Visual contrast perception in visual snow syndrome reveals abnormal neural gain but not neural noise.

Visual snow syndrome is a neurological condition characterized by a persistent visual disturbance, visual snow, in conjunction with additional visual symptoms. Cortical hyperexcitability is a potential pathophysiological mechanism, which could be explained by increased gain in neural responses to visual input. Alternatively, neural noise in the visual pathway could be abnormally elevated. We assessed these two potential competing neural mechanisms in our studies of visual contrast perception. Cortical hyperexcitation also occurs in migraine, which commonly co-occurs with visual snow syndrome. Therefore, to determine whether the effect of visual snow syndrome can be distinguished from interictal migraine, we recruited four participant groups: controls, migraine alone, visual snow syndrome alone and visual snow syndrome with migraine. In the first experiment, we estimated internal noise in 20 controls, 21 migraine participants and 32 visual snow syndrome participants (16 with migraine) using a luminance increment detection task. In the second experiment, we estimated neural contrast gain in 21 controls, 22 migraine participants and 35 visual snow syndrome participants (16 with migraine) using tasks assessing sensitivity to changes in contrast from a reference. Contrast gain and sensitivity were measured for the putative parvocellular and 'on' and 'off' magnocellular pathways, respectively. We found that luminance increment thresholds and internal noise estimates were normal in both visual snow syndrome and migraine. Contrast gain measures for putative parvocellular processing and contrast sensitivity for putative off magnocellular processing were abnormally increased in visual snow syndrome, regardless of migraine status. Therefore, our results indicate that visual snow syndrome is characterized by increased neural contrast gain but not abnormal neural noise within the targeted pathways.

Impacts of older age on the temporal properties of collinear facilitation.

Collinear facilitation is a visual phenomenon by which the contrast detection threshold of a central target is reduced (facilitation) when placed equidistant between two high-contrast flankers. The neural mechanisms underpinning this phenomenon originate from feed-forward lateral facilitation between cell layers in V1 (slower) and feedback facilitation from extrastriate visual areas to V1 (faster). The strength of these contributions has been explored in younger adults by presenting the central target and flankers at varying timing offsets. Here, we investigated the effects of older age on collinear facilitation with flankers presented in sync, before, and after target onset, to allow the inference of any characteristic effect of older age on feed-forward and feedback facilitatory mechanisms. Seventeen older and 19 younger observers participated. Our data confirms previous findings of an age-related reduction in facilitation when flankers and target occur at synchrony, but no age difference was found at other timings. Marked interindividual variability in facilitation for the different flanker onset timings was present, which was repeatable within individuals. Further research is required to ascertain the mechanistic underpinnings for different facilitation profiles between individuals. Longitudinal study across an individual's life span is needed to determine whether an individual's facilitation profile changes with age.

Daily vision testing can expose the prodromal phase of migraine.

Background Several visual tasks have been proposed as indirect assays of the balance between cortical inhibition and excitation in migraine. This study aimed to determine whether daily measurement of performance on such tasks can reveal perceptual changes in the build up to migraine events. Methods Visual performance was measured daily at home in 16 non-headache controls and 18 individuals with migraine using a testing protocol on a portable tablet device. Observers performed two tasks: luminance increment detection in spatial luminance noise and centre surround contrast suppression. Results Luminance thresholds were reduced in migraine compared to control groups ( p < 0.05), but thresholds did not alter across the migraine cycle; while headache-free, centre-surround contrast suppression was stronger for the migraine group relative to controls ( p < 0.05). Surround suppression weakened at around 48 hours prior to a migraine attack and strengthened to approach their headache-free levels by 24 hours post-migraine (main effect of timing, p < 0.05). Conclusions Daily portable testing of vision enabled insight into perceptual performance in the lead up to migraine events, a time point that is typically difficult to capture experimentally. Perceptual surround suppression of contrast fluctuates during the migraine cycle, supporting the utility of this measure as an indirect, non-invasive assay of the balance between cortical inhibition and excitation.

Spatial vision in older adults: perceptual changes and neural bases.

