Monocular Visual Stimulation Research Articles

White matter and latency of visual evoked potentials during maturation: A miniature pig model of adolescent development

BackgroundContinuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period. MethodsEight Sinclair™ minipigs (Sus scrofa domestica) were evaluated four times during weeks 14–28 (40, 28 and 28 days apart) of adolescence using monocular visual stimulation (1 Hz)-evoked potentials and diffusion MRI (dMRI) of WM. The latency for the pre-positive 30 ms (PP30), positive 30 ms (P30) and negative 50 ms (N50) components of the flash visual evoked potentials (fVEPs) and their interhemispheric latency (IL) were recorded in the frontal, central and occipital areas during ten 60-second stimulations for each eye. The dMRI imaging protocol consisted of fifteen b-shells (b = 0–3500 s/mm2) with 32 directions/shell, providing measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axonal water fraction (AWF), and the permeability-diffusivity index (PDI). ResultsSignificant reductions (p < 0.05) in the latency and IL of fVEP measurements paralleled significant rises in FA, KA, AWF and PDI over the same period. The longitudinal latency changes in fVEPs were primarily associated with whole-brain changes in diffusion parameters, while fVEP IL changes were related to maturation of the corpus callosum. ConclusionsGood agreement between reduction in the latency of fVEPs and maturation of cerebral WM was interpreted as evidence for ongoing myelination and confirmation of the minipig as a viable research platform. Adolescent development in minipigs can be studied using human neuroimaging and neurophysiological protocols and followed up with more invasive assays to investigate key neurodevelopmental hypotheses in psychiatry.

Temporal synchrony discrimination is abnormal in dichoptic but not monocular visual processing in treated anisometropic amblyopes.

To evaluate whether temporal synchrony processing deficits remain when normal visual acuity is restored in adults with unilateral anisometropic amblyopia. We recruited 14 clinically treated anisometropic amblyopes (mean age 23.17 ± 2.53 years) with best-corrected visual acuity ≤ 0.1 logMAR and 15 age-matched emmetropes (mean age 24.40 ± 1.92 years) with normal vision to participate in our experiment. We presented two pairs of flicking Gaussian dots (1Hz) as visual stimuli: one pair of dots was synchronous (reference), and the other pair of dots was asynchronous (signal). Subjects were asked to determine the position of the asynchronous pair. We applied the constant stimuli method to measure the temporal synchrony threshold under monocular and dichoptic viewing conditions. There were eight temporal phase lags in the asynchronous pair. The minimum degree of the temporal phase at which a participant can discriminate a signal pair is defined as the temporal synchrony threshold. Under monocular viewing conditions where both the reference and signal pairs were presented to one eye, the temporal synchrony thresholds of previous amblyopic eyes and fellow eyes were not significantly different (p= 0.15). Under dichoptic viewing conditions where both the reference and signal pairs were dichoptically presented to both eyes, the temporal synchrony threshold in the treated anisometropic amblyopes was significantly higher than that of the controls (119.34 ± 20.43 vs. 99.78 ± 16.60 ms, p= 0.009). There was no significant correlation between the monocular and dichoptic viewing conditions in the treated amblyopes (r= -0.22, p= 0.94). Temporal synchrony discrimination is abnormal under dichoptic but not under monocular visual stimulation in treated anisometropic amblyopes with normalised visual acuity.

GABAergic inhibition in the human visual cortex relates to eye dominance

Binocular vision is created by fusing the separate inputs arriving from the left and right eyes. ‘Eye dominance’ provides a measure of the perceptual dominance of one eye over the other. Theoretical models suggest that eye dominance is related to reciprocal inhibition between monocular units in the primary visual cortex, the first location where the binocular input is combined. As the specific inhibitory interactions in the binocular visual system critically depend on the presence of visual input, we sought to test the role of inhibition by measuring the inhibitory neurotransmitter GABA during monocular visual stimulation of the dominant and the non-dominant eye. GABA levels were measured in a single volume of interest in the early visual cortex, including V1 from both hemispheres, using a combined functional magnetic resonance imaging and magnetic resonance spectroscopy (combined fMRI-MRS) sequence on a 7-Tesla MRI scanner. Individuals with stronger eye dominance had a greater difference in GABAergic inhibition between the eyes. This relationship was present only when the visual system was actively processing sensory input and was not present at rest. We provide the first evidence that imbalances in GABA levels during ongoing sensory processing are related to eye dominance in the human visual cortex. Our finding supports the view that intracortical inhibition underlies normal eye dominance.

