Residual Visual Capacities Research Articles

PC024 / #1011 DEEP LEARNING OF BRAIN SPACETIME TO PREDICT OUTCOME OF VISION RESTORATION THERAPY USING NON-INVASIVE BRAIN STIMULATION: TRACK 3: RESTORATIVE THERAPIES / NONINVASIVE STIMULATION / NEUROSTIMULATION FOR HEAD AND FACE PAIN

Vision loss following optic nerve damage does not only impair visual field function in patients, but it also alter Brain Spacetime, i.e. the dynamics of functional brain connectivity networks that support cognitive processing. As we showed repeatedly, non-invasive transcranial alternating current stimulation (tACS) can enhance residual visual capacity of the brain, opening a new window of opportunity by way of plasticity of the brain. However, treatment efficacy varies considerably between subjects and the treatment outcomes remains unpredictable.

How to test blindsight without light scatter artefacts?

light scatter artefacts are a methodological problem in testing residual visual capacities (RVCs), for instance blindsight, in patients with homonymous visual field defects (HVFDs). The term light scatter artefact describes the phenomenon that light from targets directed towards the HVFD can stray into the sighted visual field. This might enable an observer to respond correctly to information directed at her blind field despite the fact that she is unable to process that information in the blind field itself. In this manuscript, we present a review of the relevance of light scatter in visual neuroscience, discuss factors that influence the impact of light scatter and evaluate means to test for light scatter artefacts. Furthermore, we present findings from an empirical study that was aimed at developing tests for RVCs that are free of light scatter artefacts. Previous studies on light scatter only used small sample sizes and equipment that is no longer in use. Hence, their results cannot be generalized to future experiments making it necessary to run laborious light scatter tests for every new study on RVCs. To avoid this, we hereby start a pool of stimuli and paradigms which demonstrably do not elicit light scatter artefacts. To this end, we investigated 21 healthy young participants in three frequently used RVC-paradigms: (1) temporal 2AFC task, (2) movement direction discrimination, and (3) redundant target paradigm. For each paradigm, we applied the blind-spot method. But first, we had to establish that our testing paradigm was sufficiently sensitive to detect light scatter artefacts. For this, we used conditions that are known to produce strong light scatter and a paradigm that is very sensitive to such effects. Specifically, we presented white targets on a black background in a dark room. The stimuli were presented to observers’ blind spot. To check for light scatter artefacts, we used a target-detection task in a temporal 2AFC format. We obtained clear light scatter artefacts. Participants produced reliably above-chance detection performance under these conditions. The other two luminance conditions, measured in an illuminated room, did not produce light scatter artefacts. Accuracy in the temporal 2AFC task was at chance level for white targets on a grey background at the blind-spot position. Additionally, black targets on a grey background avoided light scatter artefacts in all three RVC-paradigms. In future, researchers can apply these stimulus and illumination conditions when using one of the three above paradigms in their studies. Using these conditions, they will be able to avoid light scatter artefacts without having to perform their own blind-spot tests.

Linking Multi-Modal MRI to Clinical Measures of Visual Field Loss After Stroke.

