve the mfVEP diagnostic performance. Five of the 15 patients developed an objective clinical symptom consistent with an inflammatory demyelinating central nervous system syndrome during follow-up (mean time: 13.40 months). The (SNRmin) variable decreased significantly in the group that converted (2.74 ± 0.92 vs. 4.07 ± 0.95, p = 0.01). Similarly, the (bmax) feature increased significantly in RIS patients who converted (169.44 ± 24.81 vs. 139.03 ± 11.95 (ms), p = 0.02). The area under the curve analysis produced SNRmin and bmax values of 0.92 and 0.88, respectively. These results provide a set of new mfVEP features that can be potentially useful for predicting prognosis in RIS patients.

Predictive value of optical coherence tomography, multifocal visual evoked potentials, and full-field visual evoked potentials of the fellow, non-symptomatic eye for subsequent multiple sclerosis development in patients with acute optic neuritis

Background: Diagnosis of multiple sclerosis (MS) may sometimes be ascertained at the time of optic neuritis (ON) but other times require the advent of new disease activity. Objectives: The aim of this study was to examine the predictive value of optical coherence tomography (OCT) and visual evoked potential (VEP) measurements of the non-symptomatic, fellow eye of ON patients, for conversion to MS. Methods: This is a prospective cohort study in patients with acute ON. OCT thickness measurements of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer–inner plexiform layer (GCLIPL), and multifocal (mf) VEP and full-field (ff) VEP, were performed. Univariate and multivariate Cox regression examined the value of predictors for the conversion to MS. Results: A total of 79 unilateral, acute ON patients, with no MS diagnosis or prior demyelination, were included. Of which, 28 patients developed MS during follow-up. Inferonasal GCLIPL, mean GCLIPL, and pRNFL thickness significantly predicted MS development in multivariate analysis (hazard ratio (HR) = 0.922–0.939, p = 0.0172–0.021). MfVEP mean latency (HR = 1.052, p = 0.006) only predicted MS conversion in univariate analysis. No significant predictive value was shown for the other parameters (p > 0.2). Conclusion: While both mfVEP and OCT are useful tools in the evaluation of acute ON patients, only OCT measurements of fellow eyes may serve as an independent predictor of MS development.

Identification of clusters in multifocal electrophysiology recordings to maximize discriminant capacity (patients vs. control subjects)

PurposeTo propose a new method of identifying clusters in multifocal electrophysiology (multifocal electroretinogram: mfERG; multifocal visual-evoked potential: mfVEP) that conserve the maximum capacity to discriminate between patients and control subjects.MethodsThe theoretical framework proposed creates arbitrary N-size clusters of sectors. The capacity to discriminate between patients and control subjects is assessed by analysing the area under the receiver operator characteristic curve (AUC). As proof of concept, the method is validated using mfERG recordings taken from both eyes of control subjects (n = 6) and from patients with multiple sclerosis (n = 15).ResultsConsidering the amplitude of wave P1 as the analysis parameter, the maximum value of AUC = 0.7042 is obtained with N = 9 sectors. Taking into account the AUC of the amplitudes and latencies of waves N1 and P1, the maximum value of the AUC = 0.6917 with N = 8 clustered sectors. The greatest discriminant capacity is obtained by analysing the latency of wave P1: AUC = 0.8854 with a cluster of N = 12 sectors.ConclusionThis paper demonstrates the effectiveness of a method able to determine the arbitrary clustering of multifocal responses that possesses the greatest capacity to discriminate between control subjects and patients when applied to the visual field of mfERG or mfVEP recordings. The method may prove helpful in diagnosing any disease that is identifiable in patients’ mfERG or mfVEP recordings and is extensible to other clinical tests, such as optical coherence tomography.

A computer-aided diagnosis of multiple sclerosis based on mfVEP recordings.