Modulation of binocular rivalry with rapid monocular visual stimulation.

Rapid visual stimulation can increase synaptic efficacy by repeated synaptic activation. This long-term potentiation-like (LTP-like) effect can induce increased excitability in the human visual cortex. To examine the effect of rapid visual stimulation on perception, we tested the hypothesis that rapid monocular visual stimulation would increase the dominance of the stimulated eye in a binocular rivalry task. Participants (n=25) viewed orthogonal 0.5cpd gratings presented in a dichoptic anaglyph to induce binocular rivalry. Rivalry dynamics (alternation rate, dominance, and piecemeal durations) were recorded before and after 2min of rapid monocular stimulation (9Hz flicker of one grating) or a binocular control condition (9Hz alternation of the orthogonal gratings viewed binocularly). Rapid monocular stimulation did not affect alternation rates or piecemeal percept duration. Unexpectedly, the rivalry dominance of the stimulated eye was significantly reduced. A further experiment revealed that this effect could not be explained by monocular adaptation. Together, the results suggest that rapid monocular stimulation boosts dominance in the non-stimulated eye, possibly by activating homeostatic interocular gain control mechanisms.

Functional labeling of neurons and their projections using the synthetic activity–dependent promoter E-SARE

Identifying the neuronal ensembles that respond to specific stimuli and mapping their projection patterns in living animals are fundamental challenges in neuroscience. To this end, we engineered a synthetic promoter, the enhanced synaptic activity-responsive element (E-SARE), that drives neuronal activity-dependent gene expression more potently than other existing immediate-early gene promoters. Expression of a drug-inducible Cre recombinase downstream of E-SARE enabled imaging of neuronal populations that respond to monocular visual stimulation and tracking of their long-distance thalamocortical projections in living mice. Targeted cell-attached recordings and calcium imaging of neurons in sensory cortices revealed that E-SARE reporter expression correlates with sensory-evoked neuronal activity at the single-cell level and is highly specific to the type of stimuli presented to the animals. This activity-dependent promoter can expand the repertoire of genetic approaches for high-resolution anatomical and functional analysis of neural circuits.

Accurate decoding of sub-TR timing differences in stimulations of sub-voxel regions from multi-voxel response patterns

We investigated the decoding of ocular dominance stimulations with millisecond-order timing difference from the blood oxygen level dependent (BOLD) signal in human functional magnetic resonance imaging (fMRI). In our experiment, ocular dominance columns were activated by monocular visual stimulation with 500- or 100- ms onset differences. We observed that the event-related hemodynamic response (HDR) in the human visual cortex was sensitive to the subtle onset difference. The HDR shapes were related to the stimulus timings in various manners: the timing difference was represented in either the amplitude of positive peak, amplitude of negative peak, delay of peak time, or response duration of HDR. These complex relationships were different across voxels and subjects. To find an informative feature of HDR for discriminating the subtle timing difference of ocular dominance stimulations, we examined various characteristics of HDR including response amplitude, time to peak, full width at half-maximum response, as inputs for decoding analysis. Using a canonical HDR function for estimating the voxel's response did not yield good decoding scores, suggesting that information may reside in the variability of HDR shapes. Using all the values from the deconvolved HDR also showed low performance, which could be due to an over-fitting problem with the large data dimensionality. When using either positive or negative peak amplitude of the deconvolved HDR, high decoding performance could be achieved for both the 500ms and the 100ms onset differences. The high accuracy even for the 100ms difference, given that the signal was sampled at a TR of 250ms and 2×2×3-mm voxels, implies a possibility of spatiotemporally hyper-resolution decoding. Furthermore, both down-sampling and smoothing did not affect the decoding accuracies very much. These results suggest a complex spatiotemporal relationship between the multi-voxel pattern of the BOLD response and the population activation of neuronal columns. The demonstrated possibility of decoding stimulations for columnar-level organization with 100-ms onset difference using lower resolution imaging data may broaden the scope of application of the BOLD fMRI.