Loss of vision across large parts of the visual field is a common and devastating complication of cerebral strokes. In the clinic, this loss is quantified by measuring the sensitivity threshold across the field of vision using static perimetry. These methods rely on the ability of the patient to report the presence of lights in particular locations. While perimetry provides important information about the intactness of the visual field, the approach has some shortcomings. For example, it cannot distinguish where in the visual pathway the key processing deficit is located. In contrast, brain imaging can provide important information about anatomy, connectivity, and function of the visual pathway following stroke. In particular, functional magnetic resonance imaging (fMRI) and analysis of population receptive fields (pRF) can reveal mismatches between clinical perimetry and maps of cortical areas that still respond to visual stimuli after stroke. Here, we demonstrate how information from different brain imaging modalities—visual field maps derived from fMRI, lesion definitions from anatomical scans, and white matter tracts from diffusion weighted MRI data—provides a more complete picture of vision loss. For any given location in the visual field, the combination of anatomical and functional information can help identify whether vision loss is due to absence of gray matter tissue or likely due to white matter disconnection from other cortical areas. We present a combined imaging acquisition and visual stimulus protocol, together with a description of the analysis methodology, and apply it to datasets from four stroke survivors with homonymous field loss (two with hemianopia, two with quadrantanopia). For researchers trying to understand recovery of vision after stroke and clinicians seeking to stratify patients into different treatment pathways, this approach combines multiple, convergent sources of data to characterize the extent of the stroke damage. We show that such an approach gives a more comprehensive measure of residual visual capacity—in two particular respects: which locations in the visual field should be targeted and what kind of visual attributes are most suited for rehabilitation.

What Is New in Glaucoma: From Treatment to Biological Perspectives

Glaucoma is a chronic silent disease and an irreversible cause of blindness worldwide. Research has made many efforts to improve disease control and especially to anticipate both early diagnosis and treatment of advanced stages of glaucoma. In terms of prevention, networking between professionals and nonprofessionals is an important goal to disseminate information and help diagnose the disease early. On the other hand, the most recent approaches to treat glaucoma outcomes in its advanced stages include electrical stimulation, stem cells, exosomes, extracellular vesicles, and growth factors. Finally, neuronal plasticity-based rehabilitation methods are being studied to reeducate patients in order to stimulate their residual visual capacity. This review provides an overview of new approaches to future possible glaucoma treatment modalities and gives insight into the perspectives available nowadays in this field.

Neurochemical changes in the primate lateral geniculate nucleus following lesions of striate cortex in infancy and adulthood: implications for residual vision and blindsight.

Following lesions of the primary visual cortex (V1), the lateral geniculate nucleus (LGN) undergoes substantial cell loss due to retrograde degeneration. However, visually responsive neurons remain in the degenerated sector of LGN, and these have been implicated in mediation of residual visual capacities that remain within the affected sectors of the visual field. Using immunohistochemistry, we compared the neurochemical characteristics of LGN neurons in V1-lesioned marmoset monkeys (Callithrix jacchus) with those of non-lesioned control animals. We found that GABAergic neurons form approximately 6.5% of the neuronal population in the normal LGN, where most of these cells express the calcium-binding protein parvalbumin. Following long-term V1 lesions in adult monkeys, we observed a marked increase (~ sevenfold) in the proportion of GABA-expressing neurons in the degenerated sector of the LGN, indicating that GABAergic cells are less affected by retrograde degeneration in comparison with magno- and parvocellular projection neurons. In addition, following early postnatal V1 lesions and survival into adulthood, we found widespread expression of GABA in putative projection neurons, even outside the degenerated sectors (lesion projection zones). Our findings show that changes in the ratio of GABAergic neurons in LGN need to be taken into account in the interpretation of the mechanisms of visual abilities that survive V1 lesions in primates.

Robust Visual Responses and Normal Retinotopy in Primate Lateral Geniculate Nucleus following Long-term Lesions of Striate Cortex.

Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the LGN. In primates, these lesions also lead to scotomas, within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure. A possible contribution of LGN neurons to blindsight is predicated on two conditions: that the neurons that survive degeneration remain visually responsive, and that their receptive fields continue to represent the region of the visual field inside the scotoma. We tested these conditions in male and female marmoset monkeys (Callithrix jacchus) with partial V1 lesions at three developmental stages (early postnatal life, young adulthood, old age), followed by long recovery periods. In all cases, recordings from the degenerated LGN revealed neurons with well-formed receptive fields throughout the scotoma. The responses were consistent and robust, and followed the expected eye dominance and retinotopy observed in the normal LGN. The responses had short latencies and preceded those of neurons recorded in the extrastriate middle temporal area. These findings suggest that the pathway that links LGN neurons to the extrastriate cortex is physiologically viable and can support residual vision in animals with V1 lesions incurred at various ages.SIGNIFICANCE STATEMENT Patients with a lesion of the primary visual cortex (V1) can retain certain visually mediated behaviors, particularly if the lesion occurs early in life. This phenomenon ("blindsight") not only sheds light on the nature of consciousness, but also has implications for studies of brain circuitry, development, and plasticity. However, the pathways that mediate blindsight have been the subject of debate. Recent studies suggest that projections from the LGN might be critical, but this finding is puzzling given that the lesions causes severe cell death in the LGN. Here we demonstrate in monkeys that the surviving LGN neurons retain a remarkable level of visual function and could therefore be the source of the visual information that supports blindsight.