IntroductionThe aim of this study is to develop a computer-aided diagnosis system to identify subjects at differing stages of development of multiple sclerosis (MS) using multifocal visual-evoked potentials (mfVEPs). Using an automatic classifier, diagnosis is performed first on the eyes and then on the subjects.PatientsMfVEP signals were obtained from patients with Radiologically Isolated Syndrome (RIS) (n = 30 eyes), patients with Clinically Isolated Syndrome (CIS) (n = 62 eyes), patients with definite MS (n = 56 eyes) and 22 control subjects (n = 44 eyes). The CIS and MS groups were divided into two subgroups: those with eyes affected by optic neuritis (ON) and those without (non-ON).MethodsFor individual eye diagnosis, a feature vector was formed with information about the intensity, latency and singular values of the mfVEP signals. A flat multiclass classifier (FMC) and a hierarchical classifier (HC) were tested and both were implemented using the k-Nearest Neighbour (k-NN) algorithm. The output of the best eye classifier was used to classify the subjects. In the event of divergence, the eye with the best mfVEP recording was selected.ResultsIn the eye classifier, the HC performed better than the FMC (accuracy = 0.74 and extended Matthew Correlation Coefficient (MCC) = 0.68). In the subject classification, accuracy = 0.95 and MCC = 0.93, confirming that it may be a promising tool for MS diagnosis.ConclusionIn addition to amplitude (axonal loss) and latency (demyelination), it has shown that the singular values of the mfVEP signals provide discriminatory information that may be used to identify subjects with differing degrees of the disease.

Age Related Decline in Cortical Multifocal Flash VEP: Latency Increases Shown to Be Predominately Magnocellular.

As the visual system ages, flicker sensitivity decreases and the latencies of cortical visual evoked potentials (VEP) increase. However, the extent to which these effects reflect age-related changes in the magnocellular (M) and or parvocellular (P) pathways remain unclear. Here, we investigated the relation between flicker fusion frequencies and VEP non-linearities induced by rapid stimulation, as a function of age over 6 decades. The approach, using Wiener kernel analysis of multifocal flash (mf)VEP, allows the extraction of signatures of both M and P processing and hence establishing a neural basis of the known decline in flicker fusion threshold. We predicted that, in a sample of 86 participants, age would be associated with a latency increase in early mfVEP response components and that flicker fusion thresholds, for both low and high contrast stimuli, would relate to the temporal efficiency of the M-generated VEP component amplitudes. As expected, flicker fusion frequency reduced with age, while latencies of early second order peaks of the mfVEP increased with age, but M temporal efficiency (amplitude ratio of first to second order peaks) was not strongly age-related. The steepest increases in latency were associated with the M dominated K2.1 (second order first slice) N70 components recorded at low and high contrast (6.7 and 5.9 ms/decade, respectively). Interestingly, significant age-related latency shifts were not observed in the first order responses. Significant decreases in amplitude were found in multiple first and second order components up to 30 years of age, after which they remained relatively constant. Thus, aging and decline in visual function appears to be most closely related to the response latencies of non-linearities generated by the M pathway.

Coding Prony\u2019s method in MATLAB and applying it to biomedical signal filtering

BackgroundThe response of many biomedical systems can be modelled using a linear combination of damped exponential functions. The approximation parameters, based on equally spaced samples, can be obtained using Prony’s method and its variants (e.g. the matrix pencil method). This paper provides a tutorial on the main polynomial Prony and matrix pencil methods and their implementation in MATLAB and analyses how they perform with synthetic and multifocal visual-evoked potential (mfVEP) signals.This paper briefly describes the theoretical basis of four polynomial Prony approximation methods: classic, least squares (LS), total least squares (TLS) and matrix pencil method (MPM). In each of these cases, implementation uses general MATLAB functions. The features of the various options are tested by approximating a set of synthetic mathematical functions and evaluating filtering performance in the Prony domain when applied to mfVEP signals to improve diagnosis of patients with multiple sclerosis (MS).ResultsThe code implemented does not achieve 100%-correct signal approximation and, of the methods tested, LS and MPM perform best. When filtering mfVEP records in the Prony domain, the value of the area under the receiver-operating-characteristic (ROC) curve is 0.7055 compared with 0.6538 obtained with the usual filtering method used for this type of signal (discrete Fourier transform low-pass filter with a cut-off frequency of 35 Hz).ConclusionsThis paper reviews Prony’s method in relation to signal filtering and approximation, provides the MATLAB code needed to implement the classic, LS, TLS and MPM methods, and tests their performance in biomedical signal filtering and function approximation. It emphasizes the importance of improving the computational methods used to implement the various methods described above.