Axonal electrovisiogram as an electrophysiological test to evaluate optic nerve and inner retina electrical potentials: findings in normal subjects

To standardize and validate the technique of axonal electrovisiogram (AxEvg), defining its normative values and parameters and characterizing its findings in normal individuals. We enrolled 140 normal individuals (280 eyes) divided into seven groups according to age, each one with 10 males and 10 females. The technique was based on monocular visual stimulation by a 0 dB intensity bright flash on Ganzfeld bowl at a presentation rate of 1.4 Hz. Golden cup electrodes were used and electrical waves were acquired after artifact rejection. For each amplitude and implicit time peak we calculated the mean, median, pattern deviation, minimum and maximum values and 95% confidence interval. Monocular visual stimulation with bright flash under mesopic conditions was the standard technical procedure established. The normal AxEvg waveform consists of an initial positive wave (named P1, with mean amplitude of 2.0 mV and mean implicit time peak of 23.1 ms) followed by a negative wave (named N1, with mean amplitude of -3.9 mV and mean implicit time peak of 41.4 ms). No significant differences were observed between males and females or between right and left eyes, but there was an increased P1 and N1 implicit time peaks according to age. Implicit time characteristics suggest that P1 wave represents an optic nerve electrical potential and N1 wave represents an inner retinal layers potential. AxEvg can be considered a pre-chiasmatic visual evoked potential capable to reliably record the electrical activity of optic nerve and inner retina. The findings suggest that AxEvg may be useful as an electrophysiological test in the diagnosis of neuroretinal diseases.

A longitudinal functional MRI study of non-arteritic anterior ischaemic optic neuropathy patients

BackgroundNon-arteritic anterior ischaemic optic neuropathy (NA-AION) can cause disabling visual loss and traditionally, visual prognosis has been considered poor, although recent studies have demonstrated improvements in visual acuity in about...

Congenital Achiasma and See-Saw Nystagmus in VACTERL Syndrome

A 29-year-old man with vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal defects, and limb defects (VACTERL) presented with headache, photophobia, and worsening nystagmus. He had near-normal visual acuity and visual fields, absent stereopsis, and see-saw nystagmus. Brain MRI revealed a thin remnant of the optic chiasm but normal-sized optic nerves. Functional MRI during monocular visual stimulation demonstrated non-crossing of the visual evoked responses in the occipital cortex, confirming achiasma. These findings have not previously been reported in VACTERL.

Molecular imaging reveals unique degenerative changes in experimental glaucoma

Experimentally induced changes in the central visual pathway were studied by using positron emission tomography in monkeys with unilateral hypertension glaucoma. In 2-[18F]fluoro-2-deoxy-glucose studies, monocular visual stimulation of the affected eye yielded significantly reduced neural responses in the occipital visuocortical areas. The response reduction was limited to the visual cortex ipsilateral to the affected eye, indicating the unique vulnerability of ipsilateral visual cortex in experimental unilateral glaucoma. In addition, in [11C]PK11195 positron emission tomography and immunohistochemical studies, selective accumulation of activated microglia, a sign of neural degeneration, was found bilaterally in lateral geniculate nuclei. The present findings establish the usefulness of noninvasive molecular imaging for early diagnosis of glaucoma by providing a sharper surrogate end point for an early phase of glaucoma.

