Temporal Integration in Visual Cortex of Cats with Surgically Induced Strabismus

Single unit response latencies in striate cortex after visual stimulation with stationary flashed bars were measured and interocularly compared in anaesthetized cats with surgically induced strabismus, in order to elucidate the neural basis of strabismic amblyopia. Four unilateral esotropic and two exotropic cats were studied. The visual onset latencies of cortical neurons ranged from 30 to 170 ms after stimulation of the non-deviating eye at a contrast of 82%. Responses after visual stimulation of the deviating eye were consistently delayed by ∼10 ms. The latency increase was independent of the direction and absolute angle of squint in the different animals. Peak latencies of cortical neurons ranged from 43 to 245 ms. Median peak latency was 85 ms for the non-deviating and 95 ms for the deviating eye. The rise time of cortical flash responses, as determined from onset - peak differences, ranged between 2 and 170 ms. Direct interocular comparison of response latencies in the remaining binocular neurons revealed an invariable advantage for the non-deviating eye. Supragranular neurons showed a greater interocular latency difference than neurons in layer IV. Visual latencies were contrast-dependent. However, the latency reduction with increasing contrast was less pronounced for the deviating eye. We discuss the possibility that central integration times, especially within cortex, are prolonged in strabismic cats, affecting temporal coincidence of signal processing in the visual cortex. The resulting disturbance of spatio-temporal integration, as caused by a scrambling of geniculo-striate and intracortical connections, may be the substrate of binocular suppression and strabismic amblyopia.     

Squint Affects Synchronization of Oscillatory Responses in Cat Visual Cortex

As shown previously, neurons in various areas of the cat's visual cortex respond to appropriate visual stimuli with oscillatory activity in the frequency range of 30 – 70 Hz. It has been suggested that synchronization of such responses serves to define assemblies of coherently active cells which represent individual visual objects. In this study, we have investigated this putative binding mechanism in the visual cortex of strabismic cats. We used six adult cats in which divergent squint had been induced surgically at the age of 3 weeks. Multiunit activity was recorded from area 17 with arrays of four or five closely spaced microelectrodes. Subsequently, auto- and cross-correlation functions were computed for all spike trains. To quantify the oscillatory nature of the responses and the strength of synchronization between spatially remote sites, damped sine wave functions were fitted to the correlograms. Analysis of responses obtained from 202 recording sites showed that the vast majority of cells had become monocular. Auto-correlation analysis revealed that the proportion of oscillatory firing patterns was similar to that observed in normal cats. However, cross-correlation analysis of 153 response pairs demonstrated that synchronization was reduced significantly between cells dominated by different eyes while it was as frequent and strong as in normal cats between cells dominated by the same eye. These findings indicate that strabismus not only causes a reorganization of afferent inputs but also affects intracortical interactions. Since strabismic cats lack tangential intracortical connections between territories connected to different eyes and are unable to combine signals conveyed by the two eyes these results support the notion that response synchronization is achieved by cortico-cortical connections and serves as a mechanism for feature binding.     

Ocular dominance, eye alignment and visual acuity in kittens reared with an optically induced squint

A horizontal concomitant strabismus produced optically in kittens with prisms caused a decrease in the proportion of binocularly excitable striate neurons with approximately equal percentages of neurons being driven by each eye. In addition, preventing fusion with prisms resulted in alterations in interocular alignment and in some cases a mild strabismic amblyopia. The changes in ocular dominance were dependent on the amount and direction of the prism induced deviation; however, regardless of the type of prisms worn, the kittens which demonstrated interocular misalignments were esotropic.     