Reaching Beyond the Retina with Clinical Electrophysiology

Electrophysiological recordings from the retina and cortex are pivotal to reach beyond the retina for ophthalmological and neuro-ophthalmological diagnostic testing. Pattern electroretinograms (PERG) can be used to examine retinal ganglia cells and visual evoked potentials (VEP) help to investigate overall visual pathways. Thus, they support objective functional tests of visual pathways, as well as differential diagnosis. Conventional electrophysiology is of limited value in detecting local defects in the visual field. This gap is filled by applications of multifocal electrophysiology. This permits spatially resolved testing with multifocal PERG (mfPERG) and multifocal VEP (mfVEP), and eventually objective visual field testing with mfVEP. It is important for this spectrum of methods to consider possible confounds when performing the measurements and when interpreting the results. This is explained in the present article on the basis of a series of typical examples.

Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential.

BackgroundMultifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies.ObjectiveMF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants.MethodsThis exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24.ResultsA trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was − 17.57 and − 31.41 nanovolts (nV) in placebo but only − 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively].ConclusionResults from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment.RegistrationClinicalTrials.gov identifier NCT01721161.

Visual Evoked Potentials and Glaucoma.

Visual evoked potentials (VEP) can be used to assess the function of the visual system objectively. Research on VEP testing as a method of glaucoma evaluation has been performed for many years. Pattern VEP has shown good specificity and sensitivity in the detection of glaucoma in some studies, but other studies have not shown similar efficacy. Multifocal VEP can produce a topographical measure of glaucomatous damage and has been shown to be able to detect a similar number of defects in patients with glaucoma or ocular hypertension as compared with the visual field test. Despite promising data on these VEP test modalities in the assessment of glaucoma, multiple aspects of test administration make their routine use impractical in a clinical setting. New VEP testing modalities, such as short-duration transient VEP and isolated-check VEP, allow the test to be performed more quickly and easily. Further research on these more recent technologies may allow us to use VEP effectively in the diagnosis and management of glaucoma.

Effects of Stimulus Size and Contrast on the Initial Primary Visual Cortical Response in Humans.

Decades of intracranial electrophysiological investigation into the primary visual cortex (V1) have produced many fundamental insights into the computations carried out in low-level visual circuits of the brain. Some of the most important work has been simply concerned with the precise measurement of neural response variations as a function of elementary stimulus attributes such as contrast and size. Surprisingly, such simple but fundamental characterization of V1 responses has not been carried out in human electrophysiology. Here we report such a detailed characterization for the initial "C1" component of the scalp-recorded visual evoked potential (VEP). The C1 is known to be dominantly generated by initial afferent activation in V1, but is difficult to record reliably due to interindividual anatomical variability. We used pattern-pulse multifocal VEP mapping to identify a stimulus position that activates the left lower calcarine bank in each individual, and afterwards measured robust negative C1s over posterior midline scalp to gratings presented sequentially at that location. We found clear and systematic increases in C1 peak amplitude and decreases in peak latency with increasing size as well as with increasing contrast. With a sample of 15 subjects and ~180 trials per condition, reliable C1 amplitudes of -0.46µV were evoked at as low a contrast as 3.13% and as large as -4.82µV at 100% contrast, using stimuli of 3.33° diameter. A practical implication is that by placing sufficiently-sized stimuli to target favorable calcarine cortical loci, robust V1 responses can be measured at contrasts close to perceptual thresholds, which could greatly facilitate principled studies of early visual perception and attention.

Optic neuritis as a phase 2 paradigm for neuroprotection therapies of multiple sclerosis: update on current trials and perspectives.

In multiple sclerosis as the most common inflammatory demyelinating disease in Western countries, major therapeutic success has been achieved with regard to strategies targeting immunological master switches. These approaches effectively reduce inflammatory disease activity but fail to address ongoing neurodegeneration or disturbed regeneration. However, intense research efforts investigating molecular mechanisms of disease have identified 'druggable' targets for prevention of inflammatory neurodegeneration and disturbed regeneration. This review covers recent developments in clinical trials using optic neuritis as a model for screening such neuroprotective and neuroregenerative therapeutic approaches. Optic neuritis has been used in a series of recent pilot studies investigating the effects of erythropoietin, simvastatin, autologous mesenchymal stem cells, phenytoin, as well as blockade of LINGO-1 (opicinumab). Of note, these studies applied novel outcome measures related to function and structure of the visual pathway, including optical coherence tomography, full-field visual-evoked potentials, multifocal visual-evoked potential, high as well as low-contrast visual acuity. Comparison of these different approaches reveals novel insights into short-term evolution of neurobiological effects during optic neuritis and the window of opportunity for therapeutic interventions. Translation of neuroprotective and neuroregenerative approaches to clinical reality represents a huge challenge. Optic neuritis as a prototypic autoimmune demyelinating disease offers an option for testing new therapies targeting key deleterious processes in multiple sclerosis.