PURPOSE: The number of older adults is rapidly increasing internationally, leading to a significant increase in research on how healthy ageing impacts vision. Most clinical assessments of spatial vision involve simple detection (letter acuity, grating contrast sensitivity, perimetry). However, most natural visual environments are more spatially complicated, requiring contrast discrimination, and the delineation of object boundaries and contours, which are typically present on non-uniform backgrounds. In this review we discuss recent research that reports on the effects of normal ageing on these more complex visual functions, specifically in the context of recent neurophysiological studies. RECENT FINDINGS: Recent research has concentrated on understanding the effects of healthy ageing on neural responses within the visual pathway in animal models. Such neurophysiological research has led to numerous, subsequently tested, hypotheses regarding the likely impact of healthy human ageing on specific aspects of spatial vision. SUMMARY: Healthy normal ageing impacts significantly on spatial visual information processing from the retina through to visual cortex. Some human data validates that obtained from studies of animal physiology, however some findings indicate that rethinking of presumed neural substrates is required. Notably, not all spatial visual processes are altered by age. Healthy normal ageing impacts significantly on some spatial visual processes (in particular centre-surround tasks), but leaves contrast discrimination, contrast adaptation, and orientation discrimination relatively intact. The study of older adult vision contributes to knowledge of the brain mechanisms altered by the ageing process, can provide practical information regarding visual environments that older adults may find challenging, and may lead to new methods of assessing visual performance in clinical environments.

Older age results in difficulties separating auditory and visual signals in time.

Previous research provides conflicting evidence regarding whether older adults have altered tolerance to timing differences between auditory and visual events. We examine the potential impact of age-related unisensory decline on audiovisual synchrony perception. Fifteen younger (21-32 years) and 13 older (60-72 years) adults participated. To assess unisensory sensitivity, visual Gabor contrast detection thresholds and auditory masked tone pip detection thresholds were measured. Four multisensory conditions were then tested: suprathreshold and near-threshold stimuli (based on individual unisensory psychometric functions), each tested with a masked tone pip stimuli at 0.5 and 4 kHz sound frequencies. Two audiovisual pairs (one synchronous, the other asynchronous) were presented in a two-interval forced-choice procedure, with observers identifying the interval containing the asynchronous stimulus. Older adults required a larger physical asynchrony to perceive the stimuli as asynchronous, particularly for low frequency sounds. Our results demonstrate that the impact of age on audiovisual synchrony perception cannot be explained by decline in unisensory sensitivity alone.

Improving Understanding of Visual Snow by Quantifying its Appearance and Effect on Vision.

Purpose: Visual snow is the hallmark of the neurological condition visual snow syndrome (VSS) but the characteristics of the visual snow percept remain poorly defined. This study aimed to quantify its appearance, interobserver variability, and effect on measured visual performance and self-reported visual quality. Methods: Twenty-three participants with VSS estimated their visual snow dot size, separation, luminance, and flicker rate by matching to a simulation. To assess whether visual snow masks vision, we compared pattern discrimination thresholds for textures that were similar in spatial scale to visual snow as well as more coarse than visual snow, in participants with VSS, and with and without external noise simulating visual snow in 23 controls. Results: Mean and 95% confidence intervals for visual snow appearance were: size (6.0, 5.8-6.3 arcseconds), separation (2.0, 1.7-2.3 arcmin), luminance (72.4, 58.1-86.8 cd/m2), and flicker rate (25.8, 18.9-32.8 frames per image at 120 hertz [Hz]). Participants with finer dot spacing estimates also reported greater visibility of their visual snow (τb = -0.41, 95% confidence interval [CI] = -0.62 to -0.13, P = 0.01). In controls, adding simulated fine-scale visual snow to textures increased thresholds for fine but not coarse textures (F(1, 22) = 4.98, P = 0.036, ηp2 = 0.19). In VSS, thresholds for fine and coarse textures were similar (t(22) = 0.54, P = 0.60), suggesting that inherent visual snow does not act like external noise in controls. Conclusions: Our quantitative estimates of visual snow constrain its likely neural origins, may aid differential diagnosis, and inform future investigations of how it affects vision. Methods to quantify visual snow are needed for evaluation of potential treatments.

