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Motivated by the success of cochlear implants for deaf patients, we are now facing the goal of creating a visual neuroprosthesis designed to interface with the occipital cortex as a means through which a limited but useful sense of vision could be restored in profoundly blind patients. We review the most important challenges regarding this neuroprosthetic approach and emphasize the need for basic human psychophysical research on the best way of presenting complex stimulating patterns through multiple microelectrodes. Continued research will hopefully lead to the development of and design specifications for the first generation of a cortically based visual prosthesis system.

Summary

As a human observer moves through the world, their eyes acquire a changing sequence of images. The information from this sequence is sufficient to determine the structure of a 3-D scene, up to a scale factor determined by the distance that the eyes have moved [1, 2]. There is good evidence that the human visual system accounts for the distance the observer has walked [3, 4] and the separation of the eyes [5-8] when judging the scale, shape and distance of objects. However, using an immersive virtual reality environment we created a scene that provided consistent information about scale from both distance walked and binocular vision and yet observers failed to notice when this scene expanded or contracted. This failure led to large errors in judging the size of objects. The pattern of errors cannot be explained by assuming a visual reconstruction of the scene with an incorrect estimate of interocular separation or distance walked. Instead, it is consistent with a Bayesian model of cue integration in which the efficacy of motion and disparity cues is greater at near viewing distances. Our results imply that observers are more willing to adjust their estimate of interocular separation or distance walked than to accept that the scene has changed in size.

Neurocognitive disorders are emerging as a possible complication in patients infected with HIV. Even if asymptomatic, neurocognitive abnormalities are frequently detected using a battery of tests. This supported the creation of asymptomatic neurocognitive impairment (ANI) as a new entity. In a recent article published in BMC Infectious Diseases, Magnus Gisslén and colleagues applied a statistical approach, concluding that there is an overestimation of the actual problem. In fact, about 20% of patients are classified as neurocognitively impaired without a clear impact on daily activities. In the present commentary, we discuss the clinical implications of their findings. Although a cautious approach would indicate a stricter follow-up of patients affected by this disorder, it is premature to consider it as a proper disease. Based on a review of the data in the current literature we conclude that it is urgent to conduct more studies to estimate the overall risk of progression of the asymptomatic neurocognitive impairment. Moreover, it is important to understand whether new biomarkers or neuroimaging tools can help to identify better the most at risk population.

Please see related article: http://www.biomedcentral.com/1471-2334/11/356

Food sensitivity is a common condition presenting with various clinical syndromes including migraine, urticaria, gluten enteropathy, Crohn's disease and irritable bowel syndrome. It is a heterogeneous condition affecting different organ systems and is also aetiologically diverse with subgroups due to allergy, pharmacological reactions, enzyme deficiencies and psychological causes. Clinical acceptance of food sensitivity has been delayed by the use of dubious diagnostic techniques by a minority of practitioners and the lack of laboratory diagnostic tests, but several double blind studies have now fully validated the existence of food sensitivity syndromes. More widespread recognition of food sensitivity would be cost effective for the National Health Service.

Background

Biomedical research is changing due to the rapid accumulation of experimental data at an unprecedented scale, revealing increasing degrees of complexity of biological processes. Life Sciences are facing a transition from a descriptive to a mechanistic approach that reveals principles of cells, cellular networks, organs, and their interactions across several spatial and temporal scales. There are two conceptual traditions in biological computational-modeling. The bottom-up approach emphasizes complex intracellular molecular models and is well represented within the systems biology community. On the other hand, the physics-inspired top-down modeling strategy identifies and selects features of (presumably) essential relevance to the phenomena of interest and combines available data in models of modest complexity.

Results

The workshop, "ESF Exploratory Workshop on Computational disease Modeling", examined the challenges that computational modeling faces in contributing to the understanding and treatment of complex multi-factorial diseases. Participants at the meeting agreed on two general conclusions. First, we identified the critical importance of developing analytical tools for dealing with model and parameter uncertainty. Second, the development of predictive hierarchical models spanning several scales beyond intracellular molecular networks was identified as a major objective. This contrasts with the current focus within the systems biology community on complex molecular modeling.