BOLD-Perfusion Coupling during Monocular and Binocular Stimulation

Previous studies have suggested that during selective activation of a subset of the zones comprising a columnar system in visual cortex, perfusion increases uniformly in all columns of the system, while increases in oxidative metabolism occur predominantly in the activated columns. This could lead to disproportionately large blood oxygenation level-dependent (BOLD) signal increases for a given flow increase during monocular (relative to binocular) stimulation, due to contributions from columns which undergo large increases in perfusion with little or no change in oxidative metabolism. In the present study, we sought to test this hypothesis by measuring BOLD-perfusion coupling ratios in spatially averaged signals over V1 during monocular and binocular visual stimulation. It was found that, although withholding input to one eye resulted in statistically significant decreases in BOLD and perfusion signals in primary visual cortex, the ratio between BOLD and perfusion increases did not change significantly. These results do not support a gross mismatch between spatial patterns of flow and metabolism response during monocular stimulation.

Timing of ascending and descending visual signals predicts the response mode of single cells in the thalamic nucleus rotundus of the pigeon ( Columba livia)

Neurons of the pigeon's diencephalic n. rotundus were demonstrated to show visual responses of short and long latency representing ascending signals of the retino–tecto–rotundal system and descending signals from telencephalo–tecto–rotundal fibers. Pigeons thus provide an ideal model to investigate the convergence of ascending and descending visual processing streams at single cell level. Although it is known that rotundal responses of long latency show distinct response characteristics, dependent on the stimulus being presented monocularly or binocularly, the mechanisms underlying these response differences are still unclear. While it is possible that the simultaneity of eye stimulation produces a change of processing, it is also possible that the relative timing and order between ipsilateral and contralateral signals are the decisive variable. To test between both possibilities, we recorded from cells in the pigeon's n. rotundus while providing monocular or binocular visual stimulation and varying the delay and order of eye presentations. We revealed that the precise temporal interaction and order of ascending and descending inputs to the tectum decide about late responses with burst or tonic characteristics. When descending signals reached the tectum before the ascending signals, rotundal cells showed late responses that were characterized by burst activity patterns. When ascending input reached the tectum first, responses with tonic characteristic were observed. These effects might become mediated by intratectal mechanisms, the nucleus ventrolateralis thalami, or the bed nuclei of the tectothalamic tract and might constitute the neural basis of a bihemispheric gating function.

Light Stimulus Frequency Dependence of Activity in the Rat Visual System as Studied With High-Resolution BOLD fMRI

The neurophysiology of the rodent visual system has mainly been investigated by invasive and ex-vivo techniques providing fragmented data. This area of research has been deprived of functional MRI studies based on blood oxygenation level dependent (BOLD) contrast, which allows a whole brain approach with a high spatial and temporal resolution. In the present study, we looked at the neurovascular response properties of the visual system of the pigmented rat, focusing on the visual cortex (VC), the superior colliculus (SC) and the flocculus-paraflocculus of the cerebellum (FL-PFL), using BOLD fMRI under domitor anesthesia. Visual stimulation was performed monocularly or binocularly while flashing light from a strobe unit was presented. For each structure, we assessed the flashing frequency that evoked the optimal BOLD response: Neither the VC nor the FL-PFL displayed frequency dependence during monocular visual stimulation, but were most sensitive to low frequencies (1-5 Hz) when flashing light was provided binocularly. The SC responded optimally to high flashing rates (8-12 Hz) during both monocular and binocular stimulation. The signal intensity changes in the VC and FL-PFL were locked to the stimulation period, whereas the BOLD response in the SC showed a similar onset but a very slow recovery at offset. The VC and FL-PFL, but not the SC, showed signs of binocular competition. The observed correlation between frequency-dependent responses of different visual areas during binocular visual presentation suggests a functional relationship between the VC and FL-PFL rather than between the SC and FL-PFL.

Optical imaging in cat area 18: Strabismus does not enhance the segregation of ocular dominance domains

While early-onset strabismus leads to clearly segregated domains of the left and the right eye in cat primary visual cortex (area 17), far less is known about experience-dependent plasticity of ocular dominance in area 18. We therefore used optical imaging of intrinsic signals to analyze the influence of strabismus on cortical maps in cat area 18. Monocular visual stimulation of the left and right eye with moving square wave gratings of four different orientations induced patchy activity maps. Unlike our previous observations in cat area 17, the monocular activity maps in area 18 of strabismic cats were rather similar so that functional ocular dominance domains were not clearly segregated. Imaging of the 17/18 border region confirmed this observation and revealed a sudden change in the segregation of the left and right eye domains across the border. Our results demonstrate that modified visual input can have different consequences for different visual areas: while the decorrelation of activity between the two eyes (as induced by strabismus) clearly enhances the segregation of ocular dominance domains in cat area 17, area 18 does not show this effect although electrophysiological studies have confirmed that the percentage of binocularly driven neurons is as reduced as in area 17.