Selectivity as well as sensitivity loss characterizes the cortical spatial frequency deficit in amblyopia

The processing deficit in amblyopia is not restricted to just high spatial frequencies but also involves low‐medium spatial frequency processing, for suprathreshold stimuli with a broad orientational bandwidth. This is the case in all three forms of amblyopia; strabismic, anisometropic, and deprivation. Here we use both a random block design and a phase‐encoded design to ascertain (1) the extent to which fMRI activation is reduced at low‐mid spatial frequencies in different visual areas, (2) how accurately spatial frequency is mapped across the amblyopic cortex. We report a loss of function to suprathreshold low‐medium spatial frequency stimuli that involves more than just area V1, suggesting a diffuse loss in spatial frequency processing in a number of different cortical areas. An analysis of the fidelity of the spatial frequency cortical map reveals that many voxels lose their spatial frequency preference when driven by the amblyopic eye, suggesting a broader tuning for spatial frequency for neurons driven by the amblyopic eye within this low‐mid spatial frequency range. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Voxel-based analysis of MRI detects abnormal visual cortex in children and adults with amblyopia

Amblyopia, sometimes called "lazy eye," is a relatively common developmental visual disorder well characterized behaviorally; however, the neural substrates associated with amblyopia in humans remain unclear. We hypothesized that abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly as a result of experience-dependent neuronal plasticity. Anatomic magnetic resonance imaging (MRI) and psychophysical vision testing was carried out on 74 subjects divided into two age ranges, 7-12 years and 18-35 years, and three diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We report a behavioral impairment in contrast sensitivity for subjects with amblyopia, consistent with previous reports. When the high-resolution MRI brain images were analyzed quantitatively with optimized voxel-based morphometry, results indicated that adults and children with amblyopia have decreased gray matter volume in visual cortical regions, including the calcarine sulcus, known to contain primary visual cortex. This finding was confirmed with a separate region-of-interest analysis. For the children with amblyopia, additional gray matter reductions in parietal-occipital areas and ventral temporal cortex were detected, consistent with recent reports that amblyopia can result in spatial location and object processing deficits. These data are the first to provide possible neuroanatomic bases for the loss of binocularity and visual sensitivity in children and adults with amblyopia.     

Stimulus-dependent oscillations in the cat visual cortex: differences between bar and grating stimuli

We have investigated the dependence of cortical oscillations on the type of visual stimulus. Single unit recordings were performed in areas 17 and 18 of the cat visual cortex. Among 217 cortical neurons oscillations in the frequency range of 22–102 Hz were found in 29 cells (13%). The proportion of oscillating cells was higher (16%) if both bar and grating stimuli were used to stimulate cortical neurons. It was found that gratings are more effective than bars in triggering oscillatory patterns in cortical cells. Among 21 oscillating cells which were stimulated with both bar and grating stimuli, oscillations evoked with gratings were found in 17 neurons (81%) while oscillations evoked with bar stimuli were triggered in 7 cells (33%). The distributions of oscillation frequencies were statistically different for oscillations evoked with bars and gratings. Frequencies of oscillations evoked with bars were in the lower and higher range than frequencies of oscillations evoked with gratings. In 3 cells (14%), rhythmic patterns could be evoked with both bar and grating stimuli. However, the oscillations were of different frequencies. No significant correlation was found between the strength of oscillations and firing rate of cortical neurons. Both simple and complex cells manifested the same dependence on stimulus type. However, complex cells mostly exhibited oscillations in the lower frequency range while simple cells did so when neurons were stimulated with bars. The results suggest that various classes of visual stimuli can be coded by a temporal pattern of cortical responses.     

