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Abnormal visual experience during the critical period can cause deficits in visual function, such as amblyopia. High magnesium (Mg 2+ ) supplementary can restore ocular dominance (OD) plasticity, which promotes the recovery of amblyopic eye acuity in adults. However, it remains unsolved whether Mg 2+ could recover binocular vision in amblyopic adults and what the molecular mechanism is for the recovery. We found that in addition to the recovery of OD plasticity, binocular integration can be restored under the treatment of high Mg 2+ in amblyopic mice. Behaviorally, Mg 2+ -treated amblyopic mice showed better depth perception. Moreover, the effect of high Mg 2+ can be suppressed with transient receptor potential melastatin-like 7 (TRPM7) knockdown. Collectively, our results demonstrate that high Mg 2+ could restore binocular visual functions from amblyopia. TRPM7 is required for the restoration of plasticity in the visual cortex after high Mg 2+ treatment, which can provide possible clinical applications for future research and treatment of amblyopia., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

The endogenous neurotransmitter acetylcholine (ACh) is known to affect the excitatory/inhibitory (E/I) balance of primate visual cortex, enhancing feedforward thalamocortical gain while suppressing corticocortical synapses. Recent advances in the study of the human visual system suggest that ACh is a likely component underlying interocular interactions. However, our understanding of its precise role in binocular processes is currently lacking. Here we use binocular rivalry as a probe of interocular dynamics to determine ACh's effects, via the acetylcholinesterase inhibitor (AChEI) donepezil, on the binocular visual system. A total of 23 subjects (13 male) completed two crossover experimental sessions where binocular rivalry measurements were obtained before and after taking either donepezil (5 mg) or a placebo (lactose) pill. We report that enhanced cholinergic potentiation attenuates perceptual suppression during binocular rivalry, reducing the overall rate of interocular competition while enhancing the visibility of superimposition mixed percepts. Considering recent evidence that perceptual suppression during binocular rivalry is causally modulated by the inhibitory neurotransmitter GABA, our results suggest that cholinergic activity counteracts the effect of GABA with regards to interocular dynamics and may modulate the inhibitory drive within the visual cortex. SIGNIFICANCE STATEMENT Our research demonstrates that the cholinergic system is implicated in modulating binocular interactions in the human visual cortex. Potentiating the transmission of acetylcholine (ACh) via the cholinergic drug donepezil reduces the extent to which the eyes compete for perceptual dominance when presented two separate, incongruent images., (Copyright © 2020 the authors.)

Purpose: To study the outcome of botulinum toxin (BTX) treatment (group 1) in partially accommodative esotropia with high accommodative convergence/accommodation (AC/A) ratio, in comparison with bilateral medial rectus muscles recessions and posterior fixation (group 2)., Methods: In a retrospective comparative study, children aged 3-8 years old treated between 2011 and 2016, with partially accommodative esotropia with high AC/A ratio, deviation at distance of 10 prism diopters or more, and at least 1 year of follow-up, were included. Visual acuity, alternate prism and cover test, stereoacuity, biomicroscopy, and cycloplegic retinoscopy were carried out at initial, baseline visit, 6 months and 1 year after BTX injection or surgery. Main outcome variables were deviation at distance and near, improvement in stereoacuity, and percentage of success. We used multiple regression or proportional odds analysis to control for potential confounding variables., Results: Of 95 patients, 84 were eligible, 48 children in group 1 and 36 in group 2. Deviation and stereoacuity were similar in the two groups at 6 months, but significantly better in the BTX group at 1 year (median distance deviation 0 prism diopters vs 5 prism diopters, p<0.01), although differences were not clinically relevant. Percentage of success was also significantly better only at 1 year (93% vs 72%, p = 0.01). Change in distance-near disparity was not significantly different in the two groups in the period of study., Conclusions: Botulinum toxin could be superior to, or as effective as surgery, at middle term, in the treatment of partially accommodative esotropia with high AC/A ratio., Competing Interests: The authors have declared that no competing interests exist.

Binocular rivalry is a classic experimental tool to probe the neural machinery of perceptual awareness. During rivalry, perception alternates between the two eyes, and the ebb and flow of perception is modeled to rely on the strength of inhibitory interactions between competitive neuronal populations in visual cortex. As a result, rivalry has been suggested as a noninvasive perceptual marker of inhibitory signaling in visual cortex, and its putative disturbance in psychiatric conditions, including autism. Yet, direct evidence causally implicating inhibitory signaling in the dynamics of binocular rivalry is currently lacking. We previously found that people with higher GABA levels in visual cortex, measured using magnetic resonance spectroscopy, have stronger perceptual suppression during rivalry. Here, we present direct causal tests of the impact of GABAergic inhibition on rivalry dynamics, and the contribution of specific GABA receptors to these dynamics. In a crossover pharmacological design with male and female adult participants, we found that drugs that modulate the two dominant GABA receptor types in the brain, GABA A (clobazam) and GABA B (arbaclofen), increase perceptual suppression during rivalry relative to a placebo. Crucially, these results could not be explained by changes in reaction times or response criteria, as determined through rivalry simulation trials, suggesting a direct and specific influence of GABA on perceptual suppression. A full replication study of the GABA B modulator reinforces these findings. These results provide causal evidence for a link between the strength of inhibition in the brain and perceptual suppression during rivalry and have implications for psychiatric conditions including autism. SIGNIFICANCE STATEMENT How does the brain accomplish perceptual gating? Here we use a direct and causal pharmacological manipulation to present insight into the neural machinery of a classic illusion of perceptual awareness: binocular rivalry. We show that drugs that increase GABAergic inhibition in the brain, clobazam (GABA A modulator) and arbaclofen (GABA B modulator), increase perceptual suppression during rivalry relative to a placebo. These results present the first causal link between GABAergic inhibition and binocular rivalry in humans, complementing classic models of binocular rivalry, and have implications for our understanding of psychiatric conditions, such as autism, where binocular rivalry is posited as a behavioral marker of disruptions in inhibitory signaling in the brain., (Copyright © 2019 the authors.)

