Perceptual plasticity in damaged adult visual systems

AbstractPlasticity appears to be a ubiquitous property of nervous systems, regardless of developmental stage or complexity. In the visual system of higher mammals, perceptual plasticity has been intensively studied, both during development and in adulthood. However, the last few years have seen some significant controversies arise about the existence and properties of visual plasticity after permanent damage to the adult visual system. The study of perceptual plasticity in damaged, adult visual systems is of interest for several reasons. First, it is an important means of unmasking the relative contribution of individual visual areas to visual learning, adaptation and priming, among other plastic phenomena. Second, it can provide knowledge that is essential for the development of effective therapies to rehabilitate the increasing number of people who suffer the functional consequences of damage at different levels of their visual hierarchy. This review summarizes the available evidence on the subject and proposes that visual plasticity may be just as ubiquitous after damage as it is in the intact visual system. However, damage may alter visual plasticity in ways that are still being defined

Differential impact of partial cortical blindness on gaze strategies when sitting and walking – An immersive virtual reality study

AbstractThe present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ∼80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls – with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ∼90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life

Topical rosiglitazone is an effective anti-scarring agent in the cornea

Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas

Differences in the TGF-␤1-Induced Profibrotic Response of Anterior and Posterior Corneal Keratocytes In Vitro

PURPOSE. To characterize phenotypic differences between anterior and posterior corneal keratocytes after stimulation with the profibrotic agent transforming growth factor-beta1 (TGF-␤1) in vitro. METHODS. Sixteen corneas from healthy felines were obtained immediately after death. Lamellar dissection was performed to separate the anterior and posterior stroma at approximately 50% depth either manually (n ϭ 2) or with a Moria microkeratome (300-m head; n ϭ 14). Cells from the anterior and posterior stroma were cultured separately but under identical conditions. Using immunohistochemistry and Western blot techniques, Ki-67 staining and relative expression of Thy-1, alpha smooth muscle actin (␣-SMA), and fibronectin were assessed after stimulation with different TGF-␤1 concentrations. In addition, anterior and posterior cells cultured in different concentrations of TGF-␤1 were wounded with a razor blade, and the wound area and time to closure were determined. RESULTS. Stimulation by all concentrations of TGF-␤1 increased the proportion of Ki-67-positive cells in anterior and posterior cell cultures, but this increase was noted earlier in posterior cells than in anterior cells. Increasing TGF-␤1 concentration also increased the relative expression of Thy-1, ␣-SMA, and fibronectin in anterior and posterior fibroblasts. However, anterior cells expressed these fibrotic markers at lower TGF-␤1 concentrations than did posterior keratocytes. After mechanical wounding, posterior cells closed the wound area faster than did anterior cells at all concentrations of TGF-␤1. CONCLUSIONS. The present experiments show that anterior and posterior corneal keratocytes exhibit different sensitivities to the profibrotic growth factor TGF-␤1. This heterogeneity of keratocyte response may impact wound closure after mechanical wounding. (Invest Ophthalmol Vis Sci

Enhancing visual motion discrimination by desynchronizing bifocal oscillatory activity

Visual motion discrimination involves reciprocal interactions in the alpha band between the primary visual cortex (V1) and mediotemporal areas (V5/MT). We investigated whether modulating alpha phase synchronization using individualized multisite transcranial alternating current stimulation (tACS) over V5 and V1 regions would improve motion discrimination. We tested 3 groups of healthy subjects with the following conditions: (1) individualized In-Phase V1alpha-V5alpha tACS (0° lag), (2) individualized Anti-Phase V1alpha-V5alpha tACS (180° lag) and (3) sham tACS. Motion discrimination and EEG activity were recorded before, during and after tACS. Performance significantly improved in the Anti-Phase group compared to the In-Phase group 10 and 30Â min after stimulation. This result was explained by decreases in bottom-up alpha-V1 gamma-V5 phase-amplitude coupling. One possible explanation of these results is that Anti-Phase V1alpha-V5alpha tACS might impose an optimal phase lag between stimulation sites due to the inherent speed of wave propagation, hereby supporting optimized neuronal communication

GABA and glutamate in hMT+ link to individual differences in residual visual function after occipital stroke

BACKGROUND: Damage to the primary visual cortex following an occipital stroke causes loss of conscious vision in the contralateral hemifield. Yet, some patients retain the ability to detect moving visual stimuli within their blind field. The present study asked whether such individual differences in blind field perception following loss of primary visual cortex could be explained by the concentration of neurotransmitters γ-aminobutyric acid (GABA) and glutamate or activity of the visual motion processing, human middle temporal complex (hMT+). METHODS: We used magnetic resonance imaging in 19 patients with chronic occipital stroke to measure the concentration of neurotransmitters GABA and glutamate (proton magnetic resonance spectroscopy) and functional activity in hMT+ (functional magnetic resonance imaging). We also tested each participant on a 2-interval forced choice detection task using high-contrast, moving Gabor patches. We then measured and assessed the strength of relationships between participants’ residual vision in their blind field and in vivo neurotransmitter concentrations, as well as visually evoked functional magnetic resonance imaging activity in their hMT+. Levels of GABA and glutamate were also measured in a sensorimotor region, which served as a control. RESULTS: Magnetic resonance spectroscopy-derived GABA and glutamate concentrations in hMT+ (but not sensorimotor cortex) strongly predicted blind-field visual detection abilities. Performance was inversely related to levels of both inhibitory and excitatory neurotransmitters in hMT+ but, surprisingly, did not correlate with visually evoked blood oxygenation level–dependent signal change in this motion-sensitive region. CONCLUSIONS: Levels of GABA and glutamate in hMT+ appear to provide superior information about motion detection capabilities inside perimetrically defined blind fields compared to blood oxygenation level–dependent signal changes—in essence, serving as biomarkers for the quality of residual visual processing in the blind-field. Whether they also reflect a potential for successful rehabilitation of visual function remains to be determined