Conclusion

During the workshop it became obvious that diverse scientific modeling cultures (from computational neuroscience, theory, data-driven machine-learning approaches, agent-based modeling, network modeling and stochastic-molecular simulations) would benefit from intense cross-talk on shared theoretical issues in order to make progress on clinically relevant problems.

Idiopathic scoliosis is a common deformity in the adolescent age group. It is now known to be a hereditary condition, demanding careful family scrutiny. Furthermore, studies of the natural history have proven its serious long term consequences. As spinal curvatures may progress insidiously and relentlessly, early diagnosis becomes the hallmark of management. Mass screening for spinal curvatures by family physicians and medical resource personnel is recommended as a practical approach to early definition of this problem.

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During the last decade brain transcriptome profiling by DNA microarrays has matured, developed sound experimental design standards, reporting practices, analytical procedures, and data sharing resources. It has become a powerful scientific tool in the exploratory research portfolio. Along this journey by trial and error, we encountered a number of intriguing questions and comments - pondering the value of hypothesis-driven research, appropriate sample size, the importance and interpretation of transcripts changes vis-à-vis protein changes, the role of statistical stringency, false discovery and magnitude of expression change, and many other interesting questions. Our field fully acknowledges and tries to address all of these challenges associated with high-throughput, data-driven transcriptomics. As a research field, we strongly advocate implementing the highest standards of our trade, and we deeply believe that transcriptome profiling studies will continue to be essential for deciphering the pathophysiological mechanisms leading to complex brain disorders.

Interest in alternative medicine is increasing. Family physicians, frequently asked by patients about the merits of these practices, must increase their knowledge in order to develop an enlightened, scientific approach to the subject. Homeopathy is one such system of medicine; it was founded by Dr. Samuel Hahnemann nearly 200 years ago. Clinical research in homeopathy is in the very early stages. To date, clinical trials to determine the efficacy of individual homeopathic remedies and the validity of homeopathic theory generally have been inconclusive. It is to be hoped that clinical research in homeopathy will continue so that we can increase our knowledge and provide our patients with better answers to their questions.

Background

Optic neuritis is a frequent manifestation of multiple sclerosis. Visual deficits range from a minor impairment of visual functions through to complete loss of vision. Although many patients recover almost completely, roughly 35% of patients remain visually impaired for years, and therapeutic options for those patients hardly exist. Vision restoration therapy is a software-based visual training program that has been shown to improve visual deficits after pre- and postchiasmatic injury. The aim of this pilot study is to evaluate whether residual visual deficits after past or recent optic neuritis can be reduced by means of vision restoration therapy.

Methods/design

A randomized, controlled, patient- and observer-blinded clinical pilot study (VISION study) was designed to evaluate the efficacy of vision restoration therapy in optic neuritis patients. Eighty patients with a residual visual deficit after optic neuritis (visual acuity ≤0.7 and/or scotoma) will be stratified according to the time of optic neuritis onset (manifestation more than 12 months ago (40 patients, fixed deficit) versus manifestation 2 to 6 months ago (40 patients, recent optic neuritis)), and randomized into vision restoration therapy arm or saccadic training arm (control intervention). Patients will be instructed to complete a computer-based visual training for approximately 30 minutes each day for a period of 6 months. Patients and evaluators remain blinded to the treatment allocation throughout the study. All endpoints will be analyzed and P-values < 0.05 will be considered statistically significant. The primary outcome parameter will be the expansion of the visual field after 3 and 6 months of treatment as determined by static visual field perimetry and high resolution perimetry. Secondary outcome variables will include visual acuity at both low and high contrast, glare contrast sensitivity, visually evoked potentials, optical coherence tomography and other functional tests of the visual system, alertness, health-related quality of life, fatigue, and depression.