Interocular Suppression in Primary Visual Cortex in Strabismus

People with strabismus acquired during childhood do not experience diplopia (double vision). To investigate how perception of the duplicate image is suppressed, we raised two male monkeys with alternating exotropia by disinserting the medial rectus muscle in each eye at age four weeks. Once the animals were mature, they were brought to the laboratory and trained to fixate a small spot while recordings were made in primary visual cortex (V1). Drifting gratings were presented to the receptive fields of 500 single neurons for eight interleaved conditions: (1) right eye monocular; (2) left eye monocular; (3) right eye''s field, right eye fixating; (4) right eye''s field, left eye fixating; (5) left eye''s field, right eye fixating; (6) left eye''s field, left eye fixating; (7) both eyes'' fields, right eye fixating; (8) both eyes'' fields, left eye fixating. As expected, ocular dominance histograms showed a monocular bias compared with normal animals, but many cells could still be driven via both eyes. Overall, neuronal responses were not affected by switches in ocular fixation. Individual neurons exhibited binocular interactions, but mean population indices indicated no net interocular suppression or facilitation. Even neurons located in cortex with reduced cytochrome oxidase (CO) activity, representing portions of the nasal visual field where perception is suppressed during binocular viewing, showed no net inhibition. These data indicate that V1 neurons do not appear to reflect strabismic suppression and therefore the elimination of diplopia is likely to be mediated at a higher cortical level.SIGNIFICANCE STATEMENT In patients with strabismus, images fall on non-corresponding points in the two retinas. Only one image is perceived, because signals emanating from the other eye that convey the duplicate image are suppressed. The benefit is that diplopia is prevented, but the penalty is that the visual feedback required to adjust eye muscle tone to realign the globes is eliminated. Here, we report the first electrophysiological recordings from the primary visual cortex (V1) in awake monkeys raised with strabismus. The experiments were designed to reveal how perception of double images is avoided.     

A switch from inter‐ocular to inter‐hemispheric suppression following monocular deprivation in the rat visual cortex

Binocularity is a key property of primary visual cortex (V1) neurons that is widely used to study synaptic integration in the brain and plastic mechanisms following an altered visual experience. However, it is not clear how the inputs from the two eyes converge onto binocular neurons, and how their interaction is modified by an unbalanced visual drive. Here, using visual evoked potentials recorded in the juvenile rat V1, we report evidence for a suppressive mechanism by which contralateral eye activity inhibits responses from the ipsilateral eye. Accordingly, we found a lack of additivity of the responses evoked independently by the two eyes in the V1, and acute silencing of the contralateral eye resulted in the enhancement of ipsilateral eye responses in cortical neurons. We reverted the relative cortical strength of the two eyes by suturing the contralateral eye shut [monocular deprivation (MD)]. After 7 days of MD, there was a loss of interocular suppression mediated by the contralateral, deprived eye, and weak inputs from the closed eye were functionally inhibited by interhemispheric callosal pathways. We conclude that interocular suppressive mechanisms play a crucial role in shaping normal binocularity in visual cortical neurons, and a switch from interocular to interhemispheric suppression represents a key step in the ocular dominance changes induced by MD. These data have important implications for a deeper understanding of the key mechanisms that underlie activity‐dependent rearrangements of cortical circuits following alteration of sensory experience.     

Involvement of GABA at the levels of mesencephalic central gray and medial hypothalamus in the elicitation of escape

Visual acuity and visuo-motor behavior were assessed in various models of experimental amblyopia in cats (n = 15). Three models of strabismic amblyopia were studied: surgical esotropia by sectioning one lateral rectus muscle; comitant optical strabismus by rearing cats with goggles which placed a stationary wedge prism before one eye; and incomitant optical strabismus by rearing cats with goggles which placed a rotatable wedge prism before one eye. These cats were compared with normal and monocularly deprived cats.Clear amblyopic deficits were found in monocularly deprived, esotropic and rotating prism cats. The amblyopic deficits were graded among these preparations, being most severe in monocularly deprived cats and least severe in esotropic cats. The degree of behavioral amblyopia in these preparations was correlated with the extent of physiological abnormalities in visual cortex and the lateral geniculate nucleus. Fixed optical strabismus did not result in behavioral deficits and does not appear to be a good model of strabismic amblyopia. Variable optical strabismus, on the other hand, produced clear deficits in one eye, both behaviorally and physiologically, without impaired ocular motility.     