Facial blindsight.

Blindsight denotes unconscious residual visual capacities in the context of an inability to consciously recollect or identify visual information. It has been described for color and shape discrimination, movement or facial emotion recognition. The present study investigates a patient suffering from cortical blindness whilst maintaining select residual abilities in face detection. Our patient presented the capacity to distinguish between jumbled/normal faces, known/unknown faces or famous people’s categories although he failed to explicitly recognize or describe them. Conversely, performance was at chance level when asked to categorize non-facial stimuli. Our results provide clinical evidence for the notion that some aspects of facial processing can occur without perceptual awareness, possibly using direct tracts from the thalamus to associative visual cortex, bypassing the primary visual cortex.

Hear me Flying! Does Visual Impairment Improve Auditory Display Usability during a Simulated Flight?

Sonification refers to systems that convey information into the non-speech audio modality [1]. This technique has been largely invested in developing guidance systems for visually impaired individuals. In 2008, more than 140 systems of this type used in various application areas were referenced [2]. In aeronautics, such a system –namely the Sound Flyer– is currently used by visually impaired pilots in real flight context to control the aircraft attitude. However, it is unclear if this system would be acceptable for sighted individuals. Indeed, early visual deprivation leads to compensatory mechanisms which often result in better auditory attentional skills [7,8]. In the present study we assessed this issue. Two groups of pilots (blind vs. sighted) took part in a flight simulator experiment. They were all blindfolded to avoid potential visual information acquisition (i.e. some blind individuals had residual visual capacities). Participants had to perform successive aircraft maneuvers on the sole basis of auditory information provided by the sound flyer. Maneuvers difficulty varied with the number of parameters to apply: easy (none), medium (one: pitch or bank) or hard (two: pitch and bank). The Sound Flyer generated a pure tone (53dB SPL) modulated as a function of pitch (tonal variation) and bank (inter-aural and rhythmic variations). We assessed flight performance along with subjective (NASA-TLX) and neurological (irrelevant auditory-probe technique; [9]) measures of cognitive workload. We hypothesized that the automatic cerebral reaction to deviant auditory stimuli (10% “ti” among 90% “ta”; 56db SPL) would be affected by the difficulty [10,11] and participants’ auditory attention. Preliminary data analyses revealed that blind and sighted participants reached target-attitudes with good accuracy (mean error of 2.04°). Globally, subjective cognitive workload and brain responses to the auditory probe were influenced by the difficulty of the maneuver but not by the visual impairment. These initial results provide evidence that auditory displays are effective, not only for maintaining straight and level flight [6], but also for attaining precise aircraft attitudes. Results also suggest that flight maneuvers should remain quite simple to avoid too high cognitive workload. In other words, attitude sonification can provide robust information and, along with Brungart and Simpson [3] specifications, could contribute to the fight against spatial disorientation in the cockpit.

