Monocular Stimulation Research Articles

Functional MRI Examination of Visual Pathways in Patients with Unilateral Optic Neuritis

The relations between brain areas involved in vision were explored in 8 patients with unilateral acute optic neuritis using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). In all patients monocular stimulation of affected and unaffected eye elicited significantly different activation foci in the primary visual cortex (V1), whereas the foci evoked in the middle temporal visual area (area V5) were similar in size and in delay of blood-oxygen-level-dependent response. DTI analysis documented lower white matter anisotropy values and reduced fibre reconstruction in the affected compared with the unaffected optic nerves. The preserved activation of area V5 observed in all our patients is an interesting finding that suggests the notion of a different sensitivity of the optic pathways to inflammatory changes.

Effects of monocular deprivation on the spatial pattern of visually induced expression of c-Fos protein

We studied the pattern of expression of a protein product (c-Fos) of immediate-early gene (IEG) in the visual cortex of rats and mice. The basal expression of c-Fos was very low and visual exposure revealed a large number of c-Fos immunopositive cells in the visual cortex. We found that monocular deprivation during the sensitive period of ocular dominance (OD) plasticity significantly changed both the amount and pattern of c-Fos expression upon monocular stimulation of either eye. The number of immunopositive cells in layer IV of binocular subfields of the primary visual cortex (Oc1B) ipsilateral to the stimulated eye was found to be the most sensitive index of the effects of monocular deprivation during the sensitive period, that is, opened eye stimulation induced significantly larger numbers of c-Fos immunopositive cells, whereas closed eye stimulation induced significantly smaller numbers compared with those induced by monocular stimulation in control animals. In the lateral geniculate nucleus and superior colliculus, the pattern of expression of c-Fos following monocular stimulation was not affected by preceding monocular deprivation. Monocular deprivation imposed after the sensitive period did not affect the pattern of induction of c-Fos. Notably, in age-matched old animals that had been raised in total darkness and then experienced monocular deprivation, the distribution and numbers of c-Fos-expressing cells in visual cortex exhibited the same alterations as found in young animals during the sensitive period. These findings suggest that the present activity mapping method using c-Fos as a molecular marker is useful for examining the activity-dependent regulation of cortical plasticity, and provides an alternative method to conventional electrophysiological recording. This method is particularly powerful when applied to knockout or transgenic mice in which sampling biases in electrophysiological recording have been considered inevitable. Furthermore, these findings suggest that c-Fos is involved in OD plasticity as an IEG that transfers neuronal activity to late gene expression.

Revealing human ocular dominance columns using high-resolution functional magnetic resonance imaging

In this review, I will recall some events at the time when we conducted a high-resolution functional magnetic resonance imaging (fMRI) study mapping ocular dominance columns in humans (Cheng et al., 2001). In particular, I will comment on why and how we had to deal with several key issues in the experimental procedure that we developed in this study, including the adoption of prolonged monocular stimulation, the treatment of large surface veins and the prescription of imaging slice on selected subjects. I will then touch upon several key developments after our work was published and give my thoughts on the challenges that the field of high-resolution fMRI faces.

Same-session functional assessment of rat retina and brain with manganese-enhanced MRI

Manganese-enhanced MRI (MEMRI) is a powerful non-invasive approach for objectively measuring either retina or binocular visual brain activity in vivo. In this study, we investigated the sensitivity of MEMRI to monocular stimulation using a new protocol for providing within-subject functional comparisons in the retina and brain in the same scanning session. Adult Sprague Dawley or Long-Evans rats had one eye covered with an opaque patch. After intraperitoneal Mn(2+) administration on the following day, rats underwent visual stimulation for 8h. Animals were then anesthetized, and the brain and each eye examined by MEMRI. Function was assessed through pairwise comparisons of the patched (dark-adapted) versus unpatched (light-exposed) eyes, and of differentially-stimulated brain structures - the dorsal lateral geniculate nucleus, superior colliculus, and visual cortical regions - contralateral to the patched versus unpatched eye. As expected, Mn(2+) uptake was greater in the outer retina of dark-adapted, relative to light-exposed, eyes (P<0.05). Contralateral to the unpatched eye, significantly more Mn(2+) uptake was found throughout the visual brain regions than in the corresponding structures contralateral to the patched eye (P<0.05). Notably, this regional pattern of activity corresponded well to previous work with monocular stimulation. No stimulation-dependent differences in Mn(2+) uptake were observed in negative control brain regions (P>0.05). Post-hoc assessment of functional data by animal age and strain revealed no significant effects. These results demonstrate, for the first time, the acquisition of functional MRI data from the eye and visual brain regions in a single scanning session.