Visual acuity in esotropic cats following occlusion of the non-deviating eye

The present study examined the possibility that strabismic amblyopia may be explained in terms of binocular competition. This was done by measuring visual acuity in strabismic kittens whose deviating eye was placed at an advantage over the other. Four groups of kittens were studied: Normal/Normal (N/N); Lid-sutured/Normal (LS/N); Strabismic/Normal (S/N); Strabismic/Lid-sutured (S/LS). In conditions 2-4 kittens underwent lateral rectus section and/or unilateral lid suture around the time of natural eye opening. Visual acuity measurements were made using the jumping stand technique and the following results were obtained: all S/N kittens showed an acuity deficit in the strabismic eye; each S/LS kitten had a better acuity in the deviating eye than any S/N kitten; the acuity of the LS/S kittens was slightly below that of the N/N kittens or the normal eye of the LS/N kittens. These data suggest that binocular competition can account for essentially all of the strabismic amblyopia observed in kittens.     

Drifting grating stimulation reveals particular activation properties of visual neurons in the caudate nucleus

The role of the caudate nucleus (CN) in motor control has been widely studied. Less attention has been paid to the dynamics of visual feedback in motor actions, which is a relevant function of the basal ganglia during the control of eye and body movements. We therefore set out to analyse the visual information processing of neurons in the feline CN. Extracellular single-unit recordings were performed in the CN, where the neuronal responses to drifting gratings of various spatial and temporal frequencies were recorded. The responses of the CN neurons were modulated by the temporal frequency of the grating. The CN units responded optimally to gratings of low spatial frequencies and exhibited low spatial resolution and fine spatial frequency tuning. By contrast, the CN neurons preferred high temporal frequencies, and exhibited high temporal resolution and fine temporal frequency tuning. The spatial and temporal visual properties of the CN neurons enable them to act as spatiotemporal filters. These properties are similar to those observed in certain feline extrageniculate visual structures, i.e. in the superior colliculus, the suprageniculate nucleus and the anterior ectosylvian cortex, but differ strongly from those of the primary visual cortex and the lateral geniculate nucleus. Accordingly, our results suggest a functional relationship of the CN to the extrageniculate tecto-thalamo-cortical system. This system of the mammalian brain may be involved in motion detection, especially in velocity analysis of moving objects, facilitating the detection of changes during the animal's movement.     

Haphazard neural connections underlie the visual deficits of cats with strabismic or deprivation amblyopia

Identification of the neural basis of the visual deficits experienced by humans with amblyopia, particularly when associated with strabismus (strabismic amblyopia), has proved to be difficult in part because of the inability to observe directly the neural changes at various levels of the human visual pathway. Much of our knowledge has necessarily been obtained on the basis of sophisticated psychophysical studies as well as from electrophysiological explorations on the visual pathways in animal models of amblyopia. This study combines these two approaches to the problem by employing similar psychophysical probes of performance on animal models of two forms of amblyopia (deprivation and strabismic) to those employed earlier on human amblyopes (Hess & Field, 1994, Vis. Res., 34, 13397-13406). The tests explore two competing explanations for the visual deficits, namely an evenly distributed loss of neural connections (undersampling) with the amblyopic eye as opposed to disordered connections with this eye (neural disarray). Unexpectedly, the results in animal models of deprivation amblyopia were not in accord with expectations based upon an even distribution of lost connections with the amblyopic eye. However, the results were similar to those observed in a strabismic amblyopic animal and to strabismic amblyopic humans. We suggest that deprivation amblyopia may be accompanied by an uneven loss of connections that results in effective neural disarray. By contrast, amblyopia associated with strabismus might arise from neural disarray of a different origin such as an alteration of intrinsic cortical connections.     

Spatial Resolution and Contrast Sensitivity of Single Neurons in Area 19 of Split-chiasm Cats: A Comparison With Primary Visual Cortex

Electrophysiological recordings were carried out in the callosal recipient zone of area 19 in normal and split-chiasm cats and, for comparison purposes, at the border of areas 17 and 18 of split-chiasm cats. The influences of retinothalamic and callosal inputs on a single cortical neurons were thereby evaluated. Extracellular recordings of single cells were made in anaesthetized and paralysed cats in the zone representing the central visual field. Receptive field properties were assessed using sine wave gratings drifting in optimal directions. Results showed that in area 19 and areas 17/18 one-third of the cells were binocularly driven after section of the optic chiasm. In area 19, the spatial resolution and contrast sensitivity of cells driven via the dominant eye were similar in the normal and split-chiasm groups. In areas 17/18 and area 19 of split-chiasm cats, binocular cells showed significant interocular matching of their receptive field properties (spatial resolution and contrast threshold), although small differences were observed. These small interocular differences were related to the cell's Ocular dominance rather than to the signal transmission route (thalamic or callosal).     

