Primary Visual Pathway Research Articles

Neuro-Ophthalmology Annual Review.

The aim of this study was to update the practicing ophthalmologist on the English-language neuro-ophthalmology literature from the prior year. This study is a review of English-language literature from August 1, 2012, to August 1, 2013. The authors searched PubMed articles published from August 1, 2012, to August 1, 2013, limited to English-language publications including original articles, review articles, and case reports and excluding letters to the editor, unpublished work, and abstracts. We researched the following topics: pupillary abnormalities, eye movement dysfunction, neuromuscular diseases, optic neuropathies, optic neuritis and demyelinating disease including multiple sclerosis, lesions of the chiasm and posterior primary visual pathways, elevated intracranial pressure, tumors and aneurysms affecting the visual pathways, vascular diseases, higher visual functions, and neuroimaging advances. We intend to share clinically relevant literature of the past year with the practicing ophthalmologist. We aimed to highlight remarkable and interesting literature rather than exhaustively including all new neuro-ophthalmological publications of the year. We reviewed literature in the past year with a focus on relevance and novelty. This review updates the comprehensive ophthalmologist on neuro-ophthalmic topics.

Nonneuronal Control of the Differential Distribution of Myelin Along Retinal Ganglion Cell Axons in the Mouse

In most mammalian species, retinal ganglion cell (RGC) axons are myelinated in the optic nerve, but remain nonmyelinated in the retinal nerve fiber layer and the most proximal (i.e., retina-near) region of the nerve. Here we analyzed whether RGCs are involved in the control of this characteristic distribution of oligodendrocytes and myelin in the primary visual pathway of mice. Neurospheres were enriched in oligodendrocyte progenitor cells (OPCs) by a short-term exposure to platelet-derived growth factor (PDGF) and grafted into the retina of young postnatal mice close to the optic disc. Immunohistochemistry was performed to study the integration and differentiation of the grafted cells, and the formation of donor-derived myelin in the normally nonmyelinated retinal nerve fiber layer and intrabulbar and most proximal retrobulbar region of the optic nerve. Intraretinal transplantations of small-sized PDGF-treated neurospheres into young postnatal mice resulted in extensive integration of the grafted cells into host retinas. A significant fraction of the donor cells differentiated into oligodendrocytes that myelinated the nerve fiber layer. Importantly, RGC axon segments within the normally nonmyelinated intrabulbar and most proximal retrobulbar region of the nerve also became myelinated in a fraction of animals. This is the first report demonstrating that the normally nonmyelinated intrabulbar and retrobulbar segments of RGC axons are competent to become myelinated. Results support the view that the differential distribution of myelin and oligodendrocytes in the primary visual pathway is controlled by nonneuronal factors rather than by the RGCs themselves.

A synaptic signature for ON- and OFF-center parasol ganglion cells of the primate retina.

In the primate retina, parasol ganglion cells contribute to the primary visual pathway via the magnocellular division of the lateral geniculate nucleus, display ON and OFF concentric receptive field structure, nonlinear spatial summation, and high achromatic temporal-contrast sensitivity. Parasol cells may be homologous to the alpha-Y cells of nonprimate mammals where evidence suggests that N-methyl-D-aspartate (NMDA) receptor-mediated synaptic excitation as well as glycinergic disinhibition play critical roles in contrast sensitivity, acting asymmetrically in OFF- but not ON-pathways. Here, light-evoked synaptic currents were recorded in the macaque monkey retina in vitro to examine the circuitry underlying parasol cell receptive field properties. Synaptic excitation in both ON and OFF types was mediated by NMDA as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors. The NMDA-mediated current-voltage relationship suggested high Mg2+ affinity such that at physiological potentials, NMDA receptors contributed ∼20% of the total excitatory conductance evoked by moderate stimulus contrasts and temporal frequencies. Postsynaptic inhibition in both ON and OFF cells was dominated by a large glycinergic "crossover" conductance, with a relatively small contribution from GABAergic feedforward inhibition. However, crossover inhibition was largely rectified, greatly diminished at low stimulus contrasts, and did not contribute, via disinhibition, to contrast sensitivity. In addition, attenuation of GABAergic and glycinergic synaptic inhibition left center-surround and Y-type receptive field structure and high temporal sensitivity fundamentally intact and clearly derived from modulation of excitatory bipolar cell output. Thus, the characteristic spatial and temporal-contrast sensitivity of the primate parasol cell arises presynaptically and is governed primarily by modulation of the large AMPA/kainate receptor-mediated excitatory conductance. Moreover, the negative feedback responsible for the receptive field surround must derive from a nonGABAergic mechanism.