Nonhuman animal models have demonstrated that selective serotonin reuptake inhibitors (SSRIs) can enhance plasticity within the mature visual cortex and enable recovery from amblyopia. The aim of this study was to test the hypothesis that the SSRI citalopram combined with part-time patching of the fellow fixing eye would improve amblyopic eye visual acuity in adult humans. Following a crossover, randomized, double-blind, placebo-controlled design, participants completed two 2-week blocks of fellow fixing eye patching. One block combined patching with citalopram (20 mg/day) and the other with a placebo tablet. The blocks were separated by a 2-week washout period. The primary outcome was change in amblyopic eye visual acuity. Secondary outcomes included stereoacuity and electrophysiological measures of retinal and cortical function. Seven participants were randomized, fewer than our prespecified sample size of 20. There were no statistically significant differences in amblyopic eye visual acuity change between the active (mean ± SD change = 0.08 ± 0.16 logMAR) and the placebo (mean change = -0.01 ± 0.03 logMAR) blocks. No treatment effects were observed for any secondary outcomes. However, 3 of 7 participants experienced a 0.1 logMAR or greater improvement in amblyopic eye visual acuity in the active but not the placebo blocks. These results from a small sample suggest that larger-scale trials of SSRI treatment for adult amblyopia may be warranted. Considerations for future trials include drug dose, treatment duration, and recruitment challenges. This study was preregistered as a clinical trial (ACTRN12611000669998).

Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: -0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (-0.167 logMAR; 95% CI: -0.226 to -0.108; p < 0.001) and placebo (-0.194 logMAR; 95% CI: -0.254 to -0.133; p < 0.001) groups. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support other recent clinical studies suggesting that improvement of vision can be accomplished in adults with amblyopia.

Purpose: Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity., Methods: Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls., Results: Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density., Conclusions: Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus.

Early sensory experience instructs the maturation of neural circuitry in the cortex. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.

A key model for examining the activity-dependent development of primary visual cortex (V1) involves the imbalance in activity between the two eyes induced by monocular deprivation (MD). MD early in life causes dramatic changes in the functional and structural organization of mammalian visual cortex. The molecular signals that mediate the effects of MD on the development of visual cortex are not well defined. Neurotrophic factors are important in regulating the plasticity of visual cortex, but the choice of an appropriate growth factor as well as its delivery has proven difficult. Although vascular endothelial growth factor-B (VEGF-B) is a homolog of the angiogenic factor VEGF-A, it has only minimal angiogenic activity, raising the question of whether this factor has other (more relevant) biological properties. Intrigued by the possibility that VEGF family members affect neuronal cells, we explored whether VEGF-B has a role in the nervous system. In rats, VEGF-B infusion during monocular deprivation (MD) counteracted the normally occurring ocular dominance (OD) shift toward the non-deprived eye so that the deprived eye dominated the VEGF-B-treated cortex after MD. In particular, VEGF-B counteracted the effects of MD without causing detectable alterations in spontaneous discharge or behavior. In conclusion, the simultaneous analysis of visual cortical cell discharge and ocular dominance plasticity suggests that VEGF-B has important effects on the functional architecture of the visual cortex. Therefore, VEGF-B is a new candidate trophic challenge molecule for the visual cortex., (Copyright © 2013. Published by Elsevier Ltd.)

Purpose: To assess the suitability of galantamine for the symptomatic treatment of post-traumatic oculomotor (III) and trochlear (IV) nerve palsy., Material and Methods: The routine ophthalmic and strabological examination was performed in five patients (4 females and 1 male) at the age of 31 to 57 years (mean 40.7) with the post-traumatic ophthalmic complications. Due to the unilateral oculomotor and trochlear nerve palsy, which had not resolved within 2-6 (mean duration of 4 months) months following traffic accident, galantamine was used. Nivalin and Reminyl were administered in iontophoresis and orally, respectively, for 10-18 months (mean duration of 14 months). The ocular muscle motion exercises and prism correction were also used., Results: The increased range of ocular motion (100%), reducing of the angle of strabismus horizontally (40%) and vertically (60%), statistically significant extension of palpebral fissure (60%), and regression of diplopia (80% total without correction) were observed. The binocular vision after treatment in the free- and instrument-space environment were also improved (100% simultaneous perception, fusion 80%, stereopsis 60%)., Conclusions: The early galantamine administration in patient with n. III and n. IV post-traumatic palsy accelerates the resolution of post-traumatic ophthalmic symptoms. It is an effective treatment which offers the elimination of strabismus, diplopia and ptosis, at the same time improvings ocular movements and binocular vision. galantamine, post-traumatic nerve palsy, oculomotor and trochlear nerves.

