Orbscan Topography in Primary Open-Angle Glaucoma

Purpose: To compare anterior and posterior corneal curvatures between eyes with primary open-angle glaucoma (POAG) and healthy eyes. Methods: This is a prospective, cross-sectional, observer-masked study. A total of 138 white subjects (one eye per patient) were consecutively recruited; 69 eyes had POAG (study group), and the other 69 comprised a group of healthy control eyes matched for age and central corneal pachymetry with the study ones. Exclusion criteria included any corneal or ocular inflammatory disease, previous ocular surgery, or treatment with carbonic anhydrase inhibitors. The same masked observer performed Goldmann applanation tonometry, ultrasound pachymetry, and Orbscan II topography in all cases. Central corneal thickness, intraocular pressure, and anterior and posterior topographic elevation maps were analyzed and compared between both groups. Results: Patients with POAG had greater forward shifting of the posterior corneal surface than that in healthy control eyes (p < 0.01). Significant differences in anterior corneal elevation between controls and POAG eyes were also found (p < 0.01). Conclusions: Primary open-angle glaucoma eyes have a higher elevation of the posterior corneal surface than that in central corneal thickness–matched nonglaucomatous eyes.

Cortical Abnormalities in Adults and Adolescents with Major Depression based on Brain Scans from 20 Cohorts Worldwide in the ENIGMA Major Depressive Disorder Working Group

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Preserved obstacle avoidance during reaching in patients with left visual neglect

We asked 12 patients with left visual neglect to bisect the gap between two cylinders or to reach rapidly between them to a more distal target zone. Both tasks demanded a motor response but these responses were quite different in nature. The bisection response was a communicative act whereby the patient indicated the perceived midpoint. The reaching task carried no imperative to bisect the gap, only to maintain a safe distance from either cylinder while steering to the target zone. Optimal performance on either task could only be achieved by reference to the location of both cylinders. Our analysis focused upon the relative influence of the left and right cylinders on the lateral location of the response. In the bisection task, all neglect patients showed qualitatively the same asymmetry, with the left cylinder exerting less influence than the right. In the reaching task, the neglect group behaved like normal subjects, being influenced approximately equally by the two cylinders. This was true for all bar two of the patients, who showed clear neglect in both tasks. We conclude that the visuomotor processing underlying obstacle avoidance during reaching is preserved in most patients with left visual neglect. (C) 2004 Elsevier Ltd. All rights reserved.

Visual-auditory integration during speech imitation in autism

Children with autistic spectrum disorder (ASD) may have poor audio-visual integration, possibly reflecting dysfunctional 'mirror neuron' systems which have been hypothesised to be at the core of the condition. In the present study, a computer program, utilizing speech synthesizer software and a 'virtual' head (Baldi), delivered speech stimuli for identification in auditory, visual or bimodal conditions. Children with ASD were poorer than controls at recognizing stimuli in the unimodal conditions, but once performance on this measure was controlled for, no group difference was found in the bimodal condition. A group of participants with ASD were also trained to develop their speech-reading ability. Training improved visual accuracy and this also improved the children's ability to utilize visual information in their processing of speech. Overall results were compared to predictions from mathematical models based on integration and non-integration, and were most consistent with the integration model. We conclude that, whilst they are less accurate in recognizing stimuli in the unimodal condition, children with ASD show normal integration of visual and auditory speech stimuli. Given that training in recognition of visual speech was effective, children with ASD may benefit from multi-modal approaches in imitative therapy and language training. (C) 2004 Elsevier Ltd. All rights reserved.

Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were rested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 mu g/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggestinga primary involvement of the 5-HT1A receptor in the observed defecit. Based on physiological and pharmacological data,we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

Pyramidal cell specialization in the occipitotemporal cortex of the vervet monkey

Pyramidal cells were injected intracellularly in fixed, flat-mounted cortical slices taken from the first and fourth visual areas (VI and V4, respectively) and cytoarchitectonic areas TEO and TE of two age and gender-matched vervet monkeys and the size, branching complexity and spine density of their basal dendritic trees determined. In both animals, we found marked differences in the pyramidal cell phenotype between cortical areas. More specifically, a consistent trend for larger, more branched and more spinous pyramidal cells with progression through VI, V4, TEO and TE was observed. These findings support earlier reports of interareal specialization in pyramidal cell structure in occipitotemporal visual areas in the macaque monkey. (c) 2005 Lippincott Williams & Wilkins.

