Clinical evaluation of VEPs to interleaved checkerboard reversal stimulation of central,hemi- and peripheral fields

The VEPs of 195 patients referred for supportive evidence of multiple sclerosis or optic neuritis were studied by a new method of interleaved checkerboard reversal stimulation of different areas of the visual field. In the first group of 95 patients checks of 40′ subtense reversed in the whole field (28° × 20°), alternately in the left and right hemifields and alternately in the central (5° radius) and peripheral fields. In the second group of 100 patients checks reversed in the whole field and in interleaved mode in 3 visual field areas, comprising the central (4° radius) and left and right hemisurround fields.In the first group abnormal responses were recorded from 52 eyes and there was partial disagreement among the stimulus conditions in 10 of the 52. Abnormalities were seen uniquely to central field stimulation in 3 eyes but never to whole field stimulation alone. In the second group abnormal responses were recorded in 58 eyes, again never uniquely to whole field stimulation, while abnormalities confined to one or two areas of the visual field were seen in 24, providing evidence of peripheral field involvement alone in 8 eyes.In the first group, waveforms created from the sum of the left and right hemifield and central and peripheral field responses showed quite close conformity to the whole field VEP, although amplitudes were significantly lower and latencies significantly shorter. In 7 eyes responses would have been differently classified (normal or abnormal) using the sum as compared with the whole fields. The sum of the 3 interleaved stimuli was less reliable, its morphology often not closely approximating whole field responses.It is suggested that interleaved stimulation of two or more areas of the visual field is a sensitive and reliable method which reduces the time necessary to perform the test and helps control the patients' concentration, fixation and alertness. Whole field stimulation is probably necessary only in patients with severely degraded responses.     

Effect of check size on the pattern reversal visual evoked potential

Modifications of the components of pattern-reversal visual evoked potentials (PR-VEP) with changes in check size of the stimulating pattern were studied in 11 healthy subjects. We made use of 8 different check size ranging between 10 and 90 min of arc. Changes in the check size modified in different manners the latencies and amplitudes of N75, P100 and N145. Two-step statistical analyses using the polynomial regression analysis method revealed significant modifications of latencies of the 3 components, but non-significant modifications of the amplitudes, except for N75. The latency and amplitude of N75 showed a significant inverse linear relationship with the logarithm of the check size, while the P100 and N145 latencies showed significant curvilinear relationships, with minimal latencies at check sizes around 35 min. These findings suggest different physiological properties of N75 from those of P100 and N145, and hence, the necessity to establish normal values for each check size of stimulation, for application in clinical studies.     

The tactile perception of stimulus orientation

Studies of the visual system suggest that, at an early stage of form processing, a stimulus is represented as a set of contours and that a critical feature of these local contours is their orientation. Here, we characterize the ability of human observers to identify or discriminate the orientation of bars and edges presented to the distal fingerpad. The experiments were performed using a 400-probe stimulator that allowed us to flexibly deliver stimuli across a wide range of conditions. Orientation thresholds, approximately 20 degrees on average, varied only slightly across modes of stimulus presentation (scanned or indented), stimulus amplitudes, scanning speeds, and different stimulus types (bars or edges). The tactile orientation acuity was found to be poorer than its visual counterpart for stimuli of similar aspect ratio, contrast, and size. This result stands in contrast to the equivalent spatial acuity of the two systems (at the limit set by peripheral innervation density) and to the results of studies of tactile and visual letter recognition, which show that the two modalities yield comparable performance when stimuli are scaled appropriately.     

