Intranasal BDNF administration promotes visual function recovery in adult amblyopic rats.

Amblyopia is the most common cause of visual impairment in one eye, with a prevalence of 1-5% in the world population. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, due to the decline in neural plasticity past the end of the visual cortex critical period. Accordingly, no pharmacological approaches are available to rescue visual functions in adult amblyopic subjects. We report that non-invasive intranasal infusion of BDNF increased levels of this neurotrophic factor in V1 and induced a recovery of visual acuity, ocular dominance and visual depth perception in adult amblyopic rats, both in reverse-occluded animals and in those with unrestricted binocular sight. Visual recovery was long-lasting, and was prevented by pharmacological blockade of TrkB signaling in the visual cortex. These results underscore the possibility to replace invasive BDNF central administration with a safe procedure of potential interest in a number of currently still cureless central nervous system pathologies. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

Acute and short-term changes in visual function with multifocal soft contact lens wear in young adults.

PURPOSE: To characterise the effects on accommodation and binocular vision in young adults of 2 distance centre multifocal soft contact lenses (MFSCLs), differing in add power. METHODS: Twenty-four young adult myopes (18-28 years; 20 females, 4 males) had baseline visual acuity, accommodation, near phoria, fixation disparity and stereopsis data collected with single vision (SV) SCLs. The same set of measurements was repeated immediately after subjects were fitted with each of two MFSCLs (with either +1.50 or +3.00 D add), and after 2 weeks of daily wear in each case. The order of testing was randomised and a one-week washout period was allowed between the first and second MFSCL trials. RESULTS: Differences in distance and near acuities with MFSCLs compared to SVSCLs were small and clinically insignificant. Compared to responses with SVSCLs, MFSCLs increased accommodative lags with this change reaching statistical significance for the +1.50 D add lens. Furthermore, both MFSCLs induced significant shifts in near phorias in the exo direction. Finally, there were no significant differences in stereopsis and fixation disparity with MFSCLs compared to SVSCLs. CONCLUSION: Differences in acuities, accommodation accuracy and binocular posture with MFSCLs compared to SVSCLs were clinically small and mostly not significant. These results predict good tolerance of MFSCLs in young patients fitted with them for myopia control.

Improved Presbyopic Vision With Miotics.

OBJECTIVE: To evaluate the efficacy of using a parasympathomimetic drug (carbachol) with an alpha agonist (brimonidine) to create optically beneficial miosis to reduce the effect of presbyopia. METHODS: In this prospective, double-masked, randomized, placebo-controlled clinical trial, 48 naturally emmetropic and presbyopic subjects aged between 43 and 56 years with an uncorrected distance visual acuity of at least 20/20 in both eyes without additional ocular pathology were eligible for inclusion. Subjects were divided into 2 groups. The treatment group (n=30 eyes) received single dose of 2.25% carbachol plus 0.2% brimonidine eye drops. The control group (n=18 eyes) received placebo drops. Drops were given to all subjects in a masked fashion, in their nondominant eye. The minimum posttreatment follow-up was 3 months. The subjects' pupil size and both near and distance visual acuities were evaluated before and after treatment at 1, 2, 4, 8, and 10 hr, by a masked examiner at the same room illumination. RESULTS: Statistically significant improvement in near visual acuity was achieved in all subjects who received carbachol plus brimonidine drops (P<0.0001). In this masked study, all subjects liked and would use this therapy if it was available. None would use the placebo. There was no evidence of tolerance or tachyphylaxis during the study period. CONCLUSIONS: Improving the depth of focus by making the pupil smaller caused statistically significant improvement in near visual acuity in emmetropic presbyopic subjects. Carbachol plus brimonidine seem to be an acceptable and safe alternative to corrective lenses and surgical procedures.