Binocular Summation Improves Performance to Defocus-Induced Blur

To assess whether there are any advantages of binocular over monocular vision under blur conditions. The effect of defocus, induced by positive lenses, was measured on the pattern reversal visual evoked potential (VEP) and on visual acuity (VA). Monocular (dominant eye) and binocular VEPs were recorded from 13 volunteers (average age, 28 ± 5 years; average spherical equivalent, -0.25 ± 0.73 D) for defocus up to 2.00 D using positive powered lenses. VEPs were elicited using reversing 10 arcmin checks (4 reversals/s). The stimulus subtended a circular field of 7° with 100% contrast and mean luminance 30 cd/m(2). VA was measured under the same conditions using ETDRS charts. All measurements were performed at 1 m viewing distance with best spectacle sphero-cylindrical correction and natural pupils. With binocular stimulation, amplitudes and implicit times of the P100 component of the VEPs were greater and shorter, respectively, in all cases than for monocular stimulation. Mean binocular enhancement ratio in the P100 amplitude was 2.1 in focus, increasing linearly with defocus to be 3.1 at +2.00 D defocus. Mean peak latency was 2.9 ms shorter in focus with binocular than for monocular stimulation, with the difference increasing with defocus to 8.8 ms at +2.00 D. As for the VEP amplitude, VA was always better with binocular than with monocular vision, with the difference being greater for higher retinal blur. Both subjective and electrophysiological results show that binocular vision ameliorates the effect of defocus. The increased binocular facilitation observed with retinal blur may be due to the activation of a larger population of neurons at close-to-threshold detection under binocular stimulation.

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...

Monocular and binocular steady-state flicker VEPs: frequency–response functions to sinusoidal and square-wave luminance modulation

Steady-state VEPs to full-field flicker (FFF) using sinusoidally modulated light were compared with those elicited by square-wave modulated light across a wide range of stimulus frequencies with monocular and binocular FFF stimulation. Binocular and monocular VEPs were elicited in 12 adult volunteers to FFF with two modes of temporal modulation: sinusoidal or square-wave (abrupt onset and offset, 50% duty cycle) at ten temporal frequencies ranging from 2.83 to 58.8 Hz. All stimuli had a mean luminance of 100 cd/m(2) with an 80% modulation depth (20-180 cd/m(2)). Response magnitudes at the stimulus frequency (F1) and at the double and triple harmonics (F2 and F3) were compared. For both sinusoidal and square-wave flicker, the FFF-VEP magnitudes at F1 were maximal for 7.52 Hz flicker. F2 was maximal for 5.29 Hz flicker, and F3 magnitudes are largest for flicker stimulation from 3.75 to 7.52 Hz. Square-wave flicker produced significantly larger F1 and F2 magnitudes for slow flicker rates (up to 5.29 Hz for F1; at 2.83 and 3.75 Hz for F2). The F3 magnitudes were larger overall for square-wave flicker. Binocular FFF-VEP magnitudes are larger than those of monocular FFF-VEPs, and the amount of this binocular enhancement is not dependant on the mode of flicker stimulation (mean binocular: monocular ratio 1.41, 95% CI: 1.2-1.6). Binocular enhancement of F1 for 21.3 Hz flicker was increased to a factor of 2.5 (95% CI: 1.8-3.5). In the healthy adult visual system, FFF-VEP magnitudes can be characterized by the frequency-response functions of F1, F2 and F3. Low-frequency roll-off in the FFF-VEP magnitudes is greater for sinusoidal flicker than for square-wave flicker for rates ≤ 5.29 Hz; magnitudes for higher-frequency flicker are similar for the two types of flicker. Binocular FFF-VEPs are larger overall than those recorded monocularly, and this binocular summation is enhanced at 21.3 Hz in the mid-frequency range.