Effects of age and sex on pattern electroretinograms and visual evoked potentials

Pattern-electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were simulataneously recorded in 112 normal individuals aged 20–75. Two sized checks subtending 15′ and 31′ were used as stimuli. A weighted regression analysis was used to determine which of the variables, sex or age, was significant. The latency of the a and b wave of the P-ERGs showed a progressive increase with age but no difference between sexes. The effect was statistically significant for both 15′ and 31′ checks. There was no statistically significant aging effects for VEPs elicited by 31′ checks. Aging, however, affected N70, P100, and the interpeak interval between b wave to N70 and b wave to P100 for responses to 15′ checks. Shorter VEP latencies were noted in females for both 15′ and 31′ checks.The simultaneous recording of P-ERGs and VEPs has demonstrated that aging is a major variable at the retinal level. The effects on the a and b waves are mostly due to optic changes with aging and only partially to aging changes in the neuronal retinal circuitry. The effect of aging on VEPs is different for different size stimuli. The cause is a random neuronal cell loss in the visual pathways from the optic nerve to the visual cortex as the individual ages.The difference in VEP data between sexes may be related to anatomical size and hormonal influences.     

Ontogeny of visual acuity in two species of deermice (Peromyscus)

Development of visual acuity in Peromycsus maniculatus and P. leucopus was measured by optokinetic responses. Mice were suspended within a rolating drum lined with black and white stripes of equal width. Stripe width was varied to determine the minimum visual angle which could be seen by each mouse. At 20-cm stimulus distance both species reached a mean visual angle of 21′ of arc by 2 days after eye opening. Development was slower at 40-cm stimulus distace, both species reaching a mean angle of 18′ of arc by 8 days after eye opening. Mean visual angles at three illuminance levels (4·3 lux, 86·1 lux and 861·1 lux) were not diferent. Deermice have better visual acuity and visual range than previously tested rodents and exhibit rapid visual maturation.     

Scalp-recorded oscillatory potentials evoked by transient pattern-reversal visual stimulation in man

Replicable oscillatory potentials, time-locked to pattern stimuli (9.0° central; counterphase reversal at 2.13 Hz) were dissociated from conventional, broad-band VEPs recorded in healthy volunteers at occipital scalp locations by high-pass digital filtering at 17.0–20.0 Hz. Nine consecutive wavelets were identified with a 56.4 ± 8.4 msec mean latency of the first replicable wavelet and mean peak-to-peak amplitude varying between 0.9 and 2.0 μV. The first 2 wavelets had significantly shorter latencies than wave N70 of unfiltered VEP, whereas the last 2 wavelets had longer latencies than N145. Latency and amplitude values varied as a function of contrast and spatial frequency of the stimulus, with shorter latencies and larger amplitudes at 60–90% contrast level and tuning of amplitude at 5.0 c/deg. All wavelets were correlated with wave P100 of unfiltered VEP, while a correlation with N70 of VEP was observed only for those wavelets with latencies in the range of wave P100. Two patients with documented brain lesions involving the visual system are described as examples of oscillatory responses occurring irrespective of filter bandpass and instead of the expected conventional VEP when the generation of these is interfered with by brain pathology. A substantial cortical contribution to the origin of the oscillatory response is conceivable. It is suggested that the oscillatory response to pattern-reversal stimulation reflects events in the visual system that are parallel to, and partly independent of, the conventional VEP, with potential application in research or for clinical purposes.     

Utility of visual evoked potentials using hemifield stimulation and several check sizes in the evaluation of suspected multiple sclerosis

One hundred and eleven patients with suspected multiple sclerosis (64 possible, 47 probable) and 16 with a definite diagnosis of MS were evaluated with pattern-reversal visual evoked potentials (VEPs), employing monocular full-field checks subtending 7′, 14′ and 28′ of visual angle, and right and left hemifield 28′ checks. Thirty-seven patients (29%) had a completely normal study. Sixty-six patients (52%) had abnormal responses to full-field 28′ checks, and in 13 (10%) of these, additional abnormalities were found in one or more of the other test conditions, which indicated the presence of an additional site of dysfunction in the visual pathway. Twenty-four patients (19%) with ‘normal’ full-field 28′ response had abnormalities in one or more of the other test conditions; these included prolonged latency to small size (7′ and 14′) full-field checks, abnormal responses in homonymous hemifields, and abnormal responses limited to a hemifield of one eye. Thus, the use of several check sizes and hemifield stimulation not only increases the sensitivity of VEPs in the evaluation of patients with suspected demyelinating disease, but enhances the capability of the VEP to demonstrate more than one area of visual system impairment.     