Discussion

If vision restoration therapy is shown to improve visual function after optic neuritis, this method might be a first therapeutic option for patients with incomplete recovery from optic neuritis.

Trial registration

NCT01274702

PURPOSE

With the goal of eventually restoring functional vision in patients with retinal degenerative diseases, USC/Second Sight Medical Products, Inc. chronically implanted blind human subjects with a prototype epiretinal prosthesis consisting of a 4 × 4 array of 16 stimulating electrodes. To accurately represent a visual scene, a visual prosthesis must convey luminance information across a range of brightness levels. To achieve this, the brightness of phosphenes produced by an individual electrode should scale appropriately with luminance, and the same luminance should produce equivalently bright phosphenes across the entire electrode array. The goal was to examine how apparent brightness changes as a function of stimulation intensity across electrodes.

METHODS

As described in previous studies, electrical stimulation of intact cells of the neural retina using this prosthetic device reliably elicits visual percepts in human subjects blinded by retinitis pigmentosa. Here, apparent brightness for a range of electrical amplitudes was measured using both subjective magnitude rating and brightness-matching procedures in chronically implanted human subjects.

RESULTS

It was found that apparent brightness can be described as a power function of stimulation intensity. The same model can also predict brightness matching across electrodes.

CONCLUSIONS

These results suggest that a relatively simple model for scaling current across electrodes may be capable of producing equivalently bright phosphenes across an entire array.

Background

Topographical disorientation represents one of the main consequences of brain injury. Up to now several methodological approaches have been used in the assessment of the brain injured patient's navigational abilities showing a moderate correlation with the impairments observed in everyday contexts.

Methods

We propose a combination of standardized neuropsychological tests and a more situated virtual reality-based assessment for the evaluation of spatial orientation in brain injured patients.

Results

When tested with this virtual reality integrated procedure patients showed performance and execution times congruent with their neuropsychological evaluation. When compared to a control group, patients revealed significantly slower times and greater errors in solving virtual reality based spatial tasks.

Conclusion

The use of virtual reality, when combined with classical neuropsychological tests, can provide an effective tool for the study of topographical disorientation.

Most scene segmentation and categorization architectures for the extraction of features in images and patches make exhaustive use of 2D convolution operations for template matching, template search, and denoising. Convolutional Neural Networks (ConvNets) are one example of such architectures that can implement general-purpose bio-inspired vision systems. In standard digital computers 2D convolutions are usually expensive in terms of resource consumption and impose severe limitations for efficient real-time applications. Nevertheless, neuro-cortex inspired solutions, like dedicated Frame-Based or Frame-Free Spiking ConvNet Convolution Processors, are advancing real-time visual processing. These two approaches share the neural inspiration, but each of them solves the problem in different ways. Frame-Based ConvNets process frame by frame video information in a very robust and fast way that requires to use and share the available hardware resources (such as: multipliers, adders). Hardware resources are fixed- and time-multiplexed by fetching data in and out. Thus memory bandwidth and size is important for good performance. On the other hand, spike-based convolution processors are a frame-free alternative that is able to perform convolution of a spike-based source of visual information with very low latency, which makes ideal for very high-speed applications. However, hardware resources need to be available all the time and cannot be time-multiplexed. Thus, hardware should be modular, reconfigurable, and expansible. Hardware implementations in both VLSI custom integrated circuits (digital and analog) and FPGA have been already used to demonstrate the performance of these systems. In this paper we present a comparison study of these two neuro-inspired solutions. A brief description of both systems is presented and also discussions about their differences, pros and cons.

Background

Unilateral peripheral vestibular loss results in gait and balance impairment, dizziness and oscillopsia. Vestibular rehabilitation benefits patients but optimal treatment remains unkown. Virtual reality is an emerging tool in rehabilitation and provides opportunities to improve both outcomes and patient satisfaction with treatment. The Nintendo Wii Fit Plus® (NWFP) is a low cost virtual reality system that challenges balance and provides visual and auditory feedback. It may augment the motor learning that is required to improve balance and gait, but no trials to date have investigated efficacy.