Purpose: To investigate nystagmus and other visual system abnormalities among children exposed to opiates and benzodiazepines in utero., Methods: Retrospective case series comprising clinical examination and case note review of 25 children with nystagmus and reduced vision who were exposed to controlled drugs during pregnancy., Results: Twenty-four children were exposed to opiates, of whom 13 were also exposed to diazepam. One child was exposed to diazepam alone. All children had horizontal nystagmus, which was either fine pendular or jerk type. The nystagmus had a latent element in 4 children and 8 adopted a compensatory head posture. Where the time of onset of nystagmus was known, it was always prior to 6 months of age. At least 9 children (36%) had delayed visual maturation. The mean initial logarithm of the minimum angle of resolution binocular best-corrected visual acuity (BCVA) was 0.54 at an average of 22 months of age. Thirteen children were followed up for 6 months or longer and their BCVA improved to 0.4 at an average age of 48 months. The nystagmus was clinically improved in only 5 patients. Electroretinogram testing was normal in the 4 children tested. The only ocular structural abnormality was binocular optic nerve hypoplasia in 2 children., Conclusion: Exposure to opiates and benzodiazepines in utero may be associated with permanent nystagmus and reduced visual acuity. This is most likely the result of insult(s) to the central nervous system rather than the eyes., (Copyright 2012, SLACK Incorporated.)

Purpose: Visually guided ocular growth is facilitated by scleral extracellular matrix remodeling at the posterior pole of the eye. Coincident with scleral remodeling, significant changes in choroidal morphology, blood flow, and protein synthesis have been shown to occur in eyes undergoing ocular growth changes. The current study is designed to identify gene expression changes that may occur in the choroid/retinal pigment epithelium (RPE) of marmoset eyes during their compensation for hyperopic defocus as compared to eyes compensating for myopic defocus., Methods: Total RNA was isolated from choroid/RPE from four common marmosets (Callithrix jacchus) undergoing binocular lens treatment using extended wear soft contact lenses of equal magnitude but opposite sign (+/-5 diopter [D]). After reverse transcription, cDNA was labeled and hybridized to a human oligonucleotide microarray and gene transcript expression profiles were determined. Real-time polymerase chain reaction (PCR) and western blot analysis were used to confirm genes and proteins of interest, respectively., Results: Microarray analyses in choroid/RPE indicated 204 genes were significantly changed in minus lens-treated as compared with plus lens-treated eyes (p<0.05, Student's t-test). Differential choroid/RPE expression of protein tyrosine phosphatase, receptor type, B (PTPRB), transforming growth factor beta-induced (TGFBI), and basic fibroblast growth factor 2 (FGF-2) were confirmed by real-time PCR. TGFBIp was confirmed at the protein level by western blot analysis in marmoset and human cornea, choroid/RPE, and sclera., Conclusions: The present study demonstrated that significant gene expression changes occur in the marmoset choroid/RPE during visually guided ocular growth. The identification of novel candidate genes in choroid/RPE of marmoset eyes actively accelerating or decelerating their rates of ocular elongation may elucidate the choroidal response during the regulation of postnatal ocular growth and may lead to the identification of choroid/RPE signaling molecules that participate in scleral remodeling.

Objective: With MEG and EEG the effect of perinatal dioxin load of 38 healthy 7- to 12-year-old children was studied to assess possible disturbances of visual development., Methods: Latencies and amplitudes of the motion (N2 with subcomponents) and oddball responses (N200 and P3b) were analysed after age correction., Results: With increasing load, latencies increased and the amplitudes of the oddball components tended to be reduced. The latency increase between the high- and low-loaded children was about 13 ms (P<0.004) and the oddball response showed an amplitude decrease of 12% (P=0.009)., Conclusions: It may be concluded that, during the end-80s/early-90s, exposure to background levels in industrialized regions seems to have resulted in small underdevelopment or damage to visual motion processing and visual cognition., Significance: Since dioxin pollution by incinerators still exists in many regions in developing countries and also still, although at a smaller scale, in the industrialized world, perinatal loads of similar magnitude and possibly more as measured in this study may occur and as a consequence might affect the developing brain.

Recent data on alterations of the endogenous cannabinoid system in schizophrenia have raised the question of its functional role in this disease. The psychoactive compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been shown to induce psychotic symptoms, but it is unknown to what extend prodromal states of psychoses are reflected by these experimental approaches. This study compares four groups of subjects: antipsychotic-naïve patients suffering from acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the prodromal state (IPS), healthy controls without any pharmacological intervention (HC) and a second group of healthy volunteers who were orally administered synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received the experimental drug. All subjects were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The latter represents a sensitive measure of impaired visual information processing that manifests in various experimental and naturally occurring psychotic states. BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed significantly to HC. The BPRS revealed no significant difference between HC-THC and IPS while both were significantly different from SZ and HC, respectively. Our results suggest that Delta9-THC-induced altered states of consciousness may serve as a useful tool for modeling psychotic disorders, particularly their prodromal states. Furthermore, they provide insight into the perceptual and psychopathological alterations induced by Delta9-THC, which is essential for the understanding of the pro-psychotic effects of herbal cannabis preparations with highly enriched Delta9-THC content.