Efecto de la cirugía de estrabismo de larga evolución en los potenciales evocados visuales binoculares

Purpose To analyse the effect of surgery on binocular visual evoked potential (BVEP) in adults with longstanding strabismus. Methods A prospective study was performed on 40 patients with a history of longstanding strabismus. Visual evoked potentials to binocular and monocular pattern reversal stimulation were recorded before surgery and 3 months after surgery. Binocular visual function was analysed by Worth and TNO tests before and after surgery. Results We did not find any differences between deviation and BVEP postoperatively (P = 0.82). The mean of BVEP and the percentage of increment of the BVEP response (10.5 and 27.14%) were larger postoperatively, than preoperatively (9.87 and 16.6%), P = 0.32 and P = 0.17, respectively. There were differences in the TNO results after surgery (P = 0.03) and when compared with postoperative deviation (P = 0.02), but not between TNO and BVEP postoperatively (P = 0.29). There were differences in the Worth results after surgery, and comparing with deviation and BVEP (P = 0.00, P = 0.01 and P = 0.07). Conclusions Surgery in adults with longstanding strabismus could improve the deviation and seemed to improve BVEP response, but this point could not be confirmed. The results are not enough to show that the BVEP would be an objective test for binocular function evaluation, although there could be a relationship between BVEP and the TNO response.

Interocular amplitude differences of multifocal electroretinograms obtained under monocular and binocular stimulation conditions

To compare the interocular amplitude differences of the multifocal electroretinograms (mfERGs) evoked by either monocular or binocular stimulation in healthy subjects with good vision. Thirty-five subjects were included in the study. A Roland Consult RETIscan system was used. DTL electrodes were employed. First, the right and left eyes were stimulated separately, then, binocular stimulation was applied. The amplitudes of the scalar products were averaged over five concentric retinal regions (rings). The interocular amplitude differences were 21.55% (SD: ±12.72) under monocular conditions and 18.69% (SD: ±11.64) under binocular conditions. No significant differences were found between the amplitudes and variability values obtained under either monocular or binocular stimulation. Our results provided no evidence for the advantage of either binocular or monocular stimulating conditions in obtaining mfERGs. A considerable side difference was found between the mfERGs of the two eyes in almost all individual cases.

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.

The effect of physical effort on retinal activity in the human eye: rod and cone flicker electroretinogram studies

The aim of our study was to assess the effect of physical exercise with increasing intensity on neuroretinal activity in healthy subjects (n = 30). We analysed the amplitude and implicit time of b-wave electroretinogram (ERG) responses in two experiments: (1) for a scotopic blue 10 Hz flicker stimulus (rod-mediated responses), and (2) for a photopic white 30 Hz flicker stimulus (cone-mediated responses). Using a cycloergometer, three 10-minute effort-tests with increasing intensity were performed. Each participant was assigned individual workload values (W) below the lactate threshold (40% VO(2)max), at the lactate threshold (60-65% VO(2)max) and above the lactate threshold (80% VO(2)max). Five ERG recordings were taken: (1) before, (2-4) immediately after the three subsequent efforts and (5) 1 hour after the completion of the last effort. The right eye was selected for monocular stimulation in both experiments. After the first effort (40% VO(2)max), we observed an increased amplitude (p < 0.001) and decreased implicit time of the b-wave (p < 0.01) in cone-mediated responses, and no significant effects in rod-mediated responses. Despite the increase in effort intensity, the cone b-wave amplitude remained unchanged, whereas the rod b-wave amplitude significantly decreased after the subsequent efforts (p < 0.001). Rod-mediated responses were more susceptible to effort-induced homeostasis disruptions than the cone-mediated responses. The application of ERGs may be used as neurophysiological criteria in defining the cardiovascular status of the physical performance.