Methods/Design

In a single (assessor) blind, two centre randomised controlled superiority trial, 80 patients with unilateral peripheral vestibular loss will be randomised to either conventional or virtual reality based (NWFP) vestibular rehabilitation for 6 weeks. The primary outcome measure is gait speed (measured with three dimensional gait analysis). Secondary outcomes include computerised posturography, dynamic visual acuity, and validated questionnaires on dizziness, confidence and anxiety/depression. Outcome will be assessed post treatment (8 weeks) and at 6 months.

Discussion

Advances in the gaming industry have allowed mass production of highly sophisticated low cost virtual reality systems that incorporate technology previously not accessible to most therapists and patients. Importantly, they are not confined to rehabilitation departments, can be used at home and provide an accurate record of adherence to exercise. The benefits of providing augmented feedback, increasing intensity of exercise and accurately measuring adherence may improve conventional vestibular rehabilitation but efficacy must first be demonstrated.

Trial registration

Clinical trials.gov identifier: NCT01442623

RPE65 is an isomerohydrolase expressed in retinal pigment epithelium. It is critical for the regeneration of the visual pigment necessary for both rod and cone-mediated vision. Mutations in human RPE65 cause Leber’s congenital amaurosis and other forms of autosomal recessive retinitis pigmentosa which are associated with early-onset blindness. Several RPE65 animal models including two different mouse models and a naturally occurring canine model have been thoroughly characterized to determine the mechanisms that underlie RPE65 associated retinal dystrophies. More recently, substantial effort has gone into designing gene therapies for these diseases. Based on several encouraging reports from animal models, at least three clinical trials are currently underway for the treatment of LCA using modified AAV vectors carrying the RPE65 cDNA and have reported positive preliminary results.

Biology today is at a crossroads. The molecular paradigm, which so successfully guided the discipline throughout most of the 20th century, is no longer a reliable guide. Its vision of biology now realized, the molecular paradigm has run its course. Biology, therefore, has a choice to make, between the comfortable path of continuing to follow molecular biology's lead or the more invigorating one of seeking a new and inspiring vision of the living world, one that addresses the major problems in biology that 20th century biology, molecular biology, could not handle and, so, avoided. The former course, though highly productive, is certain to turn biology into an engineering discipline. The latter holds the promise of making biology an even more fundamental science, one that, along with physics, probes and defines the nature of reality. This is a choice between a biology that solely does society's bidding and a biology that is society's teacher.

Objective

To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD.

Methods

Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized as an interval-scaled, latent variable of visual ability based on the near-vision subscale of the National Eye Institute Vision Function Questionnaire-25 plus Supplement.

Results

Visual ability was highly correlated with visual acuity. However, a multivariate model revealed that patient coping strategies and cognitive function contributed to their ability to perform near-vision activities independent of visual acuity.

Conclusions

Patients with AMD vary in their coping strategies and cognitive function and in their visual acuity, and that variability determines patients’ self-report of vision function. Understanding patient coping mechanisms and cognition may help increase the precision of vision rating scales and suggest new interventions to improve vision function and quality of life in patients with AMD.

Trial Registration

clinicaltrials.gov Identifier: NCT00572039

Live theater is typically designed to alter the state of mind of the audience. Indeed, the perceptual inputs issuing from a live theatrical performance are intended to represent something else, and the actions, emphasized by the writing and staging, are the key prompting the adhesion of viewers to fiction, i.e., their belief that it is real. This phenomenon raises the issue of the cognitive processes governing access to a fictional reality during live theater and of their cerebral underpinnings. To get insight into the physiological substrates of adhesion we recreated the peculiar context of watching live drama in a functional magnetic resonance imaging (fMRI) experiment, with simultaneous recording of heart activity. The instants of adhesion were defined as the co-occurrence of theatrical events determined a priori by the stage director and the spectators’ offline reports of moments when fiction acted as reality. These data served to specify, for each spectator, individual fMRI time-series, used in a random-effect group analysis to define the pattern of brain response to theatrical events. The changes in this pattern related to subjects’ adhesion to fiction, were investigated using a region of interest analysis. The results showed that adhesion to theatrical events correlated with increased activity in the left BA47 and posterior superior temporal sulcus, together with a decrease in dynamic heart rate variability, leading us to discuss the hypothesis of subtle changes in the subjects’ state of awareness, enabling them to mentally dissociate physical and mental (drama-viewing) experiences, to account for the phenomenon of adhesion to dramatic fiction.