Aging effects on collinear facilitation.

Normal aging has been shown to alter performance on several suprathreshold spatial tasks such as contour integration and perceptual measures of center-surround interactions. The purpose of this study was to investigate the effects of aging on collinear facilitation. Despite all related lateral interactions that are presumed to involve neural architecture within primary visual cortex, collinear facilitation differs from contour integration and surround suppression tasks in that it is a purely foveal, threshold phenomenon. Collinear facilitation was measured for 20 younger (19-31 years) and 15 older (59-71 years) adults with measures repeated over two identical test sessions. Contrast thresholds were measured for a central Gabor patch in the presence of flankers of varying interelement distances and orientations. A reduced magnitude of facilitation was found for the older observers. Our results demonstrate abnormalities of spatial interactions in older adults.

Relating the cortical visual contrast gain response to spectroscopy-measured excitatory and inhibitory metabolites in people who experience migraine.

OBJECTIVE: This study aimed to determine whether the visual response to flickering checkerboard patterns measured using electroencephalography (EEG) relate to excitatory or inhibitory metabolite levels measured using ultra-high (7Tesla/7T) magnetic resonance spectroscopy (MRS). BACKGROUND: Electrophysiological studies have shown altered visual cortical response amplitudes and contrast gain responses to high contrast flickering patterns in people with migraine. These contrast response anomalies have been argued to represent an imbalance between cortical inhibition and excitation, however the specific mechanism has not been elucidated. METHODS: MRS-measured metabolite levels were obtained from the occipital cortex of 18 participants with migraine and 18 non-headache controls. EEG contrast gain response functions were collected on separate days from a subset of 10 participants with migraine and 12 non-headache controls. Case-control outcome measures were statistically compared between groups both before and after checkboard exposure. RESULTS: No significant difference in GABA and glutamate levels were found between groups nor checkerboard timepoint. Glucose levels were significantly reduced after checkerboard exposure in both participant groups. There was no metabolic signature in visual cortex in response to high-contrast flickering checkboards that distinguished those with migraine and without. There was also no correlation between MRS and EEG measurements in response to the flickering checkerboard. CONCLUSION: Our findings suggest that the mechanisms driving contrast-flickering stimulus aversion are not simplistically reflected by gross changes in metabolic activity in the primary visual cortex.

A Study Protocol for an Open-Label Feasibility Treatment Trial of Visual Snow Syndrome With Transcranial Magnetic Stimulation.

Background: Visual Snow (VS) syndrome is believed to be due to aberrant central visual processing. Positron Emission Tomography (PET) brain imaging and visual evoked potential studies provide evidence for excessive neuronal activity in the medial temporal lobe, specifically the lingual gyrus, and suggest the VS syndrome is a hyperexcitability syndrome. These data provide the basis for consideration of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for the VS syndrome. Objective: To publish the study protocol for a pilot study underway at the University of Colorado School of Medicine to investigate the use of rTMS intervention to improve symptoms and visual dysfunction associated with VS. The study aims to determine the adverse events and drop-out rate, evaluate performance of outcome measures, including a novel VS symptom scale, and describe changes in outcomes associated with treatment. Methods and Design: Up to 10 participants meeting criteria for VS syndrome, age 19-65 years, will undergo an open-label intervention consisting of 10 rTMS sessions, occurring 5 days a week over a 2-week period. Participants will complete pre-treatment and post-treatment assessments that include: the Colorado Visual Snow Scale (CVSS), the National Eye Institute Visual Functional Questionnaire-25 (VFQ-25), the General Anxiety Disorder-7 scale (GAD-7), and three psychophysical visual processing tasks. Discussion: Knowledge gained from this pilot study will inform future study planning and provide valuable lessons for future investigation of rTMS for the VS syndrome. An overview of study proceedings thus far demonstrates recruitment challenges associated with the COVID-19 pandemic, and additional challenges that are unique to the VS syndrome and to treatment schedules associated with TMS. Registration: This study has been approved by the Colorado Multiple Institutional Review Board. ClinicalTrials.gov Identifier: NCT04925232.

