Spared perilesional V1 activity underlies training-induced recovery of luminance detection sensitivity in cortically-blind patients.

Damage to the primary visual cortex (V1) causes homonymous visual-field loss long considered intractable. Multiple studies now show that perceptual training can restore visual functions in chronic cortically-induced blindness (CB). A popular hypothesis is that training can harness residual visual functions by recruiting intact extrageniculostriate pathways. Training may also induce plastic changes within spared regions of the damaged V1. Here, we link changes in luminance detection sensitivity with retinotopic fMRI activity before and after visual discrimination training in eleven patients with chronic, stroke-induced CB. We show that spared V1 activity representing perimetrically-blind locations prior to training predicts the amount of training-induced recovery of luminance detection sensitivity. Additionally, training results in an enlargement of population receptive fields in perilesional V1, which increases blind-field coverage and may support further recovery with subsequent training. These findings uncover fundamental changes in perilesional V1 cortex underlying training-induced restoration of conscious luminance detection sensitivity in CB.

Optic Tract Shrinkage Limits Visual Restoration After Occipital Stroke.

Background and Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral visual hemifield, initiating a process of trans-synaptic retrograde degeneration. The present study examined functional implications of this process, asking if degeneration impacted the amount of visual recovery attainable from visual restoration training in chronic patients, and if restoration training impacted optic tract (OT) shrinkage. Methods: Magnetic resonance imaging was used to measure OT volumes bilaterally in 36 patients with unilateral occipital stroke. From OT volumes, we computed laterality indices (LI), estimating the stroke-induced OT shrinkage in each case. A subset of these chronic patients (n=14, 13±6 months poststroke) underwent an average of nearly 1 year of daily visual restoration training, which repeatedly stimulated vision in their blind field. The amount of visual field recovery was quantified using Humphrey perimetry, and post training magnetic resonance imaging was used to assess the impact of training on OT shrinkage. Results: OT LI was correlated with time since stroke: it was close to 0 (no measurable OT shrinkage) in subacute participants (<6 months poststroke) while chronic participants (>6 months poststroke) exhibited LI >0, but with significant variability. Visual training did not systematically alter LI, but chronic patients with baseline LI≈0 (no OT shrinkage) exhibited greater visual field recovery than those with LI>0. Conclusions: Unilateral OT shrinkage becomes detectable with magnetic resonance imaging by ≈7 months poststroke, albeit with significant interindividual variability. Although visual restoration training did not alter the amount of degeneration already sustained, OT shrinkage appeared to serve as a biomarker of the potential for training-induced visual recovery in chronic cortically blind patients.

Functional preservation and enhanced capacity for visual restoration in subacute occipital stroke.

Stroke damage to the primary visual cortex (V1) causes a loss of vision known as hemianopia or cortically-induced blindness. While perimetric visual field improvements can occur spontaneously in the first few months post-stroke, by 6 months post-stroke, the deficit is considered chronic and permanent. Despite evidence from sensorimotor stroke showing that early injury responses heighten neuroplastic potential, to date, visual rehabilitation research has focused on patients with chronic cortically-induced blindness. Consequently, little is known about the functional properties of the post-stroke visual system in the subacute period, nor do we know if these properties can be harnessed to enhance visual recovery. Here, for the first time, we show that 'conscious' visual discrimination abilities are often preserved inside subacute, perimetrically-defined blind fields, but they disappear by ∼6 months post-stroke. Complementing this discovery, we now show that training initiated subacutely can recover global motion discrimination and integration, as well as luminance detection perimetry, just as it does in chronic cortically-induced blindness. However, subacute recovery was attained six times faster; it also generalized to deeper, untrained regions of the blind field, and to other (untrained) aspects of motion perception, preventing their degradation upon reaching the chronic period. In contrast, untrained subacutes exhibited spontaneous improvements in luminance detection perimetry, but spontaneous recovery of motion discriminations was never observed. Thus, in cortically-induced blindness, the early post-stroke period appears characterized by gradual-rather than sudden-loss of visual processing. Subacute training stops this degradation, and is far more efficient at eliciting recovery than identical training in the chronic period. Finally, spontaneous visual improvements in subacutes were restricted to luminance detection; discrimination abilities only recovered following deliberate training. Our findings suggest that after V1 damage, rather than waiting for vision to stabilize, early training interventions may be key to maximize the system's potential for recovery.