Speed of Visual Sensorimotor Processes and Conductivity of Visual Pathway in Volleyball Players

Speed of Visual Sensorimotor Processes and Conductivity of Visual Pathway in Volleyball Players Volleyball is a dynamic game which requires a high level of visual skills. The first aim of this study was to investigate the several aspects of reaction times (RT) to visual stimuli in volleyball players (12) compared to non-athletic subjects (12). By using the tests included in the Vienna Test System (Schuhfried, Austria), simple reaction time (SRT), choice reaction time (CRT) and peripheral reaction time (PRT) were examined. The second aim of this study was to assess the neurophysiological basis of early visual sensory processing in both examined groups. We measured two sets of pattern-reversal visual evoked potentials (VEPs) during monocular central field stimulation (Reti Scan, Roland Consult, Germany). The latencies of waves N75, P100 and N135 were determined. We observed significantly shorter (p&lt;0.05) total reaction time to stimuli appearing in the central and peripheral field of vision in the volleyball players compared to non-athletes. With regard to SRT and CRT the main differences between the groups appeared in pre-motor reaction times. Volleyball players had shorter VEPs P100 wave latencies (p&lt;0.05) than the non-athlete group. The results indicate faster signal transmission in visual pathways in athletes than in non-athletes. This fact can be attributed to the effect of rapid visual-activity-demanding sports on the central nervous system.

Effect of surgery on longstanding strabismus on binocular visual evoked potential

PurposeTo analyse the effect of surgery on binocular visual evoked potential (BVEP) in adults with longstanding strabismus. MethodsA prospective study was performed on 40 patients with a history of longstanding strabismus. Visual evoked potentials to binocular and monocular pattern reversal stimulation were recorded before surgery and 3 months after surgery. Binocular visual function was analysed by Worth and TNO tests before and after surgery. ResultsWe did not find any differences between deviation and BVEP postoperatively (P=0.82). The mean of BVEP and the percentage of increment of the BVEP response (10.5 and 27.14%) were larger postoperatively, than preoperatively (9.87 and 16.6%), P=0.32 and P=0.17, respectively. There were differences in the TNO results after surgery (P=0.03) and when compared with postoperative deviation (P=0.02), but not between TNO and BVEP postoperatively (P=0.29). There were differences in the Worth results after surgery, and comparing with deviation and BVEP (P=0.00, P=0.01 and P=0.07). ConclusionsSurgery in adults with longstanding strabismus could improve the deviation and seemed to improve BVEP response, but this point could not be confirmed. The results are not enough to show that the BVEP would be an objective test for binocular function evaluation, although there could be a relationship between BVEP and the TNO response.

Associative pairing involving monocular stimulation selectively mobilizes a subclass of GABAergic interneurons in the mouse visual cortex

Levels of gamma-aminobutyric acid (GABA) and its synthesizing enzyme in cerebral cortex are regulated by sensory experience. Previously we found that associative pairing of vibrissae stimulation and tail shock results in upregulation of GABAergic markers in the mouse barrel cortex. In order to ascertain whether GABAergic upregulation also accompanies associative pairing in other sensory modalities, we examined the mouse visual cortex after analogous training with visual stimulus. During pairing, visual stimulus (CS) was coupled with a tail shock (UCS). We examined the density of cells expressing glutamic acid decarboxylase (GAD) and parvalbumin (PV) in monocular and binocular segments of the primary visual cortex (V1). The auditory cortex was used as a control. After monocular training, the density of cells expressing GAD rose significantly in the monocular segment of V1 contralateral to the stimulated eye, compared with the opposite hemisphere. This effect was due to the association of CS and UCS, as no changes were found after visual stimulation alone or in the auditory cortex. No changes were noted in the density of PV(+) neurons, so the effect was attributed to GAD(+)/PV(-) neurons. Mobilization of a specific subclass of GABAergic cells, observed after associative pairing in the somatosensory and visual cortices, may reflect the necessity to restrict the activity of circuits involved in sensory association.