Non-dominant eye responses in the dorsal lateral geniculate nucleus of the cat: an intracellular study

While binocularity has been established as an important characteristic of cat visual cortical neurons, neurons in the dorsal lateral geniculate nucleus (LGNd) are commonly believed to be monocular. To test whether binocularity exists at the level of the LGNd, postsynaptic potentials (PSPs) of 101 cells were intracellularly recorded in eight normal and eight monocularly deprived cats while presenting stimuli to either the dominant or non-dominant eyes. The results showed that: (1) About 92% of neurons (45 out of 49) responded to a flashing spot presented to the non-dominant eye. In contrast to the dominant eye responses, the non-dominant eye PSPs usually exhibited the same polarization tendency (hyperpolarization or depolarization) to flashing spot stimuli of light increment or decrement, and most of them were inhibitory (hyperpolarization, 35 out of 45, 78%). (2) The response field (RF) of the non-dominant eye overlapped that of the dominant eye. (3) For most binocular cells, peak-to-peak amplitudes of non-dominant eye PSPs were about half the size (46%) of those of the dominant eye. The peak latencies and half-peak latencies of non-dominant eye PSPs were significantly longer than those of the dominant eye (mean differences were 5.4 ms and 5.6 ms respectively). (4) Most of the binocular cells responded well to contrast reversing gratings presented to the non-dominant eye, and the responses were clearly spatial-frequency tuned. No null phase could be found for non-dominant eye PSPs, no matter the neuron was classified as X or Y type according to dominant eye elicited responses. Some of the cells responded well to drifting gratings presented to the non-dominant eye. (5) We also recorded 52 cells in monocularly deprived cats, and found that 49 cells (94%) showed significant responses to flashing spots presented to the non-dominant eye, a similar percentage to that found in normal cats (92%). CONCLUSION: as strongly monocular neurons, most of LGNd cells could also be driven by the non-dominant eye. The responses evoked by non-dominant eye stimulation differ greatly from those evoked by dominant eye stimulation, and remain intact even without visual experience. These observations suggest an important role of the perigeniculate nucleus in providing binocular inputs to LGNd cells.     

Effects of early unilateral blur on the macaque's visual system. III. Physiological observations

We studied the properties of visual cortical and lateral geniculate neurons in 5 macaque monkeys raised with the vision of one eye blurred by daily instillation of atropine. This rearing reduced the degree of binocular interaction in striate cortical neurons and caused a modest shift in eye dominance away from the atropine-treated eye. It also led to a difference in the spatial properties of neurons driven by the 2 eyes: neurons driven by the treated eye tended to have lower optimal spatial frequencies, poorer spatial resolution, and lower contrast sensitivity than neurons driven by the untreated eye. Some of the few binocularly driven neurons had receptive fields with sharply different spatial properties in the 2 eyes, with the treated eye's receptive field always having poorer spatial resolution. In striate cortex, the effects on neuronal spatial properties were less marked in layer 4 than in more superficial or deeper layers; there was no difference in the spatial properties of lateral geniculate neurons driven by the 2 eyes. A small sample of extrastriate cortical neurons from a single animal showed effects similar to those seen in striate cortex. The striate cortical changes varied consistently from animal to animal: The less affected animals had no discernible eye dominance shift and relatively small differences in spatial properties between the eyes; the more affected animals had substantial eye dominance shifts and larger interocular spatial differences. These variations were also reflected in, and consistent with, behavioral and anatomical measurements performed in the same monkeys.     