Feature-based attention potentiates recovery of fine direction discrimination in cortically blind patients.

Training chronic, cortically-blind (CB) patients on a coarse [left-right] direction discrimination and integration (CDDI) task recovers performance on this task at trained, blind field locations. However, fine direction difference (FDD) thresholds remain elevated at these locations, limiting the usefulness of recovered vision in daily life. Here, we asked if this FDD impairment can be overcome by training CB subjects with endogenous, feature-based attention (FBA) cues. Ten CB subjects were recruited and trained on CDDI and FDD with an FBA cue or FDD with a neutral cue. After completion of each training protocol, FDD thresholds were re-measured with both neutral and FBA cues at trained, blind-field locations and at corresponding, intact-field locations. In intact portions of the visual field, FDD thresholds were lower when tested with FBA than neutral cues. Training subjects in the blind field on the CDDI task improved FDD performance to the point that a threshold could be measured, but these locations remained impaired relative to the intact field. FDD training with neutral cues resulted in better blind field FDD thresholds than CDDI training, but thresholds remained impaired relative to intact field levels, regardless of testing cue condition. Importantly, training FDD in the blind field with FBA lowered FDD thresholds relative to CDDI training, and allowed the blind field to reach thresholds similar to the intact field, even when FBA trained subjects were tested with a neutral rather than FBA cue. Finally, FDD training appeared to also recover normal integration thresholds at trained, blind-field locations, providing an interesting double dissociation with respect to CDDI training. In summary, mechanisms governing FBA appear to function normally in both intact and impaired regions of the visual field following V1 damage. Our results mark the first time that FDD thresholds in CB fields have been seen to reach intact field levels of performance. Moreover, FBA can be leveraged during visual training to recover normal, fine direction discrimination and integration performance at trained, blind-field locations, potentiating visual recovery of more complex and precise aspects of motion perception in cortically-blinded fields.

Visual and Motor Recovery After "Cognitive Therapeutic Exercises" in Cortical Blindness: A Case Study.

BACKGROUND AND PURPOSE: Spontaneous visual recovery is rare after cortical blindness. While visual rehabilitation may improve performance, no visual therapy has been widely adopted, as clinical outcomes are variable and rarely translate into improvements in activities of daily living (ADLs). We explored the potential value of a novel rehabilitation approach "cognitive therapeutic exercises" for cortical blindness. CASE DESCRIPTION: The subject of this case study was 48-year-old woman with cortical blindness and tetraplegia after cardiac arrest. Prior to the intervention, she was dependent in ADLs and poorly distinguished shapes and colors after 19 months of standard visual and motor rehabilitation. Computed tomographic images soon after symptom onset demonstrated acute infarcts in both occipital cortices. INTERVENTION: The subject underwent 8 months of intensive rehabilitation with "cognitive therapeutic exercises" consisting of discrimination exercises correlating sensory and visual information. OUTCOMES: Visual fields increased; object recognition improved; it became possible to watch television; voluntary arm movements improved in accuracy and smoothness; walking improved; and ADL independence and self-reliance increased. Subtraction of neuroimaging acquired before and after rehabilitation showed that focal glucose metabolism increases bilaterally in the occipital poles. DISCUSSION: This study demonstrates feasibility of "cognitive therapeutic exercises" in an individual with cortical blindness, who experienced impressive visual and sensorimotor recovery, with marked ADL improvement, more than 2 years after ischemic cortical damage.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A173).

Visual discrimination training improves Humphrey perimetry in chronic cortically induced blindness.

OBJECTIVE: To assess if visual discrimination training improves performance on visual perimetry tests in chronic stroke patients with visual cortex involvement. METHODS: 24-2 and 10-2 Humphrey visual fields were analyzed for 17 chronic cortically blind stroke patients prior to and following visual discrimination training, as well as in 5 untrained, cortically blind controls. Trained patients practiced direction discrimination, orientation discrimination, or both, at nonoverlapping, blind field locations. All pretraining and posttraining discrimination performance and Humphrey fields were collected with online eye tracking, ensuring gaze-contingent stimulus presentation. RESULTS: Trained patients recovered ∼108 degrees2 of vision on average, while untrained patients spontaneously improved over an area of ∼16 degrees2. Improvement was not affected by patient age, time since lesion, size of initial deficit, or training type, but was proportional to the amount of training performed. Untrained patients counterbalanced their improvements with worsening of sensitivity over ∼9 degrees2 of their visual field. Worsening was minimal in trained patients. Finally, although discrimination performance improved at all trained locations, changes in Humphrey sensitivity occurred both within trained regions and beyond, extending over a larger area along the blind field border. CONCLUSIONS: In adults with chronic cortical visual impairment, the blind field border appears to have enhanced plastic potential, which can be recruited by gaze-controlled visual discrimination training to expand the visible field. Our findings underscore a critical need for future studies to measure the effects of vision restoration approaches on perimetry in larger cohorts of patients.