Effects of Photobiomodulation Therapy on Patients with Primary Open Angle Glaucoma: A Pilot Study.

The purpose of this work was to study the safety of photobiomodulation therapy in patients with primary open angle glaucoma (POAG). Therapeutic options for POAG focus on lowering the intraocular pressure (IOP) but cannot stop disease progression to irreversible damages. The study was designed as a controlled, single-blinded, interventional case series (38 patients; 63 eyes). Low-level laser therapy was performed once or twice per week using a continuous wave (CW) diode laser (780 nm; 10 mW; 292 Hz modulation; 3 mm(2) beam spot). The limbus area was circularly irradiated for 30 sec (0.3 W/cm(2); 10 J/cm(2)) at a 1 cm distance. Additional parts of the bulbus were irradiated for 90 sec (30 J/cm(2)) pointing the beam toward retinal areas corresponding to defective visual fields. A control group of 10 patients (20 eyes) received mock treatment. Visual acuity was assessed using Snellen projection optotypes. IOP was determined by applanation tonometry. Visual fields were determined by kinetic Goldmann perimetry. Multifocal visual evoked potential (M-VEP) was recorded in 15 patients (30 eyes). Poor visual acuity (≤ 20/25), initially found in 24 of 63 eyes (38.1%), improved in 17 (70.8%) eyes and did not change in 7 eyes (29.2%). Mean IOP dropped from 24.9 ± 14.9 to 15.0 ± 6.5 mm Hg (-39.7%, p < 0.001). Visual fields were either fully restored, improved by at least 10 degrees, or remained unchanged in 32, 29, and 2 of 63 eyes (51%, 46%, and 3%), respectively. Mean M-VEP latency was reduced by 13.5 msec (-8%, p < 0.001); mean amplitude increased by +677 nV (+14%, p < 0.001). Adverse effects were not observed. No changes were noted in control eyes. This first small series of cases indicated that photobiomodulation might be a safe approach to lower IOP and to improve visual acuity and fields in eyes with POAG.

Visual Pathways in Humans With Ephrin-B1 Deficiency Associated With the Cranio-Fronto-Nasal Syndrome.

Numerous animal studies demonstrated the importance of components of the ephrin/Eph system for correct visual system development. Analogous investigations in humans are entirely missing. Here, we examined the visual system in humans with ephrin-B1 deficiency, which is x-linked and associated with the cranio-fronto-nasal syndrome (CFNS) in heterozygous females. For one male hemizygous for ephrin-B1 deficiency and three affected heterozygous females with molecular-genetically confirmed mutations, the integrity of the partial decussation of the optic nerves was assessed with visual evoked potentials (VEPs) and compared with albinotic, achiasmic, and control participants with healthy vision. Further, retinal morphology and function and the gross-retinotopic representation of the primary visual cortex were examined with spectral-domain optical coherence tomography (SD-OCT), ERG, and multifocal (mf) VEPs for the male participant and part of the carriers. Strabismus and lack of stereovision was evident in the male and two of the females. Other characteristics of the visual system organization and function were normal: (1) retina: SD-OCT and funduscopy indicated normal foveal and optic nerve head morphology. Electroretinograms indicated normal retinal function, (2) optic chiasm: conventional (c)VEP showed no evidence for misrouting and mfVEPs were only suggestive of, if any, very minor local misrouting, and (3) visual cortex: mfVEP characteristics indicated normal retinotopic gross-representations of the contralateral visual hemifield in each hemisphere. While ephrin-B1 deficiency leads to abnormal visual pathways in mice, it leaves the human visual system, apart from deficits in binocular vision, largely normal. We presume that other components of the ephrin-system can substitute the lack of ephrin-B1 in humans.

Clinical value of electrophysiology in determining the diagnosis of visual dysfunction in neuro-ophthalmology patients.