Ilusão da máscara côncava durante a síndrome de abstinência leve do álcool / Hollow-face illusion during during mild alcohol withdrawal syndrome

A ilusão da máscara côncava caracteriza-se pela inversão visual da profundidade durante a observação do reverso de uma máscara da face humana, que é percebido como convexo. O objetivo deste trabalho foi investigar a percepção monocular da profundidade ou relevo de uma máscara côncava, sob quatro condições de iluminação distintas, em 8 indivíduos com a Síndrome de Abstinência do Álcool (SAA) leve comparativamente a 8 participantes saudáveis. As contribuições nesta área de investigação são escassas e os resultados encontrados são controversos. Além disso, resta investigar a condição monocular de observação do estímulo. A máscara côncava foi posicionada no interior deuma caixa e observada através de um visor. Não foram observadas diferenças significativas entre os indivíduos com a SAA leve e os observadores saudáveis. A maioria dos observadores realizou a inversão visual da profundidade da máscara côncava, percebendo a face ilusória convexa. Ressalta-se a supremacia dos processos cognitivos, de alta ordem (top-down), sobre os processos sensoriais, de baixa ordem (bottom-up), na ilusão da máscara côncava. A observação monocular facilitou a ilusão e não foi adequada para investigar os prejuízos no processamento cognitivo de informações visuais causados pela SAA leve

The hollow-face illusion is the visual depth inversion that happens when a hollow mask of a human face is perceived as convex. The aim of thiswork was to investigate the monocular perception of depth or relief of a hollow mask, under four distinct illumination conditions, in 8 individuals with mild alcohol withdrawal, comparing to 8healthy participants. Scientific contributions in this research area are scarce and the results are controversial. Furthermore, it remains to investigate the status of monocular observationof the stimulus. The hollow mask was placed inside of a box and observed through a viewfinder. There was not significant differences between the individuals with mild alcohol withdrawal and the healthy observers. The significant majority of the observers made the visual depth inversion,perceiving the convex illusory face. It is important to notice the dominance of the high order, cognitive process (top-down) over low ordersensorial process (bottom-up) in the hollow-face illusion. The monocular observation facilitated illusion and it was not suitable to investigate the impairments in the cognitive processing of visual information caused by mild SAA

The use of galantamine in the treatment of post-traumatic oculomotor and trochlear nerve palsy.

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.

Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy.

INTRODUCTION: Neuropsychological abnormalities in transsexual patients have been reported in comparison with subjects without gender identity disorder (GID), suggesting differences in underlying neurobiological processes. However, these results have not consistently been confirmed. Furthermore, studies on cognitive effects of cross-sex hormone therapy also yield heterogeneous results. AIM: We hypothesized that untreated transsexual patients differ from men without GID in activation pattern associated with a mental rotation task and that these differences may further increase after commencing of hormonal treatment. METHOD: The present study investigated 11 male-to-female transsexual (MFTS) patients prior to cross-sex hormone therapy and 11 MFTS patients during hormone therapy in comparison with healthy men without GID. Using functional magnetic resonance imaging at 3-Tesla, a mental rotation paradigm with proven sexual dimorphism was applied to all subjects. Data were analyzed with SPM5. MAIN OUTCOME MEASURES: Patterns of brain activation associated with a mental rotation task. RESULTS: The classical mental rotation network was activated in all three groups, but significant differences within this network were observed. Men without GID exhibited significantly greater activation of the left parietal cortex (BA 40), a key region for mental rotation processes. Both transsexual groups revealed stronger activation of temporo-occipital regions in comparison with men without GID. CONCLUSIONS: Our results confirmed previously reported deviances of brain activation patterns in transsexual men from men without GID and also corroborated these findings in a group of transsexual patients receiving cross-sex hormone therapy. The present study indicates that there are a priori differences between men and transsexual patients caused by different neurobiological processes or task-solving strategies and that these differences remain stable over the course of hormonal treatment.

Fine discrimination training alters the causal contribution of macaque area MT to depth perception.

When a new perceptual task is learned, plasticity occurs in the brain to mediate improvements in performance with training. How do these changes affect the neural substrates of previously learned tasks? We addressed this question by examining the effect of fine discrimination training on the causal contribution of area MT to coarse depth discrimination. When monkeys are trained to discriminate between two coarse absolute disparities (near versus far) embedded in noise, reversible inactivation of area MT devastates performance. In contrast, after animals are trained to discriminate fine differences in relative disparity, MT inactivation no longer impairs coarse depth discrimination. This effect does not result from changes in the disparity tuning of MT neurons, suggesting plasticity in the flow of disparity signals to decision circuitry. These findings show that the contribution of particular brain area to task performance can change dramatically as a result of learning new tasks.

Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness.

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.

Disruption of eye movements by ethanol intoxication affects perception of depth from motion parallax.

Motion parallax, the ability to recover depth from retinal motion generated by observer translation, is important for visual depth perception. Recent work indicates that the perception of depth from motion parallax relies on the slow eye movement system. It is well known that ethanol intoxication reduces the gain of this system, and this produces the horizontal gaze nystagmus that law enforcement's field sobriety test is intended to reveal. The current study demonstrates that because of its influence on the slow eye movement system, ethanol intoxication impairs the perception of depth from motion parallax. Thresholds in a motion parallax task were significantly increased by acute ethanol intoxication, whereas thresholds for an identical test relying on binocular disparity were unaffected. Perhaps a failure of motion parallax plays a role in alcohol-related driving accidents; because of the effects of alcohol on eye movements, intoxicated drivers may have inaccurate or inadequate information for judging the relative depth of obstacles from motion parallax.

Incidence of stereopsis after treatment of infantile esotropia with botulinum toxin A.

PURPOSE: The incidence of stereoscopic vision following surgery for infantile esotropia has been reported, but not from patients treated with simultaneous bimedial injection of botulinum toxin A. We previously reported other findings from 41 patients treated with botulinum toxin A before the age of 12 months. The purpose of this study was to report the incidence of stereopsis in these patients after long-term follow-up. PATIENTS AND METHODS: Data were acquired by recording the response to subjective stereoscopic testing during the postinjection follow-up period when reliable subjective responses could be obtained. At least 5 years had passed following injection, and the mean age of the patients was 8 years. RESULTS: Of the 41 patients, 11 were lost to follow-up, 10 had no stereopsis, 9 had gross stereopsis (according to Titmus fly tests), 1 had 800 seconds of stereoscopic vision, 2 had 400 seconds, 2 had 200 seconds, 1 had 60 seconds, and 5 had 40 seconds. CONCLUSIONS: In this study, two-thirds of the patients acquired stereopsis following simultaneous bimedial injection of botulinum toxin A for infantile esotropia. Stereopsis acquisition following injection of botulinum toxin A had a success rate comparable with that reported for surgically corrected infantile esotropia. Bimedial injection of botulinum toxin A accompanied by alternate patching prior to injection and diligent attention at ages ranging from 4 to 12 months is a simple and efficacious method for the management of infantile esotropia.

[Impairment of safety in navigation caused by alcohol: impact on visual function]. / Beeinträchtigung der Sicherheit im Schiffsverkehr durch Alkohol. Einfluss auf das Visuelle System.

BACKGROUND: So far in Germany, no legally binding standards for blood alcohol concentration exist that prove an impairment of navigability. The aim of our interdisciplinary project was to obtain data in order to identify critical blood alcohol limits. In this context the visual system seems to be of decisive importance. MATERIALS AND METHODS: 21 professional skippers underwent realistic navigational demands soberly and alcoholized in a sea traffic simulator. The following parameters were considered: visual acuity, stereopsis, color vision, and accommodation. RESULTS: Under the influence of alcohol (average blood alcohol concentration: 1.08 per thousand ) each skipper considered himself to be completely capable of navigating. While simulations were running, all of the skippers made nautical mistakes or underestimated dangerous situations. Severe impairment in visual acuity or binocular function were not observed. Accommodation decreased by an average of 18% ( p=0.0001). In the test of color vision skippers made more mistakes ( p=0.017) and the time needed for this test was prolonged ( p=0.004). CONCLUSIONS: Changes in visual function as well as vegetative and psychological reactions could be the cause of mistakes and alcohol should therefore be regarded as a severe risk factor for security in sea navigation.

Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man.