Effects of chlorpromazine on pattern and flash ERGs and VEPs compared to oxazepam and to placebo in normal subjects

Antidopaminergic drugs delay the pattern-reversal VEP (P-VEP) and the flash VEP (F-VEP) and, in separate studies, reductions in the amplitude and increases in the latencies of scotopic ERGs have been reported. This study investigated the effects of chlorpromazine (CPZ) on the pattern ERG (P-ERG), P-VEP, flash ERGs and VEPs and oscillatory potentials (OPs). Normal volunteers (N = 15) were administered a placebo, or a single dose of CPZ 100 mg or oxazepam (OZP) 15 mg at weekly intervals, in a double-blind crossover design. A gold foil-ipsilateral ear derivation and an Oz′-Fz derivation were used for the ERG and VEP recordings, respectively. The latencies of ‘mixed’ and cone ERGs were significantly prolonged after CPZ compared to both placebo and to OZP. Amplitudes of rod- and cone-dominated ERGs were reduced following CPZ administration. All components of the OPs were significantly delayed after CPZ administration. No significant intertreatment differences were found in the F-VEP results. The P-ERG P50 peak and the P-VEP N70 and P100 peaks were significantly delayed after CPZ in the case of 28′ checks but not 55′ checks. Retinocortical times and P-ERG and P-VEP amplitudes were not significantly affected. In contrast to CPZ, the administration of OZP had virtually no significant effects compared to placebo. These findings suggest that the antidopaminergic CPZ has a primary effect on retinal electrophysiology. Similar findings have been reported in Parkinson's disease and in animal models.     

Initial findings on visual acuity thresholds in an African elephant (Loxodonta africana)

There are only a few published examinations of elephant visual acuity. All involved Asian elephants (Elephas maximus) and found visual acuity to be between 8′ and 11′ of arc for a stimulus near the tip of the trunk, equivalent to a 0.50 cm gap, at a distance of about 2 m from the eyes. We predicted that African elephants (Loxodonta africana) would have similarly high visual acuity, necessary to facilitate eye‐trunk coordination for feeding, drinking and social interactions. When tested on a discrimination task using Landolt‐C stimuli, one African elephant cow demonstrated a visual acuity of 48′ of arc. This represents the ability to discriminate a gap as small as 2.75 cm in a stimulus 196 cm from the eye. This single‐subject study provides a preliminary estimate of the visual acuity of African elephants. Zoo Biol 29:30–35, 2010. © 2009 Wiley‐Liss, Inc.     

Recovery functions of early cortical median nerve SSEP components: normative data

The recovery functions of parietal P14-N20, N20-P27 and frontal P22-N30 amplitudes were assessed in 17 healthy controls aged 20–50 years by means of the paired stimulus technique. One unpaired and 4 paired stimuli with interstimulus intervals (ISIs) of 25, 50, 75 and 100 msec were cyclically presented in a single run. Responses to the unpaired stimulus were subtracted off-line from paired stimulus responses. The highest suppression was reached at shorter ISIs for components with shorter latencies. The mean suppression of P22-N30 was influenced by the subject's age, being greater in younger subjects. Normative data are reported.     

视觉诱发电位(VEP)方位效应与刺激位置的关系

以人视觉诱发电位(VEP)反应为指标,在视野的不同位置测定了VEP对四个方位的闪烁方波光栅刺激(时间频率2.9Hz,空间频率1.4c/deg,对比度0.94)的反应幅度。在距中央凹20°视角同心圆的八个刺激位置上,VEP反应幅度对与向心线垂直方位的光栅刺激(同心圆的切线方向),有统计意义上的优势。这一规律在垂直、水平向心线上尤为明显。从总体上未发现VEP反应幅度与刺激光栅方位有着明显的关系。这说明在人视野周边区,VEP反应幅度与光栅方位和向心线的夹角(偏向角)相关,而与光栅的绝对方位无关。在相同的刺激条件下,中央区的VEP反应幅度与刺激光栅方位之间也未发现明显关系。     

Light sensitivity of the central and peripheral sections of the retina in exposure to noise

Light sensitivity of the central and peripheral parts of the human retina has been studied in an hour exposure to broadband noise of 95 dBA intensity and in an after-effect period. The indices of time threshold of dark adaptation and the visual acuity restoration time at reduced brightness were analysed. Four types of response to acoustic stimulus have been revealed. Correlation between the initial levels of the indices and the character of changes of the functions studied has been established.     

