Systematic arcminute-scale fixational offsets in patients with early visual cortex damage

Stroke damage to the primary visual cortex (V1) causes severe visual deficits, which benefit from perceptual retraining. However, whereas training with high-contrast stimuli can locally restore orientation and motion direction discrimination abilities at trained locations, it only partially restores luminance contrast sensitivity (CS). Recent work revealed that high-contrast discrimination abilities may be preserved in the blind field of some patients early after stroke. Here, we asked if CS for orientation and direction discrimination is similarly preserved inside the blind field, to what extent, and whether it could benefit from a visual training intervention. Thirteen subacute patients (<3 months post-V1 stroke) and 12 chronic patients (>6 months post-V1 stroke) were pretested and then trained to discriminate either orientation or motion direction of Gabor patches of progressively lower contrasts as their performance improved. At baseline, more subacute than chronic participants could correctly discriminate the orientation of high-contrast Gabors in their blind field, but all failed to perform this task at lower contrasts, even when 10 Hz flicker or motion direction were added. Training improved CS in a greater portion of subacute than that of chronic participants, but no one attained normal CS, even when stimuli contained flicker or motion. We conclude that, unlike the near-complete training-induced restoration of high-contrast visual discrimination abilities, V1 damage in adulthood may severely limit the residual visual system's ability to regain normal CS. Our results support the notion that CS involves different neural substrates and computations than those required for orientation and direction discrimination in V1-damaged visual systems.

The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional recruitment of existing pathways, or both. Blindsight, a condition in which subjects with complete destruction of part of striate cortex (V1) retain extensive visual capacities within the clinically blind field, is an excellent example of altered visual function. Since the main pathway to the visual cortex is destroyed, the spared or recovered visual ability must arise from either an existing alternative pathway, or the formation of a new pathway. Using diffusion-weighted MRI, we show that both controls and blindsight subject GY, whose left V1 is destroyed, show an ipsilateral pathway between LGN (lateral geniculate nucleus) and human motion area MT+/V5 (bypassing V1). However, in addition, GY shows two major features absent in controls: (i) a contralateral pathway from right LGN to left MT+/V5, (ii) a substantial cortico-cortical connection between MT+/V5 bilaterally. Both observations are consistent with previous functional MRI data from GY showing enhanced ipsilateral activation in MT+/V5. There is also evidence for a pathway in GY from left LGN to right MT+/V5, although the lesion makes its quantification difficult. This suggests that employing alternative brain regions for processing of information following cortical damage in childhood may strengthen or establish specific connections.

The present study examined whether cortical damage in rats may disrupt the integrative processes and motor control involved in the performance of a reaction time (RT) task. To investigate the nature of the deficits in the conditioned task, rats were subjected, after learning, to a coagulation of pia brain surface of varying extent, including the frontal and parietal cortical areas. They were then tested daily for over one month. The behavioural task required the rats to hold a lever down during a variable and random delay and react quickly to the onset of a visual cue by releasing the lever within a RT limit for food reinforcement. Extensive bilateral cortical lesions had no effect on spontaneous motor activity, but severely impaired RT performance. Latencies to release the lever after the cue were dramatically increased during the first postoperative sessions and gradually returned to baseline levels within 3 weeks, whereas less dramatic but long-lasting increase in premature responding (anticipatory response before the visual cue) was observed throughout the testing sessions. More restricted lesions to the frontoparietal cortex produced a similar pattern of incorrect responding with a faster recovery of delayed responses and a strong deficit in premature responding. The major effects of lesions confined to the rostral pole of the frontal cortex were observed on premature responding, however. The present results demonstrate that the impairment in movement initiation is rapidly recovered within 2-3 weeks even after extensive thermocoagulatory lesions of the frontal and parietal areas. This recovery suggests the involvement of adaptive processes developing progressively and probably reflecting the remarkable synaptic plasticity of the extrapyramidal motor output. In contrast, the long-lasting increase in premature responding, supposed to reflect some attentional deficits, may produce anatomofunctional long-term disorganization of subcortical structures such as the basal ganglia. Interestingly enough, these results show that the rat neocortex supports functions very similar to those of primates and provide a good model for studying these higher functions in operant motor procedures that require prior associative learning and appropriate motor coordination.

Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

Transorbital alternating current stimulation modifies BOLD activity in healthy subjects and in a stroke patient with hemianopia: A 7 Tesla fMRI feasibility study

A recent theory posits that ocular drifts of fixational eye movements serve to reformat the visual input of natural images, so that the power of the input image is equalized across a range of spatial frequencies. This “spectral whitening” effect is postulated to improve the processing of high-spatial-frequency information and requires normal fixational eye movements. Given that people with macular disease exhibit abnormal fixational eye movements, do they also exhibit spectral whitening? To answer this question, we computed the power spectral density of movies of natural images translated in space and time according to the fixational eye movements (thus simulating the retinal input) of a group of observers with long-standing bilateral macular disease. Just as for people with normal vision, the power of the retinal input at low spatial frequencies was lower than that based on the 1/f2 relationship, demonstrating spectral whitening. However, the amount of whitening was much less for observers with macular disease when compared with age-matched controls with normal vision. A mediation analysis showed that the eccentricity of the preferred retinal locus adopted by these observers and the characteristics of ocular drifts are important factors limiting the amount of whitening. Finally, we did not find a normal aging effect on spectral whitening. Although these findings alone cannot form a causal link between macular disease and spectral properties of eye movements, they suggest novel potential means of modifying the characteristics of fixational eye movements, which may in turn improve functional vision for people with macular disease.

Learning to better discriminate a specific visual feature (i.e., a specific orientation in a specific region of space) has been associated with plasticity in early visual areas (sensory modulation) and with improvements in the transmission of sensory information from early visual areas to downstream sensorimotor and decision regions (enhanced readout). However, in many real-world scenarios that require perceptual expertise, observers need to efficiently process numerous exemplars from a broad stimulus class as opposed to just a single stimulus feature. Some previous data suggest that perceptual learning leads to highly specific neural modulations that support the discrimination of specific trained features. However, the extent to which perceptual learning acts to improve the discriminability of a broad class of stimuli via the modulation of sensory responses in human visual cortex remains largely unknown. Here, we used functional MRI and a multivariate analysis method to reconstruct orientation-selective response profiles based on activation patterns in the early visual cortex before and after subjects learned to discriminate small offsets in a set of grating stimuli that were rendered in one of nine possible orientations. Behavioral performance improved across 10 training sessions, and there was a training-related increase in the amplitude of orientation-selective response profiles in V1, V2, and V3 when orientation was task relevant compared with when it was task irrelevant. These results suggest that generalized perceptual learning can lead to modified responses in the early visual cortex in a manner that is suitable for supporting improved discriminability of stimuli drawn from a large set of exemplars.

1. Luis H. Ospina, MD* 1. *Assistant Professor, Pediatric Ophthalmology and Neuro-ophthalmology, Ste-Justine Hospital, University de Montreal, Montreal, Quebec, Canada After completing this article, readers should be able to: 1. Recognize cortical visual impairment (CVI) as an important cause of pediatric visual loss. 2. Identify the most frequent causes of pediatric CVI and, more specifically, understand the role of hypoxia as a cause of central visual damage. 3. Describe the different patterns and implications for future vision of hypoxic central visual damage occurring in preterm compared with term babies. 4. Know the clinical signs suggestive of CVI in children. 5. Discuss the involvement of visual functions other than visual acuity (ie, cognitive visual aspects) in CVI and correlate them with the likely affected neuroanatomic substrates. 6. Explain the value of using a multidisciplinary approach in rehabilitating children who have CVI early in their development. Vision loss caused by central nervous system damage often is referred to as CVI but also may be referred to as cerebral visual impairment or neurologic visual impairment. These terms refer to the fact that the primary defect may not necessarily be limited to the striate (primary visual) cortex and may affect other areas subserving vision, such as the visual associative cortex, optic radiations, and visual attention pathways. Although it is not yet certain which of these three terms best describes the visual deficit, it is clear that use of the label cortical blindness must be abandoned. That term not only evokes negative connotations for the child and the family but is inaccurate because in almost every instance, some degree of residual vision remains, and visual improvement can occur. CVI has become the greatest cause of pediatric visual impairment in developed countries (1)(2)(3)(4)(5) and is becoming increasingly prevalent in developing nations. CVI is a problem of increasing frequency for two primary reasons. First, the progress in neonatal care has resulted in improved survival of …