Diabetic retinopathy progresses through three distinct stages. A rational approach to management is based on an understanding of the pathophysiology of each stage. Based on the results of national multicentered clinical trials of laser photocoagulation and other treatments, advances in our understanding of the pathogenesis and treatment can now make a dramatic impact on blindness in the diabetic population: Panretinal laser photocoagulation treatment can reduce the risk of vision loss from high-risk proliferative diabetic retinopathy by at least 50%. Laser photocoagulation treatment of clinically significant diabetic macular edema can reduce the risk of vision loss by more than 50%. Vitrectomy can restore useful vision to some patients with severe diabetic retinopathy and vitreous hemorrhage with or without an accompanying traction retinal detachment. Diabetes 2000 is a new project sponsored by the American Academy of Ophthalmology, the goal of which is to eliminate preventable blindness from diabetes by the year 2000. As its name implies, Diabetes 2000 will be a long-term project aimed at a specific disease--diabetic retinopathy and its complications. It will provide the latest research findings to ophthalmologists and primary care physicians as the first priority, followed by the education of patients and the general public. Recent advances and treatment guidelines for the medical and surgical treatment of diabetic eye disease will be emphasized through the continuing education of ophthalmologists, other physicians, and allied health professionals. In later phases, educational programs for diabetic persons and the public will be developed.(ABSTRACT TRUNCATED AT 250 WORDS)

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AIMS--There is increasing awareness of the needs of children with low vision, particularly in developing countries where programmes of integrated education are being developed. However, appropriate low vision services are usually not available or affordable. The aims of this study were, firstly, to assess the need for spectacles and optical low vision devices in students with low vision in schools for the blind in Kenya and Uganda; secondly, to evaluate inexpensive locally produced low vision devices; and, finally, to evaluate simple methods of identifying those low vision students who could read N5 to N8 print after low vision assessment. METHODS--A total of 230 students were examined (51 school and 16 university students in Uganda and 163 students in Kenya, aged 5-22 years), 147 of whom had a visual acuity of less than 6/18 to perception of light in the better eye at presentation. After refraction seven of the 147 achieved 6/18 or better. Eighty two (58.6%) of the 140 students with low vision (corrected visual acuity in the better eye of less than 6/18 to light perception) had refractive errors of more than 2 dioptres in the better eye, and 38 (27.1%) had more than 2 dioptres of astigmatism. RESULTS--Forty six per cent of students with low vision (n = 64) could read N5-N8 print unaided or with spectacles, as could a further 33% (n = 46) with low vision devices. Low vision devices were indicated in a total of 50 students (35.7%). The locally manufactured devices could meet two thirds of the need. CONCLUSION--A corrected distance acuity of 1/60 or better had a sensitivity of 99.1% and a specificity of 56.7% in predicting the ability to discern N8 print or better. The ability to perform at least two of the three simple tests of functional vision had a sensitivity of 95.5% and a specificity of 63.3% in identifying the students able to discern N8 or better.

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Age-related macular disease (AMD) accounts for more than 50% of blind registration in Western society. Patients with AMD are classified as having early disease, in which visual function is well preserved, or late disease, in which central vision is lost. Until recently, there was no therapy available by which the course of the disorder could be modified. Now, the most common form of late-stage AMD — choroidal neovascularization — responds to treatment with anti-VEGF therapies; although visual loss is modified in a portion of these cases, no therapeutic approach exists that alters the evolution from early to late disease. However, as discussed in this Review, research over the last few years has demonstrated several features of AMD that are likely to be amenable to treatment. Potential targets for treatment are described, and possible therapeutic approaches are discussed.