The topographic binocular maps in the optic tectum of Xenopus frogs are notable both for their dramatic plasticity during development and for the high expression of melatonin receptors in the circuitry contributing to those binocular maps. The goal of this study was to determine whether melatonin contributes to the control of binocular tectal plasticity. During development, rotation of one eye leads to compensatory rewiring of ipsilateral maps. The effect of 3-4 months of chronic 20 or 200 nM melatonin on this rewiring was tested by electrophysiological mapping. No decrease in plasticity was observed. In adult Xenopus, rotation of one eye normally does not lead to rewiring of the ipsilateral projection, although adults can exhibit plasticity if they have been dark-reared or have been treated as adults with NMDA. We tested whether exposure to 20-200 nM melatonin during and after the normal critical period would similarly extend plasticity. Eye rotation in adults that had been treated with melatonin did not demonstrate retained plasticity. These results show that melatonin does not reduce the normally high plasticity characteristic of young Xenopus nor does it increase the normally low plasticity of adult Xenopus.

Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

Rationale: During binocular rivalry, two incompatible images are presented to each eye and these monocular stimuli compete for perceptual dominance, with one pattern temporarily suppressed from awareness. One variant of stimulus presentation in binocular rivalry experiments is dichoptic stimulus alternation (DSA), when stimuli are applied to the eyes in rapid reversals. There is preliminary report that in contrast with healthy controls, schizophrenic patients can maintain binocular rivalry even at very high DSA rates., Objective: The study was undertaken to investigate whether binocular rivalry survives high rates of DSA induced by the South American hallucinogenic beverage ayahuasca., Methods: Ten individuals who were participating in ayahuasca ceremonials were requested to volunteer for binocular rivalry tests (DSA=0, 3.75, 7.5, 15 and 30 Hz) without and after drinking the brew., Results: Ingestion of ayahuasca increased mean dominance periods both in standard binocular rivalry conditions (no DSA) and tests with DSA. At higher DSA rates (15 and 30 Hz) the total length of dominance periods was longer on the brew., Conclusion: It is discussed that ayahuasca-induced survival of binocular rivalry at high DSA rates may be related to slow visual processing and increased mean dominance periods may result from hallucinogen-induced alteration of gamma oscillations in the visual pathways.

An early theoretical analysis supposed changes in hemispheric integration as the basis of altered state of consciousness induced by psychoactive drugs. Brain imaging studies revealed right cortical activation after administration of hallucinogens. Recent studies on binocular rivalry suggest that interhemispheric switching is the neural substrate of the perceptual oscillations observed during dichoptic stimulus presentation. The current study tested perceptual alternation in ceremonial participants, who ingested the South American hallucinogenic beverage ayahuasca, to examine the claim that there might be changes in interhemispheric function under the influence of hallucinogens. Ingestion of ayahuasca resulted in a decrease of rivalry alternation rates, increased length of one percept and there was evidence of phenomenal fusion. The findings are in line with results of brain activation studies and support the concept of interhemispheric fusion in altered states of consciousness.

Perceptual rivalry is an oscillation of conscious experience that takes place despite univarying. if ambiguous, sensory input. Much current interest is focused on the controversy over the neural site of binocular rivalry, a variety of perceptual rivalry for which a number of different cortical regions have been implicated. Debate continues over the relative role of higher levels of processing compared with primary visual cortex and the suggestion that different forms of rivalry involve different cortical areas. Here we show that the temporal pattern of disappearance and reappearance in motion-induced blindness (MIB) (Bonneh et al, 2001 Nature 411 798-801) is highly correlated with the pattern of oscillation reported during binocular rivalry in the same individual. This correlation holds over a wide range of inter-individual variation. Temporal similarity in the two phenomena was strikingly confirmed by the effects of the hallucinogen LSD, which produced the same, extraordinary, pattern of increased rhythmicity in both kinds of perceptual oscillation. Furthermore. MIB demonstrates the two properties previously considered characteristic of binocular rivalry. Namely the distribution of dominance periods can be approximated by a gamma distribution and, in line with Levelt's second proposition of binocular rivalry, predominance of one perceptual phase can be increased through a reduction in the predominance time of the opposing phase. We conclude that (i) MIB is a form of perceptual rivalry, and (ii) there may be a common oscillator responsible for timing aspects of all forms of perceptual rivalry.

Purpose: To evaluate the effects of a single dose of levodopa on visual cortex, based on functional MRI (fMRI), and on visual function, based on psychophysical tests, in amblyopic and normal subjects., Method: A prospective, randomized trial of a single dose of levodopa (2 mg/kg body weight) was undertaken in an institutional setting in nine normal and six amblyopic subjects, who were assessed at baseline and 90 minutes after levodopa ingestion. fMRI of occipital visual cortex was undertaken with a 1.5T GE MRI scanner utilizing the BOLD contrast technique. fMRI stimuli were two gratings (0.5, 2.0 cycles/degree of visual angle) that counterphased at 4 Hz. fMRI parameters for analysis included AREA and LEVEL of activation and a SUMMED score (AREA x LEVEL). Psychophysical tests included visual acuity, contrast sensitivity, stereoacuity, and binocular fusion., Results: At baseline, AREA of activation (P = .05) and SUMMED score (P = .05) were significantly less in the amblyopic compared to the dominant eyes. Psychophysically, visual acuity and contrast sensitivity were significantly worse in the amblyopic eye. Following levodopa ingestion, there was significant decrease in LEVEL of activation in the amblyopic eye, even though visual acuity showed significant improvement (P = .03). Also, amblyopes showed a significant increase and normals showed some decrease in interocular difference in LEVEL of activation (P = .04)., Conclusion: Unique information was obtained when fMRI was utilized to assess visual cortical function. While levodopa improved visual acuity in the amblyopic eye, it decreased the LEVEL of activation based on fMRI, a counterintuitive finding. The results highlight the value of utilizing fMRI to assess amblyopia and provide new directions for research.