Spatial consistency of neural firing regulates long-range local field potential synchronization: A computational study

Local field potentials (LFPs) are thought to integrate neuronal processes within the range of a few millimeters of radius, which corresponds to the scale of multiple columns. In this study, the model of LFP in the visual cortex proposed by Mazzoni et al. (2008) was adapted to organize a network of two cortical areas, in which pyramidal neurons were divided into two sub-population modeling columns with spatially organized connections to neurons in other areas. Using the model enabled the relationship between neural firing and LFP to be evaluated, in addition to the LFP coherence between the two areas. Results showed that: (1) neurons in a particular sub-population generated the LFP in the area; (2) the spatial consistency of neural firing in the two areas was strongly correlated with LFP coherence; and (3) this consistency was capable of regulating LFP coherence in a lower frequency band, which was originally introduced to neurons in a particular sub-population. These results were derived from a winner-take-all operation in the columnar structure; thus, they are expected to be common in the cortex. It is suggested that the spatial consistency of neural firing is essential for regulating long-range LFP synchronization, which would facilitate neuronal integration processes over multiple cortical areas.     

Binocularly deprived cats: binocular tests of cortical cells show regular patterns of interaction

If an animal is prevented from receiving visual experience during an early developmental phase, pronounced dysfunctions are observed. Physiological tests reveal gross abnormalities in the striate cortex. Cells in visual cortex are either unresponsive of their response characteristics are erratic. Although fewer than normal numbers of binocular cells are found in cats reared with binocular lid suture, a population remains that can be activated by stimulation through either eye. We have studied cortical cells in binocularly deprived cats in order to specify monocular and binocular response characteristics. The primary hypothesis we have examined is that the abnormal response properties of these cells are a result of an irregular structure or substructure of the receptive fields. Kittens were binocularly lid-sutured soon after birth, and were studied physiologically at ages between 7 and 11 months. Standard techniques were used to record from single cells in striate cortex. Drifting gratings were presented to either eye or to both eyes together. In the latter case, the relative interocular phase was varied between the gratings so that the retinal disparity of the stimuli was changed. We confirmed the expected finding that most cells were either unresponsive or erratic in their response. Of the cells that responded, monocular tuning functions for orientation and spatial frequency of the stimulus were often irregular. However, even in these cases, binocular interaction patterns of cortical responses were nearly always highly regular and displayed phase-specific profiles. A model is presented that explains this finding and suggests how binocular deprivation may result in disorganized receptive-field structure.     

Nonlinear Spatial Integration Underlies the Diversity of Retinal Ganglion Cell Responses to Natural Images

How neurons encode natural stimuli is a fundamental question for sensory neuroscience. In the early visual system, standard encoding models assume that neurons linearly filter incoming stimuli through their receptive fields, but artificial stimuli, such as contrast-reversing gratings, often reveal nonlinear spatial processing. We investigated to what extent such nonlinear processing is relevant for the encoding of natural images in retinal ganglion cells in mice of either sex. We found that standard linear receptive field models yielded good predictions of responses to flashed natural images for a subset of cells but failed to capture the spiking activity for many others. Cells with poor model performance displayed pronounced sensitivity to fine spatial contrast and local signal rectification as the dominant nonlinearity. By contrast, sensitivity to high-frequency contrast-reversing gratings, a classical test for nonlinear spatial integration, was not a good predictor of model performance and thus did not capture the variability of nonlinear spatial integration under natural images. In addition, we also observed a class of nonlinear ganglion cells with inverse tuning for spatial contrast, responding more strongly to spatially homogeneous than to spatially structured stimuli. These findings highlight the diversity of receptive field nonlinearities as a crucial component for understanding early sensory encoding in the context of natural stimuli.SIGNIFICANCE STATEMENT Experiments with artificial visual stimuli have revealed that many types of retinal ganglion cells pool spatial input signals nonlinearly. However, it is still unclear how relevant this nonlinear spatial integration is when the input signals are natural images. Here we analyze retinal responses to natural scenes in large populations of mouse ganglion cells. We show that nonlinear spatial integration strongly influences responses to natural images for some ganglion cells, but not for others. Cells with nonlinear spatial integration were sensitive to spatial structure inside their receptive fields, and a small group of cells displayed a surprising sensitivity to spatially homogeneous stimuli. Traditional analyses with contrast-reversing gratings did not predict this variability of nonlinear spatial integration under natural images.     