Trial on the objective evaluation of visual acuity and its maturation by the method of evoked visual potentials]

We have developed a method to estimate foveal visual acuity (VA) through analysis of VEPs. It consists in determining the smallest check size in a pattern reversal that elicits a significant cortical response. The VEP is regarded as significant if the P 100 amplitude reaches a pre-established level in the signal to noise ratio. A valid criterion to determine normal VEP-VA emerges from the testing of 84 emmetropic and ametropic eyes: within our stimulation and recording conditions, a significant VEP response to the reversal of seven minutes checks corresponds to normal foveal acuity. This criterion has also proved pertinent to discriminate between normal VAs of 20/20 and decreased VAs (20/40 or less) with four other groups of subjects: 14 adult eyes whose VAs of 20/20 are decreased through Bangerter occlusives, 32 emmetropic and ametropic eyes belonging to five-years-olds children, 28 emmetropic and ametropic eyes of twelve-years-olds. In order to guarantee the validity of our results we carried out a double-blind study with ophthalmologists. The relevance of the method we suggest is related to that of the method which consists in extrapolating the regression line between VEP amplitudes and the pattern element sizes. At least we have aimed at establishing VEP norms for the maturation of VA. We have collected data from the following subjects: 5 infants tested monthly between 1 and 6 months, 31 infants ranging in age from 1 to 16 months, 10 five-year-old children, 13 twelve-year-olds, and 11 subjects aged 20. Within our stimulation and recording conditions a significant evoked response to the reversal of seven minute checks can be observed from 8 months onward. With an eight-month-old infant this response to the reversal of seven minute checks cannot be identified to the same response with an adult. There are two major differences: the latency of the major positive component is longer, and the structure of the evoked response consists of fewer components.     

Ocular tracking: behavior and neurophysiology.

'Ocular tracking' refers to visually driven, slow eye movements that stabilize moving images on the retina, thereby facilitating high acuity vision. Recent behavioral studies have shown that the primate brain produces several kinds of ocular tracking responses that operate precisely and consistently, with ultra-short latencies. Electrophysiological studies indicate that these tracking responses are mediated by a pathway that includes the medial superior temporal area of the cerebral cortex. Responses of neurons in this pathway are consistent with the short latencies and complex visual properties observed in behavioral studies of the tracking response.     

Lack of the Sodium-Driven Chloride Bicarbonate Exchanger NCBE Impairs Visual Function in the Mouse Retina

Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pH_i) and chloride concentration ([Cl⁻]_i) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABA_A receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pH_i regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function.     

Contrast transfer function of the visual system]

Visually evoked potentials were used to determine the spatial contrast response function of the visual system and the visual acuity of the pigeon. The spatial contrast response describes the relationship between the contrast in a pattern of vertical stripes, whose luminance is a function of position, and the amplitude of the visually evoked response at various spatial frequencies for a given temporal frequency (pattern reversal frequency); it indicates how particular spatial frequencies are attenuated in the visual system. The visually evoked responses were recorded using monopolar stainless steel electrodes inserted into the stratum griseum superficiale of the optic tectum; the depth of penetration was determined on the basis of a stereotactic atlas. The stimulus patterns were generated on a video monitor placed 75 cm in front of the animal's eye perpendicular to the optic axis. The spatial contrast response function measured at 10% contrast and 0.5 Hz reversal frequency shows a peak at a spatial frequency of 0.5 c/deg, corresponding to 1 degree of visual angle, and decreases progressively at higher spatial frequencies. The high-frequency limit (cut-off frequency) for resolution of sinusoidal gratings, estimated from the contrast response function, is 15.5 c/deg, corresponding to a visual acuity of 1.9 min of arc.     