Near-infrared spectroscopy of the visual cortex in unilateral optic neuritis

To examine the occipital-lobe activation of patients with optic neuritis using near-infrared spectroscopy. Experimental study. NIRS was performed on five patients with acute unilateral optic neuritis during monocular visual stimulation. As controls, six normal subjects were also tested in the same manner. In the patients with optic neuritis, the changes in the hemoglobin concentrations (oxyhemoglobin, deoxyhemoglobin, and total hemoglobin) in the occipital lobe were found to be markedly reduced when the clinically affected eyes were stimulated compared with the fellow eyes. The response induced by the stimulation of the affected eye was decreased, even when the patient's visual acuity improved to 20/20 in the recovery phase. There was no difference in the concentration changes between the two eyes in the control subjects. NIRS may be useful in detecting visual dysfunction objectively and noninvasively in patients with visual disturbance, especially when used at the bedside.

Quantifying the ontogeny of optokinetic and vestibuloocular behaviors in zebrafish, medaka, and goldfish.

We quantitatively studied the ontogeny of oculomotor behavior in larval fish as a foundation for studies linking oculomotor structure and function with genetics. Horizontal optokinetic and vestibuloocular reflexes (OKR and VOR, respectively) were measured in three different species (goldfish, zebrafish, and medaka) during the first month after hatching. For all sizes of medaka, and most zebrafish, Bode plots of OKR (0.065-3.0 Hz, +/-10 degrees/s) revealed that eye velocity closely followed stimulus velocity (gain > 0.8) at low frequency but dropped sharply above 1 Hz (gain < 0.3 at 3 Hz). Goldfish showed increased gain proportional to size across frequencies. Linearity testing with steps and sinusoids showed excellent visual performance (gain > 0.8) in medaka almost from hatching; but zebrafish and goldfish exhibited progressive improvement, with only the largest equaling medaka performance. Monocular visual stimulation in zebrafish and goldfish produced gains of 0.5 versus <0.1 for the eye viewing a moving versus stationary stimulus pattern but 0.25 versus <0.1 in medaka. Angular VOR appeared much later than OKR, initially at only high accelerations (>200 degrees /s at 0.5 Hz), first in medaka followed by larger (8.11 mm) zebrafish; but it was virtually nonexistent in goldfish. Velocity storage was not observed except for an eye velocity build-up in the largest medaka. In summary, a robust OKR was achieved shortly after hatching in all three species. In contrast, larval fish seem to be unique among vertebrates tested in their lack of significant angular VOR at stages where active movement is required for feeding and survival.

Monocular visual activation patterns in albinism as revealed by functional magnetic resonance imaging.

Human albinism is characterized by a disturbance of the chiasmatic projection system leading to predominant representation of just one eye in the contralateral hemisphere. Patients show congenital nystagmus without perceiving oscillopsia. The purpose of the present study was to demonstrate the consequences of atypical chiasmatic crossing with monocular visual stimulation using functional magnetic resonance imaging (fMRI). Sixteen patients with albinism and fifteen normally pigmented controls were stimulated with a monocular visual activation paradigm using flickering checkerboards. In patients, we observed contralaterally dominated activation of visual cortices correlating to clinical albinism parameters. This confirms albinism as a continuous range of hypopigmentation disorders. Additionally, albinos showed activation of the superior colliculus and of visual motion areas although the stimulus was stationary. Activation of visual motion areas is due probably to congenital nystagmus without a conscious correlate like oscillopsia.