Illusory Motion Perception Is Associated with Contrast Discrimination but Not Motion Sensitivity, Self-Reported Visual Discomfort, or Migraine Status.

Purpose: Altered visual processing of motion and contrast has been previously reported in people with migraine. One possible manifestation of this altered visual processing is increased self-reported susceptibility to visual illusions of contrast and motion. Here, we use the Fraser-Wilcox illusion to explore individual differences in motion illusion strength in people with and without migraine. The motion-inducing mechanisms of the Fraser-Wilcox illusion are purported to be contrast dependent. To better understand the mechanisms of the illusion, as well as visual processing anomalies in migraine, we explored whether migraine status, susceptibility to visual discomfort, contrast discrimination, or motion sensitivity are related to quantified motion illusion strength. Methods: Thirty-six (16 with aura, 20 without aura) people with migraine and 20 headache-free controls participated. Outcome measures were motion illusion strength (the physical motion speed that counterbalanced the illusory motion), motion sensitivity, and contrast discrimination thresholds (measured for each contrast pair that formed part of the illusory motion stimulus). Typical daily visual discomfort was self-reported via questionnaire. Results: Motion illusion strength was negatively correlated with contrast discrimination threshold (r = -0.271, P = 0.04) but was not associated with motion sensitivity or migraine status. People with migraine with aura reported experiencing visual discomfort more frequently than the control group (P = 0.001). Self-reported visual discomfort did not relate to quantified perceptual motion illusion strength. Conclusions: Individuals with better contrast discrimination tend to perceive faster illusory motion regardless of migraine status.

Orientation-dependency of perceptual surround suppression and orientation decoding of centre-surround stimuli are preserved with healthy ageing.

A key visual neuronal property that is mirrored in human behaviour is centre-surround contrast suppression, which is orientation-dependent. When a target is embedded in a high-contrast surround, the centre appears reduced in contrast, the magnitude of which depends on the relative orientation between centre and surround. Previous reports demonstrate changes in perceptual surround suppression with ageing; however, whether the orientation-dependency of surround suppression is impacted by ageing has not been explored. Here, we tested 18 younger (aged 19-33) and 18 older (aged 60-77) adults. Perceptual surround suppression was stronger for parallel than orthogonal stimuli; however contrary to previous work, here we found no difference in perceptual suppression strength between age-groups. In the same participants, we measured event-related potentials (ERPs) and conducted multivariate pattern analysis to confirm that parallel and orthogonal centre-surround stimuli elicit distinguishable brain activity, predominantly over occipital areas. Despite a delay in the first prominent ERP component (P1) in response to each pattern, older adults showed similar decoding of orientation information (i.e. distinguish between parallel and orthogonal centre-surround stimuli from 70 ms post-stimulus onset) as younger adults. This suggests that sufficient information to distinguish orientation in centre-surround stimuli becomes available to the older human brain as early as in younger adults.

Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events.

Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.

Highly Enantioselective Synthesis Using Prolinol as a Chiral Auxiliary: Silver-Mediated Synthesis of Axially Chiral Vinylallenes and Subsequent (Hetero)-Diels-Alder Reactions.

Using (S)-prolinol as a chiral auxiliary, axially chiral vinylallenes with excellent enantiopurity (up to >99% enantiomeric excess (ee)) were readily prepared from optically pure propargylamines in the presence of AgNO3 under microwave irradiation. Subsequent (hetero)-Diels-Alder reaction of these axially chiral vinylallenes with azodicarboxylates or maleimides on water demonstrates excellent axial-to-point chirality transfer (up to 99% ee).

Audiovisual Temporal Perception in Aging: The Role of Multisensory Integration and Age-Related Sensory Loss.

Within each sensory modality, age-related deficits in temporal perception contribute to the difficulties older adults experience when performing everyday tasks. Since perceptual experience is inherently multisensory, older adults also face the added challenge of appropriately integrating or segregating the auditory and visual cues present in our dynamic environment into coherent representations of distinct objects. As such, many studies have investigated how older adults perform when integrating temporal information across audition and vision. This review covers both direct judgments about temporal information (the sound-induced flash illusion, temporal order, perceived synchrony, and temporal rate discrimination) and judgments regarding stimuli containing temporal information (the audiovisual bounce effect and speech perception). Although an age-related increase in integration has been demonstrated on a variety of tasks, research specifically investigating the ability of older adults to integrate temporal auditory and visual cues has produced disparate results. In this short review, we explore what factors could underlie these divergent findings. We conclude that both task-specific differences and age-related sensory loss play a role in the reported disparity in age-related effects on the integration of auditory and visual temporal information.