The role of the N-methyl-D-aspartate (NMDA) neurotransmitter system in relation to psychoses is not completely understood, but represent a challenge in neurobiological research. The psychotic states induced by NMDA antagonists such as phencyclidine and ketamine have been described as being most similar to schizophrenia and the NMDA system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, has been shown to be impaired in psychotic and psychotomimetic states in healthy and schizophrenic subjects. In this study, pictures of natural and artificial objects were presented stereoscopically to 12 healthy male volunteers and depth perception assessed using an operationalized method. The effects of the psychotomimetic S-enantiomer of the anaesthetic ketamine in two different subanaesthetic doses were compared with those of a placebo. In spite of dose dependence and grave subjective and significant objective psychopathology, no significant impairment of binocular depth perception was found with (S)-ketamine. Implications related to memory function, perceptogenesis and 'bottom-up' processing in ketamine model psychosis and schizophrenia are discussed.

Functional magnetic resonance imaging (fMRI) and effects of L-dopa on visual function in normal and amblyopic subjects.

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.

Different effects of nabilone and cannabidiol on binocular depth inversion in Man.

The physiological and pathophysiological roles of the central nervous endogenous cannabinoid system are not completely understood, but still represent a challenge in basic neurobiological, cognitive, and psychiatric research. The system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, provides a model of impaired perception during psychotic states. Using this model the effects of nabilone, a psychoactive synthetic 9-trans-ketocannabinoid, and of cannabidiol, the main natural component of herbal cannabis, and a combined application of both substances on binocular depth inversion and behavioural states were investigated in nine healthy male volunteers. The time course of the effects of both substances on binocular depth inversion was analysed after oral administration using three different groups of natural stimuli. A significant impairment of binocular depth perception was found when nabilone was administered, but combined application with cannabidiol revealed somewhat reduced effects on binocular depth inversion. The influence of psychoactive cannabinoids on this perceptual model and the role of the endogenous cannabinoid system in visual information processing are discussed.

Speed of elementary visual recognition operations in Parkinson's disease as measured by the mutual masking method.

Pairs of mutually different, spatially overlapping letters were exposed for recognition to groups of patients with Parkinson's disease (PD) and the age-matched control group. Stimulus onset asynchrony (SOA), medical treatment status (de novo vs. treated), and predominant symptoms (tremor vs. hypokinetic rigidity) were an other main variables. The highly significant main effects of SOA and health status demonstrated slowing of elementary visual recognition operations in Parkinson's disease; the results are based on the experimental method that requires neither fast manual responses nor tracking of the display events by saccadic eye movements. Significant interaction between the temporal order of stimulus exposure and health status showed that impairment due to PD was more pronounced for the first stimulus, including the de novo group. Qualitatively similar recognition functions in the binocular and dichoptic conditions showed that the typical pattern of results--prevalence of S2 over S1 at intermediate SOAs--cannot be attributed to retinal processes and should be originating from central processes. An earlier finding (Bachmann, 1994) that PD patients whose nonspecific thalamic nuclei were stimulated intracranially produced qualitatively unusual recognition functions that should have been the result of stimulation, rather than PD as such.

Reduced binocular depth inversion in patients with alcoholism.

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.

Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system.

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.

Retinal toxicity associated with cisplatin and etoposide in pediatric patients.

Cisplatin is an effective chemotherapeutic agent used in the treatment of many pediatric solid tumors. Retinal toxicity is a side effect of the drug reported in adults, but is not well described in pediatric patients. We present the cases of two children treated with cisplatin and etoposide who experienced retinal toxicity documented by visual evoked response (VER) and electroretinogram (ERG). significantly, both patients had abnormal renal function. The mechanism of visual toxicity induced by cisplatin is unknown but may result from central nervous system (CNS) accumulation of drug after repeated doses, especially with high-dose platinum (HDP) containing regimens. Because clearance of platinum is related to adequate renal-function, patients with any decrease in glomerular filtration rate (GFR) may have delayed platinum excretion. We propose that the patients at greatest risk of cisplatin-induced toxicity are those pretreated with nephrotoxic therapy or those with impairment of renal function from other causes. These patients should have prospective ophthalmologic evaluation especially when treated with HDP containing regimens.

Impaired binocular depth inversion in patients with alcohol withdrawal.

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.