Background: This study investigated cognitive-motor interference effects after a chronic stroke diagnosis. Methods: Ten stroke patients (54.7±12.3 yrs.) and seven age-matched controls (58.4±10.6 yrs.) took part in a series of cognitive-motor tasks. Under single-motor task conditions, participants moved a cursor of the robot arm along the annulus using unaffected hand ( Circle task), or performed a center-out movement in four directions ( Cross task). Under single-cognitive task conditions, participants performed the Serial 7 (S7 task) or the Controlled Oral Word Association Test (COWAT task). Under dual-task conditions, participants performed a motor task and a cognitive task simultaneously. The movement accuracy, defined as the percent of movement trajectories within the annulus per total movement trajectories, were measured on motor tasks, and the number of correct answers were recorded on cognitive tasks. Results: Results of two-sample t statistic showed that the movement accuracy of the stroke group was lower than that of the control group, in particular under single-motor conditions (Circle: stroke 84.9±11.2% vs control 93.1±5.1%, p=0.094; Cross: stroke 77.2±13.2% vs control 88.6±8.2%, p=0.062). No significant difference was found between the control and stroke groups under single-cognitive task conditions. The control group showed no significant changes in the number of correct answers and movement accuracies between single and dual tasks. On the other hand, the stroke group showed significantly decreased movement accuracy for the Cross task compared to the Circle task (p=0.006). The stroke group’s number of correct answers in the S7 task were significantly decreased when S7 was performed together with the Cross task (10.0±5.3 vs 8.1±4.5, p=0.008). Their movement accuracy was also significantly reduced under dual-task conditions (single 77.2±13.2%, dual (COWAT+Cross) 74.6±12.4, p=0.034). Conclusions: This study confirmed that cognitive-motor interference is evident for stroke patients when they performed a cognitive task and a motor task simultaneously, such that performance in one or both of the dual tasks is worse as compared to that of each single task.

To assess the relationship between the spectroscopically measured axonal damage in the normal-appearing white matter of the brainstem, the total brain T2-hyperintense lesion volume (T2LV), and disability in patients with early relapsing-remitting multiple sclerosis (RRMS). Forty-three RRMS patients and 10 sex- and age-matched healthy controls were prospectively studied for 2 years. T2-weighted magnetic resonance (MR) images and proton MR spectroscopy were acquired at the time of recruitment and at year 2. Brainstem was considered, where large tracts join together, as a suitable region to detect early axonal damage. The T2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) resonances areas were integrated with the jMRUI program, and the ratios were calculated for the sum of the volume elements represented at brainstem. The basal NAA/Cho ratio was significantly decreased in patients compared with controls. After 2-year follow-up, there was a decrease in the NAA/Cho (-9%; p = 0.002) and NAA/Cr (-13%; p = 0.001) ratios, and an increase in the T2LV (19%; p = 0.043) in multiple sclerosis patients, whereas control subjects had no significant metabolic changes. Significant NAA/Cr ratio decreases were observed in both patients, with and without relapses, whereas T2LV only increased in patients with relapses. The final Expanded Disability Status Scale (EDSS) score correlated with T2LV at baseline, but no significant correlations were found between metabolic values, T2LV change, or EDSS score over the study period. Our data reveal an early and progressive axonal damage in relapsing-remitting multiple sclerosis. Axonal loss and T2 lesion volume seem to be at least partly dissociated processes in early stages of the disease.

An interlaboratory measurement comparison, dealing with geometrical parameters of convex spherically polished optical fiber connector ferrule endfaces, was coordinated by NIST. Most measurements were optical, using interferometric microscopes; a few were mechanical, using stylus profilometers. For radius of curvature, there were small systematic offsets between some participants' data, but these were not much greater than random uncertainties. When protrusion/undercut was defined as the distance between the fiber endface and the apex of a sphere fitted to the ferrule endface, there were only slight systematic offsets between participants' data, smaller than typical random uncertainties.