Latency of visually evoked saccadic eye movements

The validness of a model describing the relation between mean saccadic latency and stimulus asynchrony based on facilitation instead of suppression was tested experimentally. As a result, suppression of signals generated by the onset of a peripheral stimulus due to fixation of another target, giving rise to an increase of mean saccadic latency, does not seem very likely. The influence of the intensity of the fixation target on the latency of visually evoked saccades was studied. According to the facilitation model, the offset of the fixation target induces after an afferent delay, a transition of the state of the facilitation mechanism from the unfacilitated condition into a mode of maximal facilitation. The time-period during which this change is accomplished is called Facilitation-Rise-Time (FRT). An interpretation within the context of the facilitation model of gap-overlap latency data for different values of the intensity of the fixation stimulus suggests, in combination with computer-computations of the model, that lowering of this intensity causes an increase in FRT. The results in normal subjects of step stimulus experiments with a dim fixation point substantiate the hypothesis of a facilitation mechanism, which is triggerable not only by an external signal such as the offset of the fixation point, but also by some internal stimulus independent signal. Moreover, data for tracking by an amblyopic eye seem to support this conclusion. The findings of increased saccadic latencies in amblyopic and Optic Neuritis (ON) eyes suggest a slowing of processing of visual information in the sensory pathways from the central retina, subsequently utilized by the oculomotor system in the generation of saccades.(ABSTRACT TRUNCATED AT 250 WORDS)     

VisioTracker,an Innovative Automated Approach to Oculomotor Analysis

Investigations into the visual system development and function necessitate quantifiable behavioral models of visual performance that are easy to elicit, robust, and simple to manipulate. A suitable model has been found in the optokinetic response (OKR), a reflexive behavior present in all vertebrates due to its high selection value. The OKR involves slow stimulus-following movements of eyes alternated with rapid resetting saccades. The measurement of this behavior is easily carried out in zebrafish larvae, due to its early and stable onset (fully developed after 96 hours post fertilization (hpf)), and benefitting from the thorough knowledge about zebrafish genetics, for decades one of the favored model organisms in this field. Meanwhile the analysis of similar mechanisms in adult fish has gained importance, particularly for pharmacological and toxicological applications.Here we describe VisioTracker, a fully automated, high-throughput system for quantitative analysis of visual performance. The system is based on research carried out in the group of Prof. Stephan Neuhauss and was re-designed by TSE Systems. It consists of an immobilizing device for small fish monitored by a high-quality video camera equipped with a high-resolution zoom lens. The fish container is surrounded by a drum screen, upon which computer-generated stimulus patterns can be projected. Eye movements are recorded and automatically analyzed by the VisioTracker software package in real time.Data analysis enables immediate recognition of parameters such as slow and fast phase duration, movement cycle frequency, slow-phase gain, visual acuity, and contrast sensitivity.Typical results allow for example the rapid identification of visual system mutants that show no apparent alteration in wild type morphology, or the determination of quantitative effects of pharmacological or toxic and mutagenic agents on visual system performance. Download video file.^{(36M, mov)}     

Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis

Background

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON.

Methods

Medical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse.

Results

All MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO.

Conclusions

NMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.

     

Can video images imitate real stimuli in animal behaviour experiments?

The use of video images in place of natural stimuli in animal behaviour experiments is reviewed. Unlike most other artificial means of stimulus presentation, video stimuli can depict complex moving objects such as other animals, preserving the temporal and spatial patterns of movement precisely as well as colour and sounds for repeated playback. Computer editing can give flexibility and control over all elements of the stimulus. A variety of limitations of video image presentation are also considered. Televisions and video monitors are designed with human vision in mind, and some non-human animals that differ in aspects of visual processing such as their colour vision, critical flicker-fusion threshold, perception of depth and visual acuity, may perceive video images differently to ourselves. The failure of video stimuli to interact with subjects can be a drawback for some studies. For video to be useful, it is important to confirm that the subject animal responds to the image in a comparable way to the real stimulus, and the criteria used to assess this are discussed. Finally, the contribution made by video studies to date in the understanding of animal visual responses is considered, and recommendations as to the future uses of video are made.