The monocular deprivation model of amblyopia is characterized by a reduction in cortical responses to stimulation of the deprived eye. Although the effects of monocular deprivation on the primary visual cortex have been well characterized physiologically and anatomically, the molecular mechanisms underlying ocular dominance plasticity remain unknown. Previous studies have indicated that the transcription factor adenosine cAMP/Ca(2+) response element-binding protein (CREB) is activated during monocular deprivation. However, it remains unknown whether CREB function is required for the loss of cortical responses to the deprived eye. To address this issue, we used the herpes simplex virus (HSV) to express a dominant negative form of CREB (HSV-mCREB) containing a single point mutation that prevents its activation. Quantitative single-unit electrophysiology showed that cortical expression of this mutated form of CREB during monocular deprivation prevented the loss of responses to the deprived eye. This effect was specific and not related to viral toxicity, because overexpression of functional CREB or expression of beta-galactosidase using HSV injections did not prevent the ocular dominance shift during monocular deprivation. Additional evidence for specificity was provided by the finding that blockade of ocular dominance plasticity was reversible; animals treated with HSV-mCREB recovered ocular dominance plasticity when mCREB expression declined. Moreover, this effect did not result from a suppression of sensory responses caused by the viral infection because neurons in infected cortex responded normally to visual stimulation. These findings demonstrate that CREB function is essential for ocular dominance plasticity.

Purpose: We report a female adult with congenital nystagmus who responded with improved visual function and oculographic parameters after taking the anorexic diet drug Tenuate Dospan (diethylproprionate; Watson Laboratories, Inc., Corona, California)., Methods: Observational case report. Clinical ophthalmic examination and ocular motility recordings were performed before and after administration of the drug Tenuate Dospan., Results: The binocular visual acuity of the patient improved from 20/70 to 20/50, her exotropic deviation decreased from 12 to 4 prism diopters, her stereopsis increased from none to 200 seconds/arc, and her ocular motility recordings showed increased foveation periods and a broadened null zone., Conclusion: For unexplained reasons, the anorexic stimulant Tenuate Dospan "paradoxically" improved the nystagmus and binocular function in this patient with congenital nystagmus. This observation may be the basis for investigation of a new pharmacological treatment approach to patients with congenital nystagmus or strabismus.

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2-3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABA(A) agonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABA(A) agonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABA(A) antagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.

Selectivity to visual stimulus orientation is a basic cortical functional property believed to be crucial for normal vision. Maturation of this neuronal property requires neural activity. Still, it is unclear what might be the molecular basis for such activity-dependent processes and whether activity has an instructive or permissive role in development of orientation selectivity. There is strong evidence that the NMDA subtype of the glutamate receptor regulates activity-dependent mechanisms of ocular dominance plasticity during cortical development. For this reason, we have hypothesized that the NMDA receptor participates in activity-dependent mechanisms that sculpt orientation selectivity of cortical neurons. We used chronic in vivo infusion of antisense oligodeoxynucleotides (ODNs) to suppress NMDA receptor function in primary visual cortex during the period when orientation selectivity develops in ferrets. Chronic suppression of NMDA receptor function prevented the development of orientation and stimulus size selectivity in most cortical cells tested. In contrast, treatment with control sense or missense ODNs did not affect development of orientation selectivity, indicating specificity of effects. Importantly, antisense ODN treatment did not impair visually driven activity, which is required for development to occur. Moreover, orientation selectivity of cortical cells was not disrupted by antisense ODN treatment in mature animals, indicating developmental relevance of the effects. In conclusion, our findings document for the first time that cortical NMDA receptors are essential for the maturation of orientation selectivity. This result supports the notion that activity has an instructive role in sculpting the connections that underlie orientation selectivity in visual cortex.

Purpose: We report a child with retinal dystrophy and congenital (a)periodic alternating nystagmus (APAN) who responded immediately with improved visual function and electrooculographic parameters after taking the psychopharmacologic stimulant Dexedrine Spansule (Glaxo-Smith Kline, NC, USA) as part of treatment for his Attention Deficit Disorder., Design: Interventional case report., Methods: General ophthalmic, ocular motor and sensorimotor examinations and ocular motility recordings were performed before and after administration of the drug Dexedrine Spansule., Results: The patient's binocular visual acuity improved only at 1.5 after medicine hours from 20/63 to 20/50, his exotropic deviation decreased from 25 to 10 prism diopters, his stereopsis increased from none to 800 sec/arc and ocular motility recordings showed increased foveation periods and more and lengthened APAN transition/null zones., Conclusion: For unexplained reasons the stimulant Dexedrine "paradoxically" improved the nystagmus, binocular function and visual acuity in this patient with retinal dystrophy and congenital nystagmus. This observation may be the basis for investigation of a new pharmacological treatment approach to patients with congenital nystagmus or strabismus.