Blindsight in children with congenital and acquired cerebral lesions

It has been shown that unconscious visual function can survive lesions to optical radiations and/or primary visual cortex (V1), a phenomenon termed “blindsight”. Studies on animal models (cat and monkey) show that the age when the lesion occurs determines the extent of residual visual capacities. Much less is known about the functional and underlying neuronal repercussions of early cortical damage in humans. We measured sensitivity to several visual tasks in four children with congenital unilateral brain lesions that severely affected optic radiations, and in another group of three children with similar lesions, acquired in childhood. In two of the congenital patients, we measured blood oxygenation level dependent (BOLD) activity in response to stimulation of each visual field quadrants. Results show clear evidence of residual unconscious processing of position, orientation and motion of visual stimuli displayed in the scotoma of congenitally lesioned children, but not in the children with acquired lesions. The calcarine cortical BOLD responses were abnormally elicited by stimulation of the ipsilateral visual field and in the scotoma region, demonstrating a profound neuronal reorganization. In conclusion, our data suggest that congenital lesions can trigger massive reorganization of the visual system to alleviate functional effects of early brain insults.

Visual experience and blindsight: a methodological review

Blindsight is classically defined as residual visual capacity, e.g., to detect and identify visual stimuli, in the total absence of perceptual awareness following lesions to V1. However, whereas most experiments have investigated what blindsight patients can and cannot do, the literature contains several, often contradictory, remarks about remaining visual experience. This review examines closer these remarks as well as experiments that directly approach the nature of possibly spared visual experiences in blindsight.

Non-invasive alternating current stimulation improves vision in optic neuropathy

Partial blindness after visual system damage is considered irreversible, yet the brain has residual visual capacities and considerable plasticity potential. We now applied non-invasive alternating current stimulation (ACS) to the visual system of patients with optic nerve damage with the aim to induce recovery of visual functions. In a prospective, double-blind, randomized, placebo-controlled clinical trial patients with several year old partial optic nerve lesions were treated with ACS (n = 12) or placebo-stimulation (n = 10). ACS was delivered transorbitally for 40 minutes on 10 days. Visual outcome measures and EEG were measured before and after treatment. ACS, but not placebo, led to significant improvement of a visual field detection deficit by 69%, and also significantly improved temporal processing of visual stimuli, detection performance in static perimetry, and visual acuity. These changes were associated with alpha-band changes in the EEG power spectra. Visual improvements were stable for at least 2-months. ACS can induce vision restoration many years after optic neuropathy. Though the mechanism is still unclear, EEG changes indicate increased synchronization in posterior brain regions. The present study provides Class Ib evidence that non-invasive transorbital ACS is well tolerated and improves visual function in optic neuropathy.

Visual activation of extra-striate cortex in the absence of V1 activation

When the primary visual cortex (V1) is damaged, there are a number of alternative pathways that can carry visual information from the eyes to extrastriate visual areas. Damage to the visual cortex from trauma or infarct is often unilateral, extensive and includes gray matter and white matter tracts, which can disrupt other routes to residual visual function. We report an unusual young patient, SBR, who has bilateral damage to the gray matter of V1, sparing the adjacent white matter and surrounding visual areas. Using functional magnetic resonance imaging (fMRI), we show that area MT+/V5 is activated bilaterally to visual stimulation, while no significant activity could be measured in V1. Additionally, the white matter tracts between the lateral geniculate nucleus (LGN) and V1 appear to show some degeneration, while the tracts between LGN and MT+/V5 do not differ from controls. Furthermore, the bilateral nature of the damage suggests that residual visual capacity does not result from strengthened interhemispheric connections. The very specific lesion in SBR suggests that the ipsilateral connection between LGN and MT+/V5 may be important for residual visual function in the presence of damage to V1.