Microsaccades under monocular viewing conditions

Among the eye movements during fixation, the function of small saccades occuring quite commonly at fixation is still unclear. It has been reported that a substantial number of these microsaccades seem to occur in only one of the eyes. The aim of the present study is to investigate microsaccades in monocular stimulation conditions. Although this is an artificial test condition which does not occur in natural vision, this monocular presentation paradigm allows for a critical test of a presumptive monocular mechanism of saccade generation. Results in these conditions can be compared with the normal binocular stimulation mode. We checked the statistical properties of microsaccades under monocular stimulation conditions and found no indication for specific interactions for monocularly detected small saccades, which might be present if they were based on a monocular physiological activation mechanism.

Study of visual evoked potentials in diabetics without retinopathy: correlations with clinical findings and polyneuropathy

To evaluate central optic pathways' involvement in diabetics, visual evoked potentials (VEP), in particular the latency of positive peak (LP100), were studied in 35 patients without retinopathy (4 insulin-dependent, 31 non-insulin-dependent) and 35 normal controls using reversal pattern stimulation. LP100 was significantly delayed in diabetics at both binocular and monocular stimulation. Furthermore, the delay in LP100 was significantly longer in the diabetics with polyneuropathy than in those without, particularly after binocular stimulation. A positive correlation was found between latencies of VEP and HbA1, duration of disease, and neurologic score. VEP measurement seems a simple and sensitive method for detecting early alterations in central optic pathways in diabetics.

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.

Ensemble cortical responses to rival visual stimuli: Effect of monocular transient

Binocular rivalry is a fascinating perceptual phenomenon that has been characterized extensively at the psychophysical level. However, the underlying neural mechanism remains poorly understood. In particular, the role of the early visual pathway remains controversial. In this study, we used voltage-sensitive dye imaging to measure the spatiotemporal activity patterns in cat area 18 evoked by dichoptic orthogonal grating stimuli. We found that after several seconds of monocular stimulation with an oriented grating, an orthogonal stimulus to the other eye evoked a reversal of the cortical response pattern, which may contribute to flash suppression in perception. Furthermore, after several seconds of rival binocular stimulation with unequal contrasts, transient increase in the contrast of the weak stimulus evoked a long-lasting cortical response. This transient-triggered response could contribute to the perceptual switch during binocular rivalry. Together, these results point to a significant contribution of early visual cortex to transient-triggered switch in perceptual dominance.

Influence of narcotics on luminance and frequency modulated visual evoked potentials in rats

Quantification of visual function is essential for the impact of disease models and their treatment. Recently, we introduced a chronic implant model to record visual evoked potentials (VEP) in awake Brown-Norway rats. Here, we investigated the hemispheric distribution of VEP after monocular stimulation, the chronic electrode implantation and the influence of commonly used anesthetics. Potentials were recorded by electrodes, implanted epidurally over the superior colliculus. The entire visual field of the rat was stimulated. Flicker stimuli were modulated in luminance with a modulation depth from 5 to 80% at 7.5 Hz and flashes with a modulation depth of >95% in a frequency range of 2.9-38 Hz. Recordings were constant over 9 days. When one eye was blinded, the potentials recorded from the contralateral side were not affected, while the potentials of the ipsilateral side were markedly reduced. Further, potentials of awake animals were compared with those receiving general anesthetics. For one group of rats (n = 8), we administered isoflurane by inhalation in five concentrations. Four different groups (n = 7-11) were given choralhydrate (200 and 400 mg/kg) and the combination of ketamine/xyaline (65/7 or 130/14 mg/kg, respectively) intraperitoneally. Isoflurane depressed the VEP in a concentration-dependent manner. Treatment with chloralhydrate and ketamine/xyaline increased the VEP at low concentrations and depressed it in high concentrations. The new VEP paradigm assesses distinct qualities of contrast vision in rats. All tested narcotics alter VEP amplitudes and can be avoided.