Relearning to See in Cortical Blindness.

The incidence of cortically induced blindness is increasing as our population ages. The major cause of cortically induced blindness is stroke affecting the primary visual cortex. While the impact of this form of vision loss is devastating to quality of life, the development of principled, effective rehabilitation strategies for this condition lags far behind those used to treat motor stroke victims. Here we summarize recent developments in the still emerging field of visual restitution therapy, and compare the relative effectiveness of different approaches. We also draw insights into the properties of recovered vision, its limitations and likely neural substrates. We hope that these insights will guide future research and bring us closer to the goal of providing much-needed rehabilitation solutions for this patient population.

Beyond blindsight: properties of visual relearning in cortically blind fields.

Damage to the primary visual cortex (V1) or its immediate afferents results in a dense scotoma, termed cortical blindness (CB). CB subjects have residual visual abilities, or blindsight, which allow them to detect and sometimes discriminate stimuli with high temporal and low spatial frequency content. Recent work showed that with training, discriminations in the blind field can become more reliable, and even reach consciousness. However, the narrow spatiotemporal bandwidth of blindsight limits its functional usefulness in everyday vision. Here, we asked whether visual training can induce recovery outside the spatiotemporal bandwidth of blindsight. Specifically, could human CB subjects learn to discriminate static, nonflickering stimuli? Can such learning transfer to untrained stimuli and tasks, and does double training with moving and static stimuli provide additional advantages relative to static training alone? We found CB subjects capable of relearning static orientation discriminations following single as well as double training. However, double training with complex, moving stimuli in a separate location was necessary to recover complex motion thresholds at locations trained with static stimuli. Subjects trained on static stimuli alone could only discriminate simple motion. Finally, both groups had approximately equivalent, incomplete recovery of fine orientation and direction discrimination thresholds, as well as contrast sensitivity. These results support two conclusions: (1) from a practical perspective, complex moving stimuli and double training may be superior training tools for inducing visual recovery in CB, and (2) the cortically blind visual system can relearn to perform a wider range of visual discriminations than predicted by blindsight alone.

Transfer effects of training-induced visual field recovery in patients with chronic stroke.

OBJECTIVE: Visual training of light detection in the transition zone between blind and healthy hemianopic visual fields leads to improvement of color and simple pattern recognition. Recently, we demonstrated that visual field enlargement (VFE) also occurs when an area just beyond the transition zone is stimulated. In the current study, we attempted to determine whether this peripheral training also causes improvement in color and shape perception and reading speed. Further, we evaluated which measure of VFE relates best to improvements in performance: the average border shift (ABS) in degrees or the estimated amount of cortical surface gain (ECSG) in millimeters, using the cortical magnification factor (CMF). METHOD: Twelve patients received 40 sessions of 1-hour restorative function training (RFT). Before and after training, we measured visual fields and reading speed. Additionally, color and shape perception in the trained visual field area was measured in 7 patients. RESULTS: VFE was found for 9 of 12 patients. Significant improvements were observed in reading speed for 8 of 12 patients and in color and shape perception for 3 of 7 patients. ECSG correlates significantly with performance; ABS does not. Our data indicate that the threshold ECSG, needed for significant changes in color and shape perception and reading speed, is about 6 mm. CONCLUSIONS: White stimulus training-induced VFE can lead to improved color and shape perception and to increased reading speed in and beyond the pretraining transition zone if ECSG is sufficiently large. The latter depends on the eccentricity of the VFE.

Effects of vision restoration training on early visual cortex in patients with cerebral blindness investigated with functional magnetic resonance imaging.