The spatial tuning of steady state pattern electroretinogram in multipie sclerosis

In normal subjects, the steady-state electroretinogram in response to contrast reversing gratings (PERG), is spatially band-pass tuned in amplitude, with a maximum at intermediate spatial frequencies and an attenuation at lower and higher ones. The amplitude attenuation at low spatial frequencies is believed to reflect centre-surround antagonistic interactions in the receptive fields of inner retinal neurons. The aim of this study was to evaluate the PERG spatial tuning in multiple sclerosis (MS) patients without a previous optic neuritis history. Steady- state PERGs in response to counterphase-modulated (8 Hz) sinusoidal gratings of variable spatial frequency (0.6, 1.0, 1.4, 2.2 and 4.8 c/deg), were recorded from 18 patients with definite or probable MS and no history of optic neuritis (ON-). Nine of them had no signs of subclinical optic nerve demyelination (asymptomatic) in either eye, while nine had symptoms or signs of optic pathways involvement (symptomatic) in one or both eyes. Results were compared with those obtained from 10 MS patients with a previous history of optic neuritis (ON+) in one or both eyes, as well as from 21 age-matched controls. The amplitudes and phases of the responses' 2nd harmonics were measured. Compared with the controls, asymptomatic ON- patients showed selective losses in mean PERG amplitudes at medium and high (1.0-4.8 c/deg) spatial frequencies. Symptomatic ON- patients and ON+ patients had reductions in mean PERG amplitudes, with respect to controls, involving the whole spatial frequency range, but with greater losses at medium-high (1.0-4.8 c/deg) than at lower spatial frequencies. In all patients' groups, the average PERG spatial tuning function differed significantly from that of the controls, assuming a low-pass instead of the normal band-pass shape. The PERG phase was delayed in ON+ but not in ON- patients, as compared to controls. However, the phase delay was independent of spatial frequency. In both ON- and ON+ patients, losses in PERG amplitude and spatial tuning tended to be associated with corresponding abnormalities in perimetric sensitivity, visual acuity, colour vision and transient visual evoked potential (VEP) latency. The results indicate that abnormalities of the spatial tuning of steady-state PERG can be found in MS patients without either optic neuritis or signs of subclinical optic nerve demyelination. These changes may reflect a retinal dysfunction, developing early in the course of MS, due to a loss of specific subpopulations of inner neurons, changes in lateral interactions of their receptive fields, or both.     

High-frequency oscillations (20 to 120 Hz) and their role in visual processing.

Oscillatory firing of neurons in response to visual stimuli has been observed to occur with different frequencies at multiple levels of the visual system. In the cat retina, oscillatory firing patterns occur with frequencies in the range of 60 to 120 Hz (omega-oscillations). These millisecond-precise temporal patterns are transmitted reliably to the cortex and may provide a feed-forward mechanism of response synchronization. In the cortex, visual responses often show oscillatory patterning with frequencies between 20 and 60 Hz (gamma-oscillations), which are not phase locked to the stimulus onset and therefore do not show up in regularly averaged evoked potentials. Gamma-oscillatory responses synchronize with millisecond precision over long distances and are mediated by the reciprocal corticocortical connectivity. Modulatory systems like the ascending reticular activating system facilitate synchronization and increase the strength of gamma-oscillations. During states of such functional cortical activation, the dominant frequency of the EEG is shifted from lower frequencies in the delta-/theta-range to higher frequencies in the gamma-range. Therefore, functional states indicate different degrees of temporal precision with which large neuronal populations interact. Response synchronization also depends on relations of global stimulus features. This suggests that millisecond-precise neuronal interactions serve as a fundamental mechanism for visual information processing.