Evaluation of two treatment outcome prediction models for restoration of visual fields in patients with postchiasmatic visual pathway lesions

Visual functions of patients with visual field defects after acquired brain injury affecting the primary visual pathway can be improved by means of vision restoration training. Since the extent of the restored visual field varies between patients, the prediction of treatment outcome and its visualization may help patients to decide for or against participating in therapies aimed at vision restoration. For this purpose, two treatment outcome prediction models were established based on either self-organizing maps (SOMs) or categorical regression (CR) to predict visual field change after intervention by several features that were hypothesized to be associated with vision restoration. Prediction was calculated for visual field changes recorded with High Resolution Perimetry (HRP). Both models revealed a similar predictive quality with the CR model being slightly more beneficial. Predictive quality of the SOM model improved when using only a small number of features that exhibited a higher association with treatment outcome than the remaining features, i.e. neighborhood activity and homogeneity within the surrounding 5° visual field of a given position, together with its residual function and distance to the scotoma border. Although both models serve their purpose, these were not able to outperform a primitive prediction rule that attests the importance of areas of residual vision, i.e. regions with partial visual field function, for vision restoration.

Neuro-ophthalmology Annual Review.

To provide a clinical update of the neuro-ophthalmology literature over the last twelve months. This is an annual review of current literature from August 1, 2011 to August 1, 2012. The authors conducted a one year English language neuro-ophthalmology literature search using PubMed from August 1, 2011 to August 1, 2012 using the following search terms: pupil abnormalities, eye movements, diseases of muscle and musculoskeletal junction, optic nerve disorders, optic neuritis and multiple sclerosis, chiasm and posterior primary visual pathway lesions, increased intracranial pressure and related entities, tumors (e.g., meningioma) and aneurysm affecting the visual pathways, vascular diseases, higher visual functions, advances in neuroimaging, and miscellaneous topics in neuro-ophthalmology. The authors included original articles, review articles, and case reports, which revealed the new aspects and updates in neuro-ophthalmology. Letters to the editor, unpublished work, and abstracts were not included in this annual literature review. We propose to update the practicing clinical ophthalmologist on the most clinically relevant literature from the past year. However, this review is not meant to be all-inclusive and highlights only the literature most applicable to the practicing clinical ophthalmologist. We reviewed the literature over the past year in neuro-ophthalmology of potential interest and relevance to the comprehensive ophthalmologist. This annual review provides a brief update on a number of neuroophthalmic conditions that might be of interest to the practicing clinical ophthalmologist.

Diffusion Tensor Imaging Correlates of Visual Impairment in Multiple Sclerosis and Chronic Optic Neuritis

To compare white matter (WM) injuries associated with vision loss in multiple sclerosis (MS) and optic neuritis (ON). Twenty-three patients with clinically definite relapsing-remitting MS and chronic unilateral ON and 14 neurologically healthy volunteers were monocularly tested with Sloan 100%, 2.5%, and 1.25% contrast visual acuity charts. Primary visual pathway and whole-brain WM injury were assessed with optical coherence tomography (OCT) and diffusion tensor imaging (DTI). OCT and DTI correlates of high- and low-contrast visual impairment were identified using correlation analyses. The MS patients displayed significantly reduced retinal nerve fiber layer (RNFL) thickness and altered optic nerve and radiation DTI measures compared with the controls. In the patients, 2.5% and 1.25% contrast letter acuity in the unaffected eye correlated significantly and independently with optic nerve and optic radiation DTI measures. Visual acuity in affected eyes did not correlate with optic nerve or optic radiation DTI measures, but did correlate with DTI measures in prefrontal and temporal brain regions that were shown to connect structurally to visual cortices. In unaffected eyes, visual impairment was associated with WM injury in the visual pathway. In contrast, irrecoverable visual impairment after ON was associated with injury to frontal WM, which potentially impairs the capacity for remapping visual processing.

Multiple Adaptable Mechanisms Early in the Primate Visual Pathway

We describe experiments that isolate and characterize multiple adaptable mechanisms that influence responses of orientation-selective neurons in primary visual cortex (V1) of anesthetized macaque (Macaca fascicularis). The results suggest that three adaptable stages of machinery shape neural responses in V1: a broadly tuned early stage and a spatio-temporally tuned later stage, both of which provide excitatory input, and a normalization pool that is also broadly tuned. The early stage and the normalization pool are revealed by adapting gratings that themselves fail to evoke a response from the neuron: either low temporal frequency gratings at the null orientation or gratings of any orientation drifting at high temporal frequencies. When effective, adapting stimuli that altered the sensitivity of these two mechanisms caused reductions of contrast gain and often brought about a paradoxical increase in response gain due to a relatively greater desensitization of the normalization pool. The tuned mechanism is desensitized only by stimuli well matched to a neuron's receptive field. We could thus infer desensitization of the tuned mechanism by comparing effects obtained with adapting gratings of preferred and null orientation modulated at low temporal frequencies.