Background: Previous studies have shown an effect of the tranquilizer lorazepam on visual perception. We explored the effects of the drug on binocular vision, visual acuity and accommodation., Subjects and Methods: Twenty-four paid healthy volunteers (13 women, 11 men) were recruited from the University of Strasbourg (mean age: 23.6 years, mean weight: 66.8 Kg). They were randomly assigned to one of two parallel groups of 12 subjects each (a placebo group and a lorazepam 0.038 mg/kg group). Visual acuity was measured for each eye separately (Snellen chart and Parinaud scale). Binocular vision was studied using the cover tests, measurement of the fusional amplitudes (with Berens prisms), and the Duane Scale Test (near point rule) measuring convergence and/or accommodation in centimeters or diopters as a function of age., Results: Regarding vision, there was no lorazepam effect, at either 33 cm or 5 m. An esophoria was observed after the intake of lorazepam (0Delta before intake and 2.8Delta after intake, p=0.001). Both fusional convergence and fusional divergence amplitudes decreased by lorazepam, (p=0.008, and p=0.002). Lorazepam also impaired the near point of convergence but did not affect accommodation., Conclusion: A single dose of lorazepam induces an esophoric oculomotor imbalance and impaired fusional convergence and divergence amplitudes without impairing visual acuity or accommodation.

Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic delta9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The timecourse of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.

The possible effects on psychomotor performance, concentration, attention, and mood of acamprosate (calciumacetylhomotaurinate) were assessed using a randomized, double-blind, cross-over, placebo-controlled design involving 12 healthy male volunteers. Acamprosate 2 g daily per os or placebo was administered for seven days and separated by washout intervals of at least 21 days. Objective tests evaluated psychomotor functions (simple reaction time measurement, binary choice reaction test, computerized visual searching task, sustained attention test). Mood was assessed using the Beck Depression Inventory and the Beschwerde-Liste to assess subjective physical impairment. Additionally, a visual 3-D illusion paradigm was applied to measure the psychotomimetic effect. A dose of acamprosate of 2 g/day for seven days was free of any significant effects on mood, concentration, attention, psychomotor performance and did not produce any subjective sedation, excitation or psychotomimetic effects.

Binocular depth inversion represents an illusion of visual perception, serving to invert the perception of implausible hollow objects, e.g. a hollow face into a normal face. Such inversion occurs frequently, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. The hypothesis was tested that during mild and moderate alcohol withdrawal, and severe and mild alcohol intoxication, the central nervous system is unable to correct implausible perceptual hypotheses. Measurements of binocular depth inversion in perception of three-dimensional objects were performed in 10 patients with severe alcohol intoxication, in 10 subjects with mild alcohol intoxication, in nine patients with moderate alcohol withdrawal treated with carbamazepine, in 10 patients with moderate alcohol withdrawal without any pharmacological treatment, in 11 patients with mild alcohol withdrawal and in 10 healthy volunteers. The binocular depth inversion scores were highly elevated in the severely intoxicated patients group and in the group with moderate withdrawal symptoms without carbamazepine treatment, in comparison to the healthy volunteers. The data demonstrate a strong impairment of binocular depth inversion in moderate alcohol withdrawal and during severe alcohol intoxication. This supports the view that these states may be accompanied by a disorganization of the interaction between sensory input and top-down component. The effects of carbamazepine are discussed.

Diabetic patients routinely have their pupils dilated for fundoscopy as part of the annual review. To assess the ability of diabetic patients to drive after pupillary dilatation we studied 61 diabetic patients (18 IDDM, 43 NIDDM), mean age 54.98 years, before and 1 h after pupillary dilatation with 1% tropicamide. Binocular visual acuity (BVA) and contrast sensitivity were checked without glare, with glare, and with glare and sunglasses. Glare was introduced using a 60 W bulb in all 61 patients and with a 500 W bulb in 37 of these patients. Prior to dilatation all 61 patients had a BVA of 6/9 or better. A significant reduction in BVA was found post-dilatation (p = 0.005) and 4 out of the 61 patients (6.56%) had a post-dilatation BVA of less than 6/9. The 60 W glare source caused a significant reduction in BVA pre-dilatation (p < 0.05), but not the 500 W glare. With glare, post-dilatation BVA reduced further, resulting in 6 and 7 patients having a BVA of less than 6/9 with the 60 W and 500 W glare source, respectively. The addition of sunglasses with glare did not improve the BVA. No patient with a BVA of 6/5 pre-dilatation reduced to less than 6/9 post-dilatation. No significant change in contrast sensitivity was found in any of the test conditions. We conclude that patients who meet the visual legal requirements to drive (BVA < or = 6/9) prior to dilatation may not fulfil them post-dilatation. This has important clinical implications and the time course of the phenomenon requires exploration. Meanwhile, patients need to be warned not to drive after pupillary dilatation when they attend for annual fundoscopic examination, certainly for at least two hours.

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also by an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Herein, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for the understanding of model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulator system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. Neuropsychological results (three-dimensional inversion illusion) in delta 9-tetrahydrocannabinol-intoxicated normal volunteers exhibit strong similarities with data acquired from patients suffering from productive schizophrenic psychoses, regarding disturbances in internal regulation of perceptual processes. The relevance of this finding to a general cognitive dysfunction concept of schizophrenic psychosis is discussed.