To assess clinical value of visual electrophysiology in identifying causes of visual dysfunction in patients referred from neuro-ophthalmology clinics. A review of 410 subjects (aged 0.3-88 years) referred for visual electrophysiology from neuro-ophthalmologists between 2009 and 2013 was performed. Subjects were divided into those with unexplained poor vision, visual field defects, visual symptoms or other reasons (e.g. monitoring for drug toxicity or known conditions). Subjects underwent pattern, full-field and multifocal electroretinography (ERG) and pattern visual evoked potential (VEP) tests. Flash and multifocal VEP were included where indicated. Most subjects referred for poor vision (n = 158) had electrophysiology findings suggestive of retinopathy (37 %) or post-retinal pathology (34 %). Those with poorer vision (worse than 6/24) were more likely to have abnormal recordings (86 vs. 62 %, p = 0.002). Among subjects with unexplained visual field defects (n = 102), findings of retinopathy, post-retinal pathology and normal recordings were noted in 31, 24 and 28 %, respectively. Most subjects with other visual symptoms (n = 97) had normal findings (69 %). The multifocal ERG was most sensitive for detecting retinopathy (96 %) and maculopathy (95 %), while pattern VEP was most sensitive for post-retinal pathology (94 %). An indeterminate result was noted in 9 %. Electrophysiology was effective in differentiating between retinopathy, post-retinal pathology and normality in 91 % of subjects. Pre-testing provisional diagnoses of retinopathy and post-retinal pathology were revised in 30 and 42 %, respectively, after electrophysiology. Appreciation of characteristics of each test, correlation with the clinical picture and interpretation of results in totality are required to localize the site of pathology.

A signal-to-noise-ratio-based analysis of multifocal visual-evoked potentials in multiple sclerosis risk assessment

ObjectiveTo study the value of using the signal-to-noise ratio (SNR) of multifocal visual-evoked potentials (mfVEPs) in assessment of subjects at risk of developing multiple sclerosis (MS). MethodsMfVEP signals were obtained from 15 patients with radiologically isolated syndrome (RIS), from 28 patients with clinically isolated syndrome (CIS), from 28 with clinically definite MS and from 24 control subjects. The CIS and MS groups were divided into two subgroups: those with eyes affected by optic neuritis (ON) and those without (non-ON). The mfVEPs’ SNR was obtained for both the whole visual field and at various eccentric rings. The area under the curve (AUC) was calculated by comparing the control subjects’ mfVEP SNR values with those of the RIS, CIS and MS groups. ResultsIn whole visual field analysis, risk of developing MS increased as SNR decreased (SNRCONTROL=0.70, SNRRIS=0.62, SNRCIS-nonON=0.54, SNRCIS-ON=0.40, SNRMS-nonON=0.52, SNRMS-ON=0.40). Ring 5 (9.8°–15° eccentricity) was most affected by the SNR decrease, as indicated by its higher AUC values (AUCFULL_EYE=0.81, AUCRING_5=0.89). A significant relationship (Spearman correlation, ρRING_5=0.61) between SNR values and disability severity on the Expanded Disability Status Scale (EDSS) was observed in clinically definite MS patients. ConclusionA new method based on analysis of the SNR of mfVEP signal amplitude improves assessment of patients at risk of developing MS. SignificanceImproved mfVEP assessment of MS-risk patients was achieved by using SNR values at 9.8°–15° eccentricity of the visual field.

Mathematical impairment associated with high-contrast abnormalities in change detection and magnocellular visual evoked response.

The cause of developmental dyscalculia, a specific deficit in acquisition of arithmetic skills, particularly of enumeration, has never been investigated with respect to the patency of the visual magnocellular system. Here, the question of dysfunction of the afferent magnocellular cortical input and its dorsal stream projections was tested directly using nonlinear analysis of the visual evoked potential (VEP) and through the psychophysical ability to rapidly detect visual change. A group of young adults with self-reported deficiencies of arithmetical ability, showed marked impairment in magnitude estimation and enumeration performance-though not in lexical decision reaction times when compared with an arithmetically capable group controlled for age and handedness. Multifocal nonlinear VEPs were recorded at low (24 %) and high (96 %) contrast. First- and second-order VEP kernels were comparable between groups at low contrast, but not at high contrast. The mathematically impaired group showed an abnormal lack of contrast saturation in the shortest latency first-order peak (N60) and a delayed P100 positivity in the first slice of the second-order kernel. Both features have previously been argued to be physiological markers of magnocellular function. Mathematically impaired participants also performed worse on a gap paradigm change detection for digit task showing increased reaction times for high-contrast stimuli but not for low-contrast stimuli compared with controls. The VEP results give direct evidence of abnormality in the occipital processing of magnocellular information in those with mathematical impairment. The anomalous high visual contrast physiological and psychophysical performance suggests an abnormality in the inhibitory processes that normally result in saturation of contrast gain in the magnocellular system.