Diffusion tensor imaging of the optic radiations after optic neuritis

Trans-synaptic degeneration could exacerbate neurodegeneration in multiple sclerosis (MS). We aimed to assess whether anterograde trans-synaptic degeneration could be identified in the primary visual pathway in vivo. Diffusion tensor imaging (DTI) was used to assess the optic radiations in 15 patients with previous optic nerve inflammation and 9 healthy volunteers. A probabilistic atlas of the optic radiations was created from healthy diffusion tractography data. Lengthwise profiles for DTI parameters (axial [λ(||) ], radial [λ(⟂) ] and mean diffusivity [MD], fractional anisotropy [FA] and the angle of deviation of the principal eigenvector [α]) were analyzed for patients and controls. Patients also underwent multifocal visual evoked potential (mfVEP) assessments to characterize the latency and amplitude of cortical potentials. Correlations were performed between mfVEP latency and amplitude in the left and right visual hemi-fields and DTI parameters in the contra-lateral optic radiations. Patients displayed a significant decrease in λ(||) within the body of both optic radiations, which significantly correlated with loss of mfVEP amplitude. Abnormal λ(⟂) and FA were detected bilaterally throughout the optic radiations in patients but the abnormality was not associated with amplitude reduction or latency prolongation of the mfVEP. An abnormal α value was observed in the left optic radiations of patients, and the α value in the body of the optic radiations also correlated with mfVEP amplitude loss. The assocation between bilateral DTI abnormalities within the optic radiations and loss of afferent electrical activity could indicate anterograde trans-synaptic degeneration occurs following optic neuritis.

Sleep Deprivation Amplifies Reactivity of Brain Reward Networks, Biasing the Appraisal of Positive Emotional Experiences

Appropriate interpretation of pleasurable, rewarding experiences favors decisions that enhance survival. Conversely, dysfunctional affective brain processing can lead to life-threatening risk behaviors (e.g., addiction) and emotion imbalance (e.g., mood disorders). The state of sleep deprivation continues to be associated with maladaptive emotional regulation, leading to exaggerated neural and behavioral reactivity to negative, aversive experiences. However, such detrimental consequences are paradoxically aligned with the perplexing antidepressant benefit of sleep deprivation, elevating mood in a proportion of patients with major depression. Nevertheless, it remains unknown how sleep loss alters the dynamics of brain and behavioral reactivity to rewarding, positive emotional experiences. Using functional magnetic resonance imaging (fMRI), here we demonstrate that sleep deprivation amplifies reactivity throughout human mesolimbic reward brain networks in response to pleasure-evoking stimuli. In addition, this amplified reactivity was associated with enhanced connectivity in early primary visual processing pathways and extended limbic regions, yet with a reduction in coupling with medial frontal and orbitofrontal regions. These neural changes were accompanied by a biased increase in the number of emotional stimuli judged as pleasant in the sleep-deprived group, the extent of which exclusively correlated with activity in mesolimbic regions. Together, these data support a view that sleep deprivation not only is associated with enhanced reactivity toward negative stimuli, but imposes a bidirectional nature of affective imbalance, associated with amplified reward-relevant reactivity toward pleasure-evoking stimuli also. Such findings may offer a neural foundation on which to consider interactions between sleep loss and emotional reactivity in a variety of clinical mood disorders.

Learning to see in a virtual world

Learning to see in a virtual world

Delayed early primary visual pathway development in premature infants: high density electrophysiological evidence

Delayed early primary visual pathway development in premature infants: high density electrophysiological evidence

Specialized circuits relaying primate parallel visual pathways to area MT

Specialized circuits relaying primate parallel visual pathways to area MT

Multi-scale neural texture classification using the GPU as a stream processing engine

A neural architecture for texture classification running on the Graphics Processing Unit (GPU) under a stream processing model is presented in this paper. Textural features extraction is done in three different scales, it is based on the computations that take place on the mammalian primary visual pathway and incorporates both structural and color information. Feature vectors classification is done using a fuzzy neural network which introduces pattern analysis for orientation invariant texture recognition. Performance tests are done over a varying number of textures and the entire VisTex database. The intrinsic parallelism of the neural system led us to implement the whole architecture to run on GPUs, providing a speed-up between × 16 and × 25 for classifying textures of sizes 128 × 128 and 512 × 512 px with respect to an implementation on the CPU. A comparison of classification rates obtained with other methods is included and shows the great performance of the architecture. An average classification rate of 85.2% is obtained for 167 textures of size 512 × 512 px.