Cerebral blindness is a loss of vision as a result of postchiasmatic damage to the visual pathways. Parts of the lost visual field can be restored through training. However, the neuronal mechanisms through which training effects occur are still unclear. We therefore assessed training-induced changes in brain function in eight patients with cerebral blindness. Visual fields were measured with perimetry and retinotopic maps were acquired with functional magnetic resonance imaging (fMRI) before and after vision restoration training. We assessed differences in hemodynamic responses between sessions that represented changes in amplitudes of neural responses and changes in receptive field locations and sizes. Perimetry results showed highly varied visual field recovery with shifts of the central visual field border ranging between 1 and 7°. fMRI results showed that, although retinotopic maps were mostly stable over sessions, there was a small shift of receptive field locations toward a higher eccentricity after training in addition to increases in receptive field sizes. In patients with bilateral brain activation, these effects were stronger in the affected than in the intact hemisphere. Changes in receptive field size and location could account for limited visual field recovery (± 1°), although it could not account for the large increases in visual field size that were observed in some patients. Furthermore, the retinotopic maps strongly matched perimetry measurements before training. These results are taken to indicate that local visual field enlargements are caused by receptive field changes in early visual cortex, whereas large-scale improvement cannot be explained by this mechanism.

Rehabilitation of cortical blindness secondary to stroke.

BACKGROUND: Cortical blindness is a rare complication of posterior circulation stroke. However, its complex presentation with sensory, physical, cognitive and behavioural impairments makes it one of the most challenging. Appropriate approach from a rehabilitation standpoint was never reported. AIM: Our study aims to discuss the rehabilitation methods and outcomes of a cohort of patients with cortical blindness. METHOD: The notes of all patients with cortical blindness referred to a local NHS rehabilitation service in the last 6~years were examined. Patients' demographics, presenting symptoms, scan findings, rehabilitation programmes and outcomes were documented. RESULTS: Seven patients presented to our service, six of them were males. The mean age was 63. Patients 1, 2 and 3 had total blindness with severe cognitive and behavioural impairments, wandering and akathisia. All of them failed to respond to any rehabilitation effort and the focus was on damage limitation. Pharmacological interventions had a modest impact on behaviour and sleep pattern. The 3 patients were discharged to a nursing facility. Patients 4, 5, 6 and 7 had partial blindness with variable severity. All of them suffered from significant memory impairment. However, none suffered from any behavioural, physical or other cognitive impairment. Rehabilitation efforts on 3 patients were carried out collaboratively between brain injury occupational therapists and sensory disability officers. All patients experienced significant improvement in handicap and they all maintained community placements. CONCLUSION: This small cohort of patients suggests that the rehabilitation philosophy and outcomes of these 2 distinct groups of either total or partial cortical blindness differ significantly.

New approaches to visual rehabilitation for cortical blindness: outcomes and putative mechanisms.

Cortical blindness is a chronic loss of vision following damage to the primary visual cortex (V1) or its postchiasmal afferents. Such damage is followed by a brief period of spontaneous plasticity that rarely lasts beyond 6 months. Following this initial phase, the visual deficit is thought to be stable, intractable, and permanent. Cortically blind subjects demonstrate spontaneous oculomotor adaptations to their deficits that can be further improved by saccadic localization training. However, saccadic training does not improve visual sensitivity in the blind field. In contrast, recent studies by a number of independent groups suggest that localized, repetitive perceptual training can improve visual sensitivity in the blind field, although mechanisms underlying the observed recovery remain unclear. This review discusses the current literature on rehabilitative strategies used for cortical blindness with emphasis on the use of perceptual training methods. The putative mechanisms that underlie the resulting, training-induced visual improvements are then outlined, along with the special challenges posed to their elucidation by the great variability in the extent and sometimes nature of the V1 damage sustained in different individuals.

[Rehabilitation of lesions in the visual pathways]. / Rehabilitation bei Sehbahnschäden.