In a placebo-controlled experiment comprising 22 healthy men (mean age 27.4 years), we investigated the influence of three breath levels of blood alcohol (BrAC; 0.0%, 0.05% and 0.1%) upon distant visual acuity, stereoacuity, contrast sensitivity, accommodation, resting focus of accommodation and binocular vision. Positive (PRA) and negative accommodation (NRA) and resting focus of accommodation showed no significant changes with increasing BrAC. Compared to the placebo condition, visual acuity and refraction were only significantly affected at a breath alcohol level of 0.1%. Contrast sensitivity, stereoacuity and binocular vision were affected both at BrAC 0.05% and BrAC 0.1%. Only the higher spatial frequencies of contrast sensitivity were affected.

Binocular depth inversion represents an illusion of visual perception. Such inversion does not occur in all cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. We tested the hypothesis that during alcohol withdrawal the human CNS is unable to correct the implausible perceptual hypothesis. Measurements of binocular depth inversion in perception of 3D objects were performed in 10 patients with mild alcohol withdrawal and in 11 healthy volunteers. The binocular depth inversion scores were highly elevated in the patients group in comparison to the healthy volunteers. The data demonstrates a strong impairment of binocular depth inversion in alcohol withdrawal and support the view that alcohol withdrawal may be accompanied by a disorganization of the interaction between sensory input and generation of perceptual hypotheses.

Activity-dependent modifiability of cortical ocular dominance occurs only during early postnatal life, within the so-called "critical period," but not thereafter in adult visual cortex. To examine the role of neurotrophins in the activity- and age-dependent stimulation-induced modifiability of visual cortex, we tested whether intracortical infusion of nerve growth factor could induce ocular dominance plasticity in adult visual cortex. Nerve growth factor was continuously infused, by means of osmotic minipumps, into striate cortex of adult cats for 2 weeks. At the time of minipump implantation, one eyelid of the experimental animals was sutured closed. After 3 weeks of monocular deprivation, the ocular dominance distribution of neurons in the striate cortex was assessed using single unit recording. We found that monocular deprivation imposed on adult animals in conjunction with nerve growth factor infusion causes an ocular dominance shift toward the deprived eye. Although the underlying mechanisms remain uncertain, the results indicate that nerve growth factor can enhance activity-dependent synaptic modification and remodeling in adult visual cortex.

Background: Botulinum toxin injection into the medial rectus has been recommended by several investigators as an alternative to incisional surgery for treatment of patients with congenital (essential infantile) esotropia. Currently, there are no published studies demonstrating both the motor and sensory results of congenital esotropic patients aligned by botulinum toxin., Methods: The author traveled to two medical centers to personally and objectively examine, with standardized testing methods, 12 patients with congenital esotropia who had been aligned for a minimum of 6 months by the age of 2 years by other investigators. The selected patients had been followed for a minimum of 3 years and were of sufficient maturity to reliably respond to sensory testing. A comparison was made between the author's conclusions about the binocularity results of these patients and the assessment of the treating ophthalmologists., Results: Only 6 of the 12 patients demonstrated optimum motor alignment to within 10 prism diopters (PD) of orthophoria at the time of the study. A minimum of 1-month (average, 5 months) post-botulinum injection was found to be necessary to establish this alignment. Only three of these six aligned patients could both fuse and demonstrate gross stereopsis without the assistance of compensatory prisms. These results can be contrasted to a previously reported group of surgically aligned cases in which 66 of 90 patients aligned by 2 years of age could both fuse and demonstrate stereopsis, without any use of compensatory prisms., Conclusion: These results must be considered preliminary. However, alignment by botulinum appears to be less effective in establishing evidence for binocularity than incisional surgery in the treatment of congenital esotropia (P < 0.001).

1. Eye movements were measured in three rhesus monkeys after monocular intravitreal injections of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist. The effects of this drug were tested when the animals were in a completely dark room, when they performed a smooth pursuit task, and when they viewed either a stationary pattern or a full-field optokinetic pattern rotating horizontally. 2. Between 15 and 20 min after the injection, a sustained conjugate spontaneous nystagmus developed in the dark, with the slow-phase movement in the temporal-to-nasal direction with respect to the injected eye. Peak slow-phase velocity ranged from 15 to 45 degrees/s. The nystagmus persisted for at least 1 h but stopped by the next day. 3. In a well-lit room, the nystagmus was completely suppressed, even during monocular viewing with the injected eye. When the lights were turned off, the slow-phase velocity of the spontaneous nystagmus slowly increased to a steady-state level within 70-120 s. 4. Horizontal smooth pursuit eye movements to a 1 degree target light moving in front of the animal +/- 20 degrees to either side of center of gaze at constant speeds were normal. Target speeds ranging from 15 to 60 degrees/s for both monocular and binocular viewing conditions were used. Binocular and monocular optokinetic nystagmus (OKN) to a full-field drum rotating at a constant velocity (5-90 degrees/s) were also normal. The initial pursuit and steady-state components of OKN were measured, as well as the velocity-storage component (optokinetic after nystagmus, OKAN).(ABSTRACT TRUNCATED AT 250 WORDS)

The amiodarone-induced optic neuropathy seldom occurs and so far, only 17 cases have been reported. These results are summarized here and the differences between them and the ischemic optic neuropathy are pointed out. We report on a 62-years-old patient who, when treated with amiodarone, developed an optic atrophy with slightly decreased visual acuity and severe visual field defects of the left eye. On the right eye we discovered shortly after discontinuing the amiodarone therapy, how, a mild swelling of the optic disc changed to an optic atrophy with analogous, irreversible changes of visual acuity and visual fields.