Effects of electrical stimulation of the vagus nerve on the development of visual habituation in the cat

The vagus nerve participates in the control and regulation of important autonomous functions, emotional tasks, and neural activity. Electrical vagus nerve stimulation (VNS) is an approved procedure for the treatment of refractory epilepsy in humans. VNS has also been shown to improve mood complaints and cognitive function in both human patients and animals. Thus, the purpose of this study was to analyse and describe the effects of VNS on the development and establishment of sensory habituation and electrographic activity of the visual pathway in freely moving cats. Six cats had implants placed in the optic chiasm (OC), lateral geniculate body (LGB), mesencephalic reticular formation (MRF), primary visual cortex (VC) of the left hemisphere, and left vagus nerve. Immediately after surgery, all cats presented anisocoria and relaxation of the left nictitant membrane. Also showed vegetative-type responses such as myosis, licking, and swallowing during VNS. Animals were then subjected to repeated luminous stimuli at intervals of 1 and 3 s to cause habituation. The effect of VNS on the frequency and latency of the habituation episodes and the electrographic changes in the registered brain structures were analysed. Latency analysis showed that VNS delayed the first habituation episode. VNS had transitory effects on the neural activity of the primary visual pathway structures, which caused a small but measurable delay in the establishment of habituation. In conclusion, VNS interferes with the development and establishment of visual habituation, an elementary form of non-associative learning, in freely moving cats.

Deficient responses from the lateral geniculate nucleus in humans with amblyopia

Amblyopia or lazy eye is the most common cause of uniocular blindness in adults. It is caused by a disruption to normal visual development as a consequence of unmatched inputs from the two eyes in early life, arising from a turned eye (strabismus), unequal refractive error (anisometropia) or form deprivation (e.g. cataract). Animal models based on extracellular recordings in anesthetized animals suggest that the earliest site of the anomaly in the primate visual pathway is the primary visual cortex (corresponding to the striate cortex, cytoarchitectonic area 17 and area V1), which is where inputs from the two eyes are first combined in an excitatory fashion, whereas more distal and monocular processing structures such as the retina and lateral geniculate nucleus (LGN) are normal. Using high-field functional magnetic resonance imaging in a group of human adults with amblyopia, we demonstrate that functional deficits are first observable at a thalamic level, that of the LGN. Our results suggest the need to re-evaluate the current models of amblyopia that are based on the assumption of a purely cortical dysfunction, as well as the role for the LGN in visual development.

Diffusion-Tensor Neuronal Fiber Tractography and Manganese-enhanced MR Imaging of Primate Visual Pathway in the Common Marmoset: Preliminary Results

To investigate whether diffusion-tensor tractography (DTT) of neuronal fibers is useful for delineating the configuration of the neuronal fiber trajectories in the primate visual pathway, including the well-developed optic chiasm, in comparison with tract tracing at manganese-enhanced magnetic resonance (MR) imaging. The handling methods used for all the animals in this study were approved by the institutional committee for animal experiments. Diffusion-tensor MR imaging was performed in four healthy common marmosets, and in two of these animals, manganese-enhanced MR imaging tract tracing was performed by using a 7.0-T MR imaging unit. The visual pathways were quantitatively investigated in terms of the manganese distribution observed on the manganese-enhanced MR images. The images obtained with DTT and manganese-enhanced MR imaging tract tracing were qualitatively compared, and the features of the visual pathway were verified through fusion of the reconstructed images obtained by using these two modalities. DTT provided information regarding the neuroanatomic features of the marmoset visual pathway and revealed the bilateral branching patterns of the typical primate retinogeniculate pathways, although several incorrectly tracked fibers were noted. The distribution of manganese on the manganese-enhanced MR images revealed bilateral innervation of the retinal projections and depicted the layered internal structure of the lateral geniculate nuclei bilaterally, depending on the ocularity of each layer. These morphologic findings were consistent with those of previous histopathologic studies. The findings of this preliminary study raise the possibility that DTT is useful for visualizing the neuronal fiber trajectories in primate visual pathways. http://radiology.rsnajnls.org/cgi/content/full/249/3/855/DC1.