The notion that a computer can decode brain signals to infer the intentions of a human and then enact those intentions directly through a machine is becoming a realistic technical possibility. These types of devices are known as brain-computer interfaces (BCIs). The evolution of these neuroprosthetic technologies could have significant implications for patients with motor disabilities by enhancing their ability to interact and communicate with their environment. The cortical physiology most investigated and used for device control has been brain signals from the primary motor cortex. To date, this classic motor physiology has been an effective substrate for demonstrating the potential efficacy of BCI-based control. However, emerging research now stands to further enhance our understanding of the cortical physiology underpinning human intent and provide further signals for more complex brain-derived control. In this review, the authors report the current status of BCIs and detail the emerging research trends that stand to augment clinical applications in the future.

Computer vision holds great promise for helping persons with blindness or visual impairments (VI) to interpret and explore the visual world. To this end, it is worthwhile to assess the situation critically by understanding the actual needs of the VI population and which of these needs might be addressed by computer vision. This article reviews the types of assistive technology application areas that have already been developed for VI, and the possible roles that computer vision can play in facilitating these applications. We discuss how appropriate user interfaces are designed to translate the output of computer vision algorithms into information that the user can quickly and safely act upon, and how system-level characteristics affect the overall usability of an assistive technology. Finally, we conclude by highlighting a few novel and intriguing areas of application of computer vision to assistive technology.

Background

Body change illusions have been of great interest in recent years for the understanding of how the brain represents the body. Appropriate multisensory stimulation can induce an illusion of ownership over a rubber or virtual arm, simple types of out-of-the-body experiences, and even ownership with respect to an alternate whole body. Here we use immersive virtual reality to investigate whether the illusion of a dramatic increase in belly size can be induced in males through (a) first person perspective position (b) synchronous visual-motor correlation between real and virtual arm movements, and (c) self-induced synchronous visual-tactile stimulation in the stomach area.

Methodology

Twenty two participants entered into a virtual reality (VR) delivered through a stereo head-tracked wide field-of-view head-mounted display. They saw from a first person perspective a virtual body substituting their own that had an inflated belly. For four minutes they repeatedly prodded their real belly with a rod that had a virtual counterpart that they saw in the VR. There was a synchronous condition where their prodding movements were synchronous with what they felt and saw and an asynchronous condition where this was not the case. The experiment was repeated twice for each participant in counter-balanced order. Responses were measured by questionnaire, and also a comparison of before and after self-estimates of belly size produced by direct visual manipulation of the virtual body seen from the first person perspective.

Conclusions

The results show that first person perspective of a virtual body that substitutes for the own body in virtual reality, together with synchronous multisensory stimulation can temporarily produce changes in body representation towards the larger belly size. This was demonstrated by (a) questionnaire results, (b) the difference between the self-estimated belly size, judged from a first person perspective, after and before the experimental manipulation, and (c) significant positive correlations between these two measures. We discuss this result in the general context of body ownership illusions, and suggest applications including treatment for body size distortion illnesses.

Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement.

Background

Visual loss following stroke impacts significantly on activities of daily living and is an independent risk factor for becoming dependent. Routinely, allied health clinicians provide training for visual field loss, mainly with eye movement based therapy. The effectiveness of the compensatory approach to rehabilitation remains inconclusive largely due to difficulty in validating functional outcome with the varied type and dosage of therapy received by an individual patient. This study aims to determine which treatment is more effective, a standardized approach or individualized therapy in patients with homonymous hemianopia post stroke.

Methods/Design

This study is a double-blind randomized controlled, multicenter trial. A standardised scanning rehabilitation program (Neuro Vision Technology (NVT) program) of 7 weeks at 3 times per week, is compared to individualized therapy recommended by clinicians.

Discussion

The results of the trial will provide information that could potentially inform the allocation of resources in visual rehabilitation post stroke.

Trial Registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000494033