Ocular dominance in anterior visual cortex in a child demonstrated by the use of fMRI

Negative signal changes in the visual cortex have been observed during visual stimulation when performing functional magnetic resonance imaging (fMRI) in children. This report investigated whether the ocular dominance, which has been demonstrated in the contralateral anterior visual cortex in adults, could be observed in a child by the use of fMRI. A 5-year-old child was studied using fMRI at 1.5 T during alternating monocular visual stimulation under sedation with morphine and pentobarbital. The functional images were motion corrected, and statistical parametric maps were made by contrasting the left or right eye stimulation conditions vs the right or left eye stimulation conditions, respectively, at each voxel. Areas with negative signal changes were found on the left anterior visual cortex during monocular visual stimulation of the right eye and vice versa. There was no area with negative or positive signal change on the ipsilateral visual cortex to the stimulated eye and no area with positive signal change on the contralateral visual cortex. Contralateral ocular dominance of anterior visual cortex similar to that of adults was demonstrated in this child with a negative correlation with the visual stimulus. This finding suggests that peripheral visual fields are represented in the anterior visual cortex of 5-year-old children.

Functional Magnetic Resonance Imaging of Eye Dominance at 4 Tesla

We studied eye dominance in visual cortex and lateral geniculate nucleus (LGN) using functional magnetic resonance imaging (fMRI) at a very high magnetic field (4 tesla). Eight normal volunteers were studied with fMRI at 4 tesla during alternating monocular visual stimulation. The acquisition was repeated twice in 4 subjects to confirm reproducibility. In addition, magnetic resonance signal intensities during three conditions (right eye stimulation, left eye stimulation, and control condition) were compared to determine whether the observed area was truly or relatively monocular in 2 subjects. In both the individual and group analyses, the anterior striate cortex was consistently activated by the contralateral eye more than the ipsilateral eye. Additionally, we found evidence that there were areas in the bilateral LGN which were more active during the stimulation of the contralateral eye than during the stimulation of the ipsilateral eye. The activated areas were reproducible, and the mean ratio of the overlapping area was 0.71 for the repeated scans. The additional experiment revealed that the area in the anterior visual cortex could be divided into two parts, one truly monocular and the other relatively monocular. Our finding confirmed previous fMRI results at 1.5 tesla showing that eye dominance was observed in the contralateral anterior visual cortex. However, the eye dominance in the visual cortex was found not only in the most anterior area corresponding to the monocular temporal crescent but also in the more posterior area, presumably showing the greater sensitivity of the temporal visual field (nasal retina) as compared with the nasal visual field (temporal retina) in the peripheral visual field (peripheral retina). In addition, it is suggested that the nasotemporal asymmetry of the retina and the visual fields is represented in the LGN as well as in the visual cortex.

Contralateral monocular dominance in anterior visual cortex confirmed by functional magnetic resonance imaging

PURPOSE: Although it is known that the damage to anterior striate cortex results in temporal peripheral visual field loss of the contralateral eye in patients with cerebral visual disturbance, the monocularity of anterior striate cortex has not been demonstrated in normal living humans. The aim of this study was to investigate whether this could be shown noninvasively using functional magnetic resonance imaging of the human visual cortex. METHODS: Eleven normal volunteers were studied with functional magnetic resonance imaging during alternating monocular visual stimulation using a 1.5 Tesla scanner. The data were motion corrected and spatially normalized to the standard brain. The monocular activation of the visual cortex was compared with the activation by the other eye. RESULTS: In the individual data analysis, contralateral eye dominance was always observed in the anterior striate cortex. In the group analysis from 11 subjects, the area with contralateral eye dominance was found in the most anterior part of primary visual cortex where the calcarine fissure merged with the parieto-occipital sulcus. CONCLUSIONS: This study shows that the contralateral eye dominance of anterior striate cortex can be detected noninvasively with functional magnetic resonance imaging during monocular visual stimulation. The finding confirms that the anterior striate cortex, where the monocular temporal crescent is represented, is primarily monocular, but the fact that greatest density of retinal ganglion cells and photoreceptors is in the nasal hemiretina must also be taken into account when interpreting these results.