Sensitivity for reverse-phi motion

Low-level contrast information in the primary visual pathway is represented in two different channels. ON-center cells signal positive contrasts and OFF-center cells signal negative contrasts. In this study we address the question whether initial motion analysis is performed separately in these two channels, or also through combination of signals from ON and OFF cells. We quantitatively compared motion coherence detection for regular and for reverse-phi motion stimuli. In reverse-phi motion the contrast of a pattern flips during displacements. Sensitivity is therefore based on correlating positive and negative contrasts, whereas for regular motion it is based on correlating similar contrasts. We compared tuning curves for step size and temporal interval for stimuli in which motion information was limited to a single combination of step size and interval. Tuning for step size and temporal interval was highly similar for the two types of motion. Moreover, minimal coherence thresholds for both types of motion matched quantitatively, irrespective of dot density. We also measured sensitivity for so-called no-phi motion stimuli, in which the contrast of displaced dots was set to zero. Sensitivity for no-phi motion was low for stimuli containing only black or only white dots. When both dot polarities were present in the stimulus, sensitivity was absent. Thus, motion information based on separate contrasts was effectively cancelled by a component based on different contrasts. Together these results show equal efficiency in correlating dots of opposite contrast and of similar contrast, which strongly suggests efficient detection of correlations across ON and OFF channels.

Responses of the hypothalamic paraventricular neurons to light stimulation with different wavelengths in the rat

During exposure to light with different spectral compositions, the non-visual neural system in the brain gives rise to altered various physiological aspects that are not caused by the well-known primary visual pathway. This study has been designed to investigate non-visual information processing that affects the biological rhythms in humans by studying the properties of paraventricular neurons in Sprague-Dawley rats under urethane anesthesia. The responses of paraventricular nucleus neurons by stimulation with different wavelengths of light were recorded. It turned out that neural responses were most sensitive to 550 nm wavelength light. This result suggests that a non-visual system in the hypothalamus including the paraventricular nucleus responds to light stimuli to control biological rhythms or autonomic functions.

The effect of oxygen and light on the structure and function of the neonatal rat retina

The neonatal rat is born with its eyes closed and an immature visual system, that some say is equivalent to that of a human fetus at 26 weeks of gestation. From birth, the visual system of the newborn rat will gradually mature, the first manifestation of that being the opening of the eye which usually take place at postnatal day 14. Complete maturation of the retina and visual pathways is normally reached at the end of the first month of life. The neonatal rat model thus represents a unique paradigm to study the normal and abnormal maturation of the primary visual pathways that normally occurs in utero in human subjects. Our laboratory has, over the past decade, developed two animal models of postnatally induced retinopathy, namely the Oxygen-Induced Retinopathy (OIR) that share several common features with the human Retinopathy of Prematurity (ROP) and the Light-Induced Retinopathy that is viewed by some as a valid model of some forms of Retinitis Pigmentosa (RP). The following pages review what is known of the pathophysiological processes taking place and suggest possible therapeutic avenues that could be explored in order to halt the degenerative process.

Axon tracing in the adult rat optic nerve and tract after intravitreal injection of MnDPDP using a semiautomatic segmentation technique

To develop and validate an objective technique for 3D segmentation of manganese-enhanced MR images of the optic nerve/tract (ON) in adult rats to improve contrast-to-noise (CNR) calculations and use the technique to ascertain if manganese dipyridoxyl diphosphate (MnDPDP) gives sufficient Mn(2+) enhancement compared to MnCl(2) when used for functional imaging of the visual pathway. Intravitreous injection of the manganese-releasing MR contrast agent MnDPDP (30 nmol Mn(2+)) was performed to trace the ON in adult rats (n = 4). A positive control group of rats (n = 5) received a standard preparation of MnCl(2) (200 nmol Mn(2+)), while gadodiamide (1500 nmol Gd(3+)) was administered in negative control rats (n = 2). An objective technique for 3D segmentation of the enhanced ON was developed. CNR profiles along the ON were calculated by resampling the 3D image-volume in 2D planes perpendicular to the Mn(2+) enhanced ON in 0.2 mm steps, 4 mm along the segmented ON measured from the lamina cribrosa. The ON was successfully segmented and CNR calculated accurately within 2 minutes in a representative 3D MR image volume. Intravitreal MnDPDP injection resulted in significant MRI contrast enhancement of the retina and ON after 12-24 hours similar to that of MnCl(2) injection. 3D semiautomated image segmentation and the use of MnDPDP can improve in vivo axon tracing based on MRI. Mn(2+) was found to be released from MnDPDP after intravitreal injection in sufficient amounts to obtain functional tracing of the adult rat primary visual pathway.