Detection of glaucomatous visual field defect by nonconventional perimetry

Introduction: Children with early brain damage or dysfunction are at risk of developing cerebral visual impairment (CVI), including visual processing dysfunctions (VPD), which currently remain largely undetected until school age. Our aim was to systematically screen for possible VPD in children born very or extremely preterm from 1 to 2 years corrected age (CA) and to evaluate the effectiveness of early referral.Method: We included N = 48 children born < 30 weeks from 1 year CA. They underwent a two-step VPD screening based on (1) neurological signs indicative of visual brain damage evaluated by neonatologists and/or pediatric neurologist and (2) a functional assessment of visual orienting functions (VOF) with an eye tracking-based test. If at least one of these assessments was abnormal for their age, the children were classified as a risk of VPD and referred to undergo conventional visual diagnostics: ophthalmic exam and visual function assessment (VFA). At 2 years CA, VOF screening was repeated and neurodevelopment was assessed.Results: 18 children (38%) were classified as at risk of VPD at 1 year CA. 7 children had abnormal neurological signs, 5 children had abnormal VOF, and 6 children had both. Subsequent ophthalmic exams (N = 14) showed severe hypermetropia in 21% and strabismus in 14%. VFA (N = 10) showed abnormal visual function and behavior in only 1 child. At 2 years CA, the total group showed an increase in abnormal VOF. Whereas the children at risk showed some normalization, the group without VPD risk at 1 year CA showed deterioration of VOF. Neurodevelopmental outcome did not clearly differ between risk groups.Conclusion: Our findings show a substantial risk of VPD during visual screening (in 38%) at 1 year CA, but relatively few deficits on subsequent conventional ophthalmic exams and VFA. The data suggest that most conventional visual diagnostic methods at this young age are not related to the established VPD risks. VOF assessment should be used complimentary to these methods. The fact that at 2 years CA the number of children with a VPD risk based on abnormal VOF increased argues for more extensive and continuous screening in risk groups, at least until school age.

Greater optic nerve and visual field damage has been reported in eyes with primary open angle glaucoma that also have cilioretinal arteries compared with fellow eyes that do not have cilioretinal arteries. The cilioretinal artery may shunt blood from the posterior ciliary arterial circulation away from the optic nerve, especially in the inferior and superior optic disc, where early glaucomatous damage often occurs. To evaluate these observations, we reviewed stereoscopic disc photographs of 122 patients with primary open angle glaucoma. Twenty-one patients had unilateral cilioretinal arteries and bilateral primary open angle glaucoma with an intraocular pressure greater than 21 mm Hg at presentation and a difference of 3 mm Hg or less between the eyes. Stereoscopic disc photographs and Goldmann visual fields were evaluated in a masked fashion. In glaucomatous eyes with comparable intraocular pressures, we found no significant optic nerve or visual field differences in eyes with cilioretinal arteries compared with eyes without cilioretinal arteries.

Aim: to assess the ability of Pulsar perimetry in detecting an early glaucomatous visual field damage in comparison with Optic coherent tomography (OCT), in early glaucoma. Material: Cross-sectional case study included 1 eye from 55 consecutive subjects containing: 27 healthy subjects and 28 patients with early Primary open angle glaucoma (POAG). Only 1 eye per subject was randomly selected, if both eyes met the inclusion criteria. Methods: All the patients underwent OCT and visual field examination in addition to full ophthalmic examinations. Receiver operating characteristic curves (ROC) were studied for all parameters. The sensitivity and specificity of the differences between normal and early glaucomatous eyes, the areas under the receiver operating characteristic curves (AROC) and positive, negative likelihood ratios were evaluated for all the single parameters and selected combined parameters. Results: Individuals with early POAG had significantly higher values of FLV at GCC, MD and sLV at Pulsar perim-etry compared to healthy individuals. There were 1.84% of cases with early glaucoma FLV, whereas there were 0.5% of cases with healthy eyes. Considering Pulsar perimetry, patients with early glaucoma had higher values of MD (0,23dB) and sLV (1,97dB), compared to MD (0,23dB) and sLV (1,62dB) in healthy individuals (p&lt;0.05). The highest values of AROC had the following parametres: FLV AROC (0,648), MD AROC (0,691), sLV AROC (0,696). According to AROC we combined the best three single parameters, FLV at GCC, MD and sLV at Pulsar perimetry, using a logistical diagnostic model. The largest AROC obtained was at the value of 0.790. Conclusion: In conclusion, parameters obtained by OCT (FLV at GCC), and Pulsar perimetry (MD and sLV) were able to show the significant differences between early POAG patients and normal subjects. Combining parameters of FLV at GCC, MD and sLV at Pulsar perimetry showed higher diagnostic capability with those top three single parameters.