Spatio-temporal patterns of event-related potentials related to audiovisual synchrony judgments in older adults.

Older adults have altered perception of the relative timing between auditory and visual stimuli, even when stimuli are scaled to equate detectability. To help understand why, this study investigated the neural correlates of audiovisual synchrony judgments in older adults using electroencephalography (EEG). Fourteen younger (18-32 year old) and 16 older (61-74 year old) adults performed an audiovisual synchrony judgment task on flash-pip stimuli while EEG was recorded. All participants were assessed to have healthy vision and hearing for their age. Observers responded to whether audiovisual pairs were perceived as synchronous or asynchronous via a button press. The results showed that the onset of predictive sensory information for synchrony judgments was not different between groups. Channels over auditory areas contributed more to this predictive sensory information than visual areas. The spatial-temporal profile of the EEG activity also indicates that older adults used different resources to maintain a similar level of performance in audiovisual synchrony judgments compared with younger adults.

Behavioral measures of cortical hyperexcitability assessed in people who experience visual snow.

OBJECTIVE: To determine whether visual perceptual measures in people who experience visual snow are consistent with an imbalance between inhibition and excitation in visual cortex. METHODS: Sixteen patients with visual snow and 18 controls participated. Four visual tasks were included: center-surround contrast matching, luminance increment detection in noise, and global form and global motion coherence thresholds. Neuronal architecture capable of encoding the luminance and contrast stimuli is present within primary visual cortex, whereas the extraction of global motion and form signals requires extrastriate processing. All these tasks have been used previously to investigate the balance between inhibition and excitation within the visual system in both healthy and diseased states. RESULTS: The visual snow group demonstrated reduced center-surround contrast suppression (p = 0.03) and elevated luminance increment thresholds in noise (p = 0.02). Groups did not differ on the global form or global motion task. CONCLUSION: Our study demonstrates that visual perceptual measures involving the suprathreshold processing of contrast and luminance are abnormal in a group of individuals with visual snow. Our data are consistent with elevated excitability in primary visual cortex; however, further research is required to provide more direct evidence for this proposed mechanism. The ability to measure perceptual differences in visual snow reveals promise for the future development of clinical tests to assist in visual snow diagnosis and possibly a method for quantitatively assaying any benefits of treatments.

Reduced audiovisual recalibration in the elderly.

Perceived synchrony of visual and auditory signals can be altered by exposure to a stream of temporally offset stimulus pairs. Previous literature suggests that adapting to audiovisual temporal offsets is an important recalibration to correctly combine audiovisual stimuli into a single percept across a range of source distances. Healthy aging results in synchrony perception over a wider range of temporally offset visual and auditory signals, independent of age-related unisensory declines in vision and hearing sensitivities. However, the impact of aging on audiovisual recalibration is unknown. Audiovisual synchrony perception for sound-lead and sound-lag stimuli was measured for 15 younger (22-32 years old) and 15 older (64-74 years old) healthy adults using a method-of-constant-stimuli, after adapting to a stream of visual and auditory pairs. The adaptation pairs were either synchronous or asynchronous (sound-lag of 230 ms). The adaptation effect for each observer was computed as the shift in the mean of the individually fitted psychometric functions after adapting to asynchrony. Post-adaptation to synchrony, the younger and older observers had average window widths (±standard deviation) of 326 (±80) and 448 (±105) ms, respectively. There was no adaptation effect for sound-lead pairs. Both the younger and older observers, however, perceived more sound-lag pairs as synchronous. The magnitude of the adaptation effect in the older observers was not correlated with how often they saw the adapting sound-lag stimuli as asynchronous. Our finding demonstrates that audiovisual synchrony perception adapts less with advancing age.