Plasticity of Visual Perception After Permanent Damage to the Adult Visual Cortex

In highly visual mammals such as primates and carnivores, most of the visual information destined for conscious perception is sent from the eye, through the dorsal lateral geniculate nucleus (dLGN) of the thalamus to primary visual cortex or V1. From there, visual information is then distributed among and processed by a large number of extrastriate visual cortical areas1. Over the years, many studies have shown that damage to different visual cortical areas cause different visual deficits.curriculum_fellow; GVSliaisonwithalowvisionservice; GVScounselingofthevisuallyimparedpatien

How scars shape the neural landscape: Key molecular mediators of TGF-β1's anti-neuritogenic effects.

Following injury to the peripheral and central nervous systems, tissue levels of transforming growth factor (TGF)-β1 often increase, which is key for wound healing and scarring. However, active wound regions and scars appear to inhibit process outgrowth by regenerating neurons. We recently showed that corneal wound myofibroblasts block corneal nerve regeneration in vivo, and sensory neurite outgrowth in vitro in a manner that relies critically on TGF-β1. In turn, delayed, abnormal re-innervation contributes to long-term sensory dysfunctions of the ocular surface. Here, we exposed morphologically and biochemically-differentiated sensory neurons from the ND7/23 cell line to TGF-β1 to identify the intracellular signals regulating these anti-neuritogenic effects, contrasting them with those of Semaphorin(Sema)3A, a known inhibitor of neurite outgrowth. Neuronal morphology was quantified using phase-contrast imaging. Western blotting and specific inhibitors were then used to identify key molecular mediators. Differentiated ND7/23 cells expressed neuron-specific markers, including those involved in neurite extension and polarization. TGF-β1 increased phosphorylation of collapsin response mediator protein-2 (CRMP2), a molecule that is key for neurite extension. We now show that both glycogen synthase kinase (GSK)-3β and Smad3 modulate phosphorylation of CRMP2 after treatment with TGF-β1. GSK-3β appeared to exert a particularly strong effect, which could be explained by its ability to phosphorylate not only CRMP2, but also Smad3. In conclusion, TGF-β1's inhibition of neurite outgrowth in sensory neurons appears to be regulated through a highly-conserved signaling pathway, which involves the GSK-3β/CRMP-2 loop via both canonical and non-canonical mechanisms. It is hoped that by defining the signaling pathways that control neurite outgrowth in wound environments, it will become possible to identify optimal molecular targets to promote re-innervation following injury

Retinotopic Organization and Properties of Perceptual Learning in Cortically Blind Fields

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Neuroscience Graduate Program, 2013.Damage to the primary visual cortex (V1) or its immediate afferents results in a dense scotoma, termed cortical blindness (CB). CB subjects usually have some residual visual ability, termed blindsight, which allows them to process stimuli with high temporal and low spatial frequency content. Blindsight could be mediated either by spared V1 or extra-geniculo-calcarine input to extra-striate visual areas, especially the motion sensitive area MT+. However, how V1 damage affects the retinotopic organization of extra-striate areas is not well understood. Thus, we first characterized retinotopic organization in the lesioned hemisphere and found that CB subjects fell into two categories: (1) complete and well organized; 2) a partial map comprised only of dorsal visual areas. Sparing in the central 5 degrees of vision was associated with complete retinotopic maps. The preservation of retinotopic organization in a range of extra-striate visual areas, rather than just in MT+, implies that relearning could generalize beyond blindsight. This is relevant given the success of perceptual learning techniques in shifting the blind field border by repeated stimulation with visual motion or flickering stimuli. Work from our lab has demonstrated that global direction discriminations can be relearned in the blind field and generalize to other, untrained motion stimuli. In conjunction with our finding of preserved retinotopy, this led us to ask: (1) can visual motion relearning generalize to static, nonflickering stimuli that would not typically elicit blindsight? (2) can visual relearning be elicited de novo in CB fields by a static, non-flickering orientation discrimination task? We find the answer to be yes in both cases. Contrast sensitivity functions at the trained locations, though poorer than in the good field, showed a broad bandwidth of improvement across spatial and temporal frequencies, regardless of the training stimulus used. Relearning also generalized to untrained orientation and direction stimuli. Interestingly, subjects who trained only on orientation discrimination generalized less to untrained motion stimuli, suggesting that visual motion may be superior as a training stimulus. Our results suggest that the cortically blind visual system is able to relearn to process a much wider range of stimuli than predicted by blindsight alone