Measurements of binocular depth inversion using a stereoscopic slide projection with polarized light were performed in healthy volunteers before and after cannabis intake. Since binocular depth inversion represents an illusion occurring in the perception of semantically meaningful objects projected in a 3-D inverted fashion, the hypothesis can be tested that cannabis-induced "psychedelic states" represent a condition in which the human CNS is unable to correct implausible perceptual hypotheses. The data demonstrate a strong cannabis-induced impairment of binocular depth inversion.

This study was designed to provide information regarding two aspects of contrast sensitivity testing of aviator candidates: first to determine whether contrast sensitivity functions (CSF's) obtained with the Vistech Visual Contrast Test System (VCTS) are affected by cycloplegia and second to determine whether the VCTS provides useful CSF's under clinical screening conditions in a timely and simple manner. Contrast sensitivity thresholds were obtained at 5 spatial frequencies from 106 aviator candidates before and after administering a cycloplegic. CSF's obtained under cycloplegia were reduced by about 20%. The VCTS provided useful CSF's under military screening conditions, and added about 6 min to the time required for the standard flight physical.

In the South African clawed-toed frog Xenopus laevis, visual experience plays a crucial role in the formation of matching binocular maps in the tectum. The ipsilateral eye's projection, relayed through the crossed isthmotectal projection, displays marked plasticity in response to altered visual input during a critical period of development. This plasticity and the events responsible for the end of the critical period are mediated by N-methyl-D-aspartate (NMDA) receptor function. We have previously reported that chronic blockade of tectal NMDA receptors with the NMDA antagonist 5-amino-phosphonovaleric acid (APV) prevents plasticity of the crossed isthmotectal projection during the critical period, while chronic treatment with NMDA restores this plasticity after the end of the critical period. These results raise the question of whether the effects on plasticity are due to changes in electrical responsiveness of the treated tissue. In this study, we have quantitatively assessed the actions of APV and NMDA on certain aspects of tectal cell activity in Xenopus during and after the critical period by recording the output of the nucleus isthmi cells that are activated by the tectum after three weeks of treatment. We have found that chronic APV treatment does not alter tectal output, as indicated by the firing of isthmotectal axons, during the critical period and that chronic NMDA treatment increases tectal output in postcritical period Xenopus. Tectal output does not differ between normal Xenopus during and after the end of the critical period.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinotopy and binocular responsiveness were studied extracellularly in a total of 278, 61, 110 and 275 cells sampled in areas 17, 18, 19 and Clare-Bishop (CB) of Siamese cats. The misalignment of the visual axes of the two eyes was determined by the pupil reflex method in the behaving animal. The recording sessions were conducted under N2O anesthesia, supplemented with continuous infusion of short-lasting anesthetics (Saffan, Glaxo) and muscle relaxants (Gallamine triethiodide) using two types of visual stimulators presenting two-dimensional (2D) motion stimuli and the visual cues for three-dimensional (3D) motion. All of the nine Siamese cats demonstrated Boston type retinotopic abnormalities in all of cortical areas 17-19 and CB. Very few binocular cells were present in areas 17-19 and the posterior (A1-P2) CB but they were numerous in most of CB (A9-4). A significant fraction (36/78) of binocular cells in the major CB of the Siamese cats demonstrated similar response selectivity to that reported in normal CB cortex for stimulation with the 3D motion cues under both null disparity and strabismic conditions (binocular receptive fields for two eyes were optically superposed or separated by the strabismic angles estimated in the individual animals). These findings indicate that the binocular signals converging to the CB cells through different pathways (signals coming from the contralateral eye via the ipsilateral hemisphere including the interlaminar nucleus and areas 17-19, and commissural signals from the ipsilateral eye via the contralateral areas 17-19 and CB) were integrated to yield useful information for the recognition of 3D motion, and that the major CB is an actual site of binocular integration at least in Siamese cats, rather than being merely a reflection of the information processing before the CB cortex.

Visual input during a critical period of development plays a major role in the establishment of orderly connections in the developing visual system. In Xenopus laevis, the matching of visual maps from the two eyes to the optic tectum depends on binocular visual input during the critical period, which extends from late tadpole to early juvenile stages. Alterations in eye position, which produce a mismatch of the tectal maps, normally evoke a compensatory adjustment in the map of the ipsilateral eye only during the critical period. However, continuous application of the glutamate receptor agonist N-methyl-D-aspartate (NMDA) after the normal end of the critical period restores this ability to realign the visual map.

A case report of convergence insufficiency related to the use of methyldopa is presented. Methyldopa is a systemic antihypertensive agent. It has sympatholytic properties which lower blood pressure by decreasing peripheral vascular resistance. The proposed effects of methyldopa on binocular vision are reduced accommodative convergence and increased demand on fusional convergence. These effects would create a susceptibility to convergence insufficiency. To my knowledge, an association between methyldopa and convergence insufficiency has not been previously reported.