The anatomy of blindsight

Part of every neurological examination is an assessment of the visual field, obtained by asking patients to detect the presence of test targets on a defined background. Clinicians use either visual field testing to confrontation or more careful mapping and quantification of sensitivity of the visual field using automated perimetry. All of these approaches rely on the patient indicating whether they are aware of the presence of a test target at a particular location. Such testing can establish the presence of scotomas or blind regions of the visual field, where patients report that they do not perceive anything presented in such regions. Systematic correspondences between the location of visual field defects and the site of brain damage in the occipital lobe are sufficient to permit determination of a retinotopic map or projection of the retinal image onto what is now known as primary visual cortex (V1) on the medial surface of the occipital lobe (Inouye, 1909). Damage to V1 is thus associated with a lack of awareness for stimuli presented at corresponding points in the visual field, consistent with a role for V1 in visual awareness (Rees, 2007). However, during visual field testing, few if any clinicians would routinely press their patients to try and guess properties of stimuli that they resolutely deny being able to see when they are presented in a scotoma. But, when such a systematic investigation is performed using forced-choice procedures, remarkably, some patients show residual visual capacity in their blind field. These patients are able to perform certain discriminations and localizations better than chance in the acknowledged absence of awareness. This ability has become known as ‘blindsight’. We …

Visual function of a patient with advanced adrenoleukodystrophy: Comparison of luminance and color contrast sensitivities

We assessed achromatic luminance and isoluminant chromatic contrast sensitivity functions of a 20-year-old male. He showed severe motor and intellectual disabilities after advanced adrenoleukodystrophy, which started at the age of 7. Optokinetic nystagmus (OKN) to drifting gratings was used to assess his contrast sensitivities. Although the achromatic luminance contrast sensitivities were lower over the entire range of spatial frequencies tested than those of the healthy adults, they were preserved to the level comparable to healthy 7-year-old children, except for the frequency of 1 and 4 cycles/degree. In contrast, both of the red–green and blue chromatic contrast sensitivities were remarkably lower in all frequency range compare to healthy children and adults. These results indicate that it is possible for even an advanced case of ALD to show residual visual capacity that was preserved to a remarkable extent.

Increased sensitivity after repeated stimulation of residual spatial channels in blindsight

Lesions of the occipital cortex result in areas of cortical blindness affecting the corresponding regions of the patient's visual field. The traditional view is that, aside from some spontaneous recovery in the first few months after the damage, when acute effects have subsided the areas of blindness are absolute and permanent. It has been found, however, that within such field defects some residual visual capacities may persist in the absence of acknowledged awareness by the subject (blindsight type 1) or impaired awareness (type 2). Neuronal pathways mediating blindsight have a specific and narrow spatial and temporal bandwidth. A group of cortically blind patients (n = 12) carried out a daily detection "training" task over a 3-month period, discriminating grating visual stimuli optimally configured for blindsight from homogeneous luminance-matched stimuli. No feedback was given during the training. Assessment of training was by psychophysical measurements carried out before and after training and included detection of a range of spatial frequencies (0.5-7 cycles per degree), contrast detection at 1 cycle per degree, clinical perimetry, and subjective estimates of visual field defect. The results show that repeated stimulation by appropriate visual stimuli can result in improvements in visual sensitivities in the very depths of the field defect.

The role of spared calcarine cortex and lateral occipital cortex in the responses of human hemianopes to visual motion.

Some patients, who are rendered perimetrically blind in one hemifield by cortical lesions, nevertheless exhibit residual visual capacities within their field defects. The neural mechanism that mediates the residual visual responses has remained the topic of considerable debate. One explanation posits the subcortical visual pathways that bypass the primary visual cortex and innervate the extrastriate visual areas as the substrate that underlies the residual vision. The other explanation is that small islands of the primary visual cortex remain intact and provide the signals for residual vision. We have performed behavioral and functional magnetic resonance imaging experiments to investigate the validity of the two explanations of residual vision. Our behavioral experiments indicated that of the seven hemianopes tested, two had the ability to discriminate the direction of a drifting grating. This residual visual response was shown with fMRI to be the result of spared islands of calcarine cortical activity in one of the hemianopes, whereas only lateral occipital activity was documented in the other patient. These results indicate that the underlying neural correlates of residual vision can vary between patients. Moreover, our study emphasizes the necessity of ruling out the presence of islands of preserved function and primary visual cortex before assigning residual visual capacities to the properties of visual pathways that bypass the primary visual cortex.