This review considers diseases of the visual pathways at different levels, their consequences for relevant everyday functions and their rehabilitation. Infrachiasmatic lesions are mostly associated with central or ring scotomas causing reading problems. The use of an eccentric fixation locus in combination with text magnification often allows the patient to maintain reading ability. Chiasmatic lesions can cause orientation disability by bitemporal hemianopia and reading problems by slide phenomena along the vertical midline. Suprachiasmatic lesions lead to homonymous visual field defects. Regarding the hemianopic orientation disorder, there are two different training approaches, which have been discussed controversially: restitution of the visual field by visual stimulation versus compensation by explorative eye movements towards the hemianopic side. Previously described positive effects of exploration training were not entirely convincing due to the lack of control groups. A new randomised and controlled study has proved the effectiveness of exploration training and showed that the patients apply the improved exploration strategy to everyday life. In the control group, which received a visual field stimulation training--a potential restitution training--neither exploration nor visual fields changed. The hemianopic reading disorder depends on the distance of the field defect from the centre, i. e., the size of the reading visual field, the side of the field defect in regard to the reading direction and the presence of spontaneous adaptive strategies, such as eccentric fixation or predictive saccades. Specific reading training can be helpful. Cerebral visual impairments with visual field defects are often associated with disorders of information processing in higher cortical areas. These complex disorders usually require an interdisciplinary rehabilitation. Specific examination methods to assess functions of everyday relevance and their use as a basis for rehabilitation measures are discussed. Visual rehabilitation can be very successful in many cases and improves the patients' quality of life. One should expect that the demand for neuro-ophthalmological rehabilitation will increase, because the survival rate after severe cerebral lesions and the general lifespan are rising.

Functional rehabilitation of partial cortical blindness?

The current doctrine regards fields of partial cortical blindness as permanent once a temporally restricted window for spontaneous recovery has passed. Accordingly, neuropsychological rehabilitation mainly applies compensatory procedures that train patients to make better use of their sighted field. The more ambitious goal of functional recovery depends on the survival of pathways that continue to transmit retinal information from the blind field. Although wide-spread antero- and retrograde degeneration follows lesions that destroy or denervate the primary visual cortex and cause partial cortical blindness, several retinofugal pathways survive in cats, monkeys, and humans. In all three species, they subserve a variety of visual functions which develop and improve with practice. Post lesion plasticity is greater when the lesion occurs early in life, but changes in behavioural performance and brain responses have also been demonstrated in late lesion subjects. Although the extent of functional improvement is variable, and the most effective approaches still need to be established across cohorts, the evidence for perceptual learning in fields of cortical blindness indicates that the visual processes mediated by the surviving parts of the visual system can be harnessed to improve functional outcome.

Rehabilitation of cortical visual impairment in children.

Cortical Visual Impairment (CVI) is a condition of bilateral visual loss due to injury of visual areas in the brain without significant eye or anterior visual pathway impairment. Perinatal hypoxic ischemic encephalopathy (HIE) and postnatal anoxia are frequent etiologies of CVI and tend to result in more extensive gray and white matter injury affecting optic radiations and visual cortex. Often these children have other significant neurological disabilities and seizures as well. This article provides an analysis of a clinical database of children with CVI evaluated between January 1996 and March 2003. The results of an intensive visual stimulation program were retrospectively examined. Criteria were set to extract a fairly homogeneous group of 21 children with CVI due to perinatal HIE or postnatal anoxia who had extensive gray and white matter injury and multiple neurological deficits; 20 of 21 (95%) had symptomatic epilepsy as well. Subjects entered the study with responses ranging from just a pupillary light reflex to rudimentary perception of outline. Each subject underwent an at-home treatment program. Twenty of 21 children (95%) manifested significant improvement after 4 to 13 months on the program. Results indicate that even in this challenging group, there may be considerable neuroplasticity in visual systems leading to reintegration and visual recovery.

Visual restoration in cortical blindness: insights from natural and TMS-induced blindsight.

Unilateral damage to visual cortex of the parietal or occipital lobe can cause the patient to be unaware of contralesional visual information due to either hemispatial neglect or hemianopia. It is now known that both neglect and hemianopia result from the disruption of a dynamic interaction between cortical visual pathways and more phylogenetically primitive visual pathways to the midbrain. We consider the therapeutic implications of these cortical-subcortical interactions in the rehabilitation of hemianopia. We start with the pheonmenon of "blindsight", in which patients with hemianopia can be shown, by implicit measures of visual detection or discrimination, to process visual information without conscious awareness. Some variants of blindsight have been postulated to recruit subcortical processes, while others may reflect compensatory optimisation of processing of spared visual cortex. Both mechanisms may offer opportunities for innovative strategies for rehabilitation of visual field defects. We relate the neural mechanisms that have been proposed to underlie blindsight to those that have been suggested to underlie the recovery of visual function after rehabilitation. It is suggested that the similarity and overlap of the neural processes supporting blindsight and recovery of visual function might provide insights for effective rehabilitation strategies for restoring visual functions.