Visual feedback alters the variations in corticospinal excitability that arise from rhythmic movements of the opposite limb

Augmented visual feedback can have a profound bearing on the stability of bimanual coordination. Indeed, this has been used to render tractable the study of patterns of coordination that cannot otherwise be produced in a stable fashion. In previous investigations (Carson et al. 1999), we have shown that rhythmic movements, brought about by the contraction of muscles on one side of the body, lead to phase-locked changes in the excitability of homologous motor pathways of the opposite limb. The present study was conducted to assess whether these changes are influenced by the presence of visual feedback of the moving limb. Eight participants performed rhythmic flexion-extension movements of the left wrist to the beat of a metronome (1.5 Hz). In 50% of trials, visual feedback of wrist displacement was provided in relation to a target amplitude, defined by the mean movement amplitude generated during the immediately preceding no feedback trial. Motor potentials (MEPs) were evoked in the quiescent muscles of the right limb by magnetic stimulation of the left motor cortex. Consistent with our previous observations, MEP amplitudes were modulated during the movement cycle of the opposite limb. The extent of this modulation was, however, smaller in the presence of visual feedback of the moving limb (FCR omega(2) =0.41; ECR omega(2)=0.29) than in trials in which there was no visual feedback (FCR omega(2)=0.51; ECR omega(2)=0.48). In addition, the relationship between the level of FCR activation and the excitability of the homologous corticospinal pathway of the opposite limb was sensitive to the vision condition; the degree of correlation between the two variables was larger when there was no visual feedback of the moving limb. The results of the present study support the view that increases in the stability of bimanual coordination brought about by augmented feedback may be mediated by changes in the crossed modulation of excitability in homologous motor pathways.

Mechanisms of axon guidance in the developing nervous system

The human brain assembles an incredible network of over a billion neurons. Understanding how these connections form during development in order for the brain to function properly is a fundamental question in biology. Much of this wiring takes place during embryonic development. Neurons are generated in the ventricular zone, migrate out, and begin to differentiate. However, neurons are often born in locations some distance from the target cells with which they will ultimately form connections. To form connections, neurons project long axons tipped with a specialized sensing device called a growth cone. The growing axons interact directly with molecules within the environment through which they grow. In order to find their targets, axonal growth cones use guidance molecules that can either attract or repel them. Understanding what these guidance cues are, where they are expressed, and how the growth cone is able to transduce their signal in a directionally specific manner is essential to understanding how the functional brain is constructed. In this chapter, we review what is known about the mechanisms involved in axonal guidance. We discuss how the growth cone is able to sense and respond to its environment and how it is guided by pioneering cells and axons. As examples, we discuss current models for the development of the spinal cord, the cerebral cortex, and the visual and olfactory systems. (c) 2005, Elsevier Inc.

Classic identity negative priming involves accessing semantic representations in the left anterior temporal cortex

Classic identity negative priming (NP) refers to the finding that when an object is ignored, subsequent naming responses to it are slower than when it has not been previously ignored (Tipper, S.P., 1985. The negative priming effect: inhibitory priming by ignored objects. Q. J. Exp. Psychol. 37A, 571-590). It is unclear whether this phenomenon arises due to the involvement of abstract semantic representations that the ignored object accesses automatically. Contemporary connectionist models propose a key role for the anterior temporal cortex in the representation of abstract semantic knowledge (e.g., McClelland, J.L., Rogers, T.T., 2003. The parallel distributed processing approach to semantic cognition. Nat. Rev. Neurosci. 4, 310-322), suggesting that this region should be involved during performance of the classic identity NP task if it involves semantic access. Using high-field (4 T) event-related functional magnetic resonance imaging, we observed increased BOLD responses in the left anterolateral temporal cortex including the temporal pole that was directly related to the magnitude of each individual's NP effect, supporting a semantic locus. Additional signal increases were observed in the supplementary eye fields (SEF) and left inferior parietal lobule (IPL). (c) 2006 Elsevier Inc. All rights reserved.

Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma

PURPOSE. To assess the level of plasma glutathione in patients with untreated primary open-angle glaucoma. METHODS. Twenty-one patients with newly diagnosed primary open-angle glaucoma and 34 age- and gender-matched control subjects were subjected to a blood analysis to detect the level of circulating glutathione in its reduced and oxidized forms. The effect of age, gender, and systemic blood pressure on circulating glutathione levels was also analyzed. RESULTS. Age had a negative effect on the level of both reduced and total glutathione (P = 0.002, r = -0.52 and P = 0.002, r = -0.52, respectively) in control subjects but not in patients with glaucoma (P > 0.05, r = 0.27, and P > 0.05, r = 0.22, respectively). In the control group, men demonstrated higher levels of both reduced and total glutathione than did women (P = 0.024 and P = 0.032, respectively). After correction for age and gender influences on blood glutathione levels, patients with glaucoma exhibited significantly lower levels of reduced and total glutathione than did control subjects (P = 0.010, F = 7.24 and P = 0.006, F = 8.38, respectively). No differences between study groups were observed in either oxidized glutathione levels or redox index (P > 0.05, F = 0.50; and P > 0.05, F = 0.30, respectively). CONCLUSIONS. Patients with glaucoma exhibit low levels of circulating glutathione, suggesting a general compromise of the antioxidative defense. Copyright © Association for Research in Vision and Ophthalmology.

Spatio-temporal imaging of corticaldesynchronization in migraine visual aura:a magnetoencephalography case study

Objective.-To determine cortical oscillatory changes involved in migraine visual aura using magnetoencephalography (MEG). Background.-Visual aura in the form of scintillating scotoma precedes migraine in many cases. The involvement of cortical spreading depression within striate and extra-striate cortical areas is implicated in the generation of the disturbance, but the details of its progression, the effects on cortical oscillations, and the mechanisms of aura generation are unclear. Methods.-We used MEG to directly image changes in cortical oscillatory power during an episode of scintillating scotoma in a patient who experiences aura without subsequent migraine headache. Using the synthetic aperture magnetometry method of MEG source imaging, focal changes in cortical oscillatory power were observed over a 20-minute period and visualized in coregistration with the patient's magnetic resonance image. Results.-Alpha band desynchronization in both the left extra-striate and temporal cortex persisted for the duration of reported visual disturbance, terminating abruptly upon disappearance of scintillations. Gamma frequency desynchronization in the left temporal lobe continued for 8 to 10 minutes following the reported end of aura. Conclusions.-Observations implicate the extra-striate and temporal cortex in migraine visual aura and suggest involvement of alpha desynchronization in generation of phosphenes and gamma desynchronization in sustained inhibition of visual function.

Transcranial magnetic stimulation to right parietal cortex modifies the attentional blink

The 'attentional blink' (AB) reflects a limitation in the ability to identify multiple items in a stream of rapidly presented information. Repetitive transcranial magnetic stimulation (rTMS), applied to a site over the right posterior parietal cortex, reduced the magnitude of the AB to visual stimuli, whilst no effect of rTMS was found when stimulation took place at a control site. The data confirm that the posterior parietal cortex may play a critical role in temporal as well as spatial aspects of visual attention.

The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

Magnocellular mediated visual-spatial attention and reading ability

This study explores the relationship between attentional processing mediated by visual magnocellular (MC) processing and reading ability. Reading ability in a group of primary school children was compared to performance on a visual cued coherent motion detection task. The results showed that a brief spatial cue was more effective in drawing attention either away or towards a visual target in the group of readers ranked in the upper 25% of the sample compared to lower ranked readers. Regression analysis showed a significant relationship between attentional processing and reading when the effects of age and intellectual ability were removed. Results suggested a stronger relationship between visual attentional and non-word reading compared to irregular word reading. (C) 2004 Lippincott Williams & Wilkins, Inc.