Contrast sensitivity of patients with severe motor and intellectual disabilities and cerebral visual impairment.

We attempt to evaluate the residual visual capacities of nine patients (seven males and two females; age range 4 to 35 years, mean 13.8 +/- 9.98) with cerebral visual impairment coupled with severe motor and intellectual disabilities by their contrast sensitivities to sine-wave gratings. Two methods were used for detecting the occurrence of ocular responses to stimuli: (1) detection of optokinetic nystagmus to drifting sinusoidal gratings by naked-eye observation and electronystagmography and (2) detection of ocular pursuit for a drifting Gabor patch by naked-eye observation. We succeeded in measuring the sensitivities of eight cases. For the remaining one case, only the Gabor method could be applied. Most cases showed low contrast sensitivity in both higher (2 and 4 cycles/degree) and lower (0.125 and 0.25 cycles/degree) spatial frequencies and relatively high contrast sensitivity in the middle (0.5 and 1 cycle/degree) range of spatial frequencies. We conclude that the residual visual capacities of patients with severe motor and intellectual disabilities and cerebral visual impairment can be measured fairly accurately by these behavioral methods.

Chapter 23 ‘Seeing’ in the blind hemifield following hemispherectomy

Destruction of the striate cortex has traditionally been thought to lead to permanent blindness in the contralateral visual field and to the dogma that this region is indispensable for vision in primates. For over 25 years now, evidence has been accumulating that hemianopic human subjects and monkeys possess wide-ranging residual visual capacities or 'blindsight' in the blind part of their visual field. For some researchers, isolated islands of the striate cortex have been associated with patches of degraded vision and made responsible for blindisight. Artefacts such as light scatter, criterion effects, macular sparing, eccentric fixation and minute eye movements have also been linked with the residual vision. For others, the fact that certain aspects of the visual information can be processed without the geniculostriate pathway suggests mediation by the visual subsystems such as extrastriate visual cortical areas which receive visual information via subcortical pathways, that escaped the cortical damage. Subjects who have had a whole cerebral hemisphere removed or disconnected (for the treatment of uncontrollable epilepsy) and who show residual vision in their blind field offer a remarkable opportunity to help clear the controversy regarding the neural substrate of blindsight. Because it is certain that no functional striate or extrastriate cortex remains on the ablated side, these subjects have contributed significantly to identifying the critical pathways involved in blindsight.

Stereological evaluation of substantia nigra cell number in normal and hemispherectomized monkeys

The assessment of the anatomical consequences of cortical lesions on subcortical visual relays is necessary to further understand residual visual capacities. Unbiased stereological techniques were used to evaluate cell numbers in the substantia nigra (SN), a structure involved in the control of saccadic eye movements. Cell numbers were very similar in the ipsi- and contralateral SN of the hemispherectomized animal (329,926 vs. 310,248). These numbers are close to what was observed in the normal monkey (300,130 and 320,859). In one case, part of the striatum was lesioned in addition to the cerebral hemisphere. Noticeable effects were observed in the SN ipsilateral to the cortical lesion: volume was reduced by 30.5% while the number of neurons, compared to the contralateral side, dropped by 43.2% (186,644 vs. 328,757). These results suggest that due to its anatomical sparing following hemispherectomy the SN, in addition to other subcortical structures, is in a prime position to modulate the spared saccadic behaviors seen after massive cortical injuries.

Consciousness lost and found: a neuropsychological exploration

1. Introduction 2. The unseen and the unknown 3. Deficits, degradation, and dissociations 4. The What? of consciousness 5. Animal consciousness - the problem of whether? 6. The memory commentary is NOW 7. Attributes and possible pathways of residual visual capacity 8. The evolutionary why? 9. The question of how? 10. And so... Appendix - Terminology