Excitation-Inhibition Imbalance in Migraine: From Neurotransmitters to Brain Oscillations.

Migraine is among the most common and debilitating neurological disorders typically affecting people of working age. It is characterised by a unilateral, pulsating headache often associated with severe pain. Despite the intensive research, there is still little understanding of the pathophysiology of migraine. At the electrophysiological level, altered oscillatory parameters have been reported within the alpha and gamma bands. At the molecular level, altered glutamate and GABA concentrations have been reported. However, there has been little cross-talk between these lines of research. Thus, the relationship between oscillatory activity and neurotransmitter concentrations remains to be empirically traced. Importantly, how these indices link back to altered sensory processing has to be clearly established as yet. Accordingly, pharmacologic treatments have been mostly symptom-based, and yet sometimes proving ineffective in resolving pain or related issues. This review provides an integrative theoretical framework of excitation-inhibition imbalance for the understanding of current evidence and to address outstanding questions concerning the pathophysiology of migraine. We propose the use of computational modelling for the rigorous formulation of testable hypotheses on mechanisms of homeostatic imbalance and for the development of mechanism-based pharmacological treatments and neurostimulation interventions.

Virtual Reality for Vision Science.

Virtual reality (VR) allows us to create visual stimuli that are both immersive and reactive. VR provides many new opportunities in vision science. In particular, it allows us to present wide field-of-view, immersive visual stimuli; for observers to actively explore the environments that we create; and for us to understand how visual information is used in the control of behaviour. In contrast with traditional psychophysical experiments, VR provides much greater flexibility in creating environments and tasks that are more closely aligned with our everyday experience. These benefits of VR are of particular value in developing our theories of the behavioural goals of the visual system and explaining how visual information is processed to achieve these goals. The use of VR in vision science presents a number of technical challenges, relating to how the available software and hardware limit our ability to accurately specify the visual information that defines our virtual environments and the interpretation of data gathered in experiments with a freely moving observer in a responsive environment.

Luminance contrast provides metric depth information.

The perception of depth from retinal images depends on information from multiple visual cues. One potential depth cue is the statistical relationship between luminance and distance; darker points in a local region of an image tend to be farther away than brighter points. We establish that this statistical relationship acts as a quantitative cue to depth. We show that luminance variations affect depth in naturalistic scenes containing multiple cues to depth. This occurred when the correlation between variations of luminance and depth was manipulated within an object, but not between objects. This is consistent with the local nature of the statistical relationship in natural scenes. We also showed that perceived depth increases as contrast is increased, but only when the depth signalled by luminance and binocular disparity are consistent. Our results show that the negative correlation between luminance and distance, as found under diffuse lighting, provides a depth cue that is combined with depth from binocular disparity, in a way that is consistent with the simultaneous estimation of surface depth and reflectance variations. Adopting more complex lighting models such as ambient occlusion in computer rendering will thus contribute to the accuracy as well as the aesthetic appearance of three-dimensional graphics.

Visual Field Loss: Integrating Overlayed Information to Increase the Effective Field of View.

Visual field loss is a debilitating impairment that can impact normal daily activities. The advancement of augmented and virtual realities brings opportunities for potential substitutive technologies for visual field loss. Here we outline a conceptual approach to increasing the amount of useful information by overlaying the blind field into the sighted field. In this proof-of-concept experiment, 33 observers were allocated to either a left or right blind condition (with a simulated scotoma). All observers completed a line bisection task in all three conditions (baseline, scotoma, manipulation), with the baseline condition always completed first. The scotoma condition (baseline with the addition of a simulated scotoma) and the manipulated condition (baseline with the addition of a simulated scotoma, and a "minified window overlay") were randomised in order of presentation. Predictably, our results show that a simulated scotoma impaired performance on the task. However, observers were able to make use the overlay to improve their estimation of the line's midpoint. Our results show that a substitutive augmentation of this type improved accuracy in estimating the midpoint of a line with a (simulated) scotoma.

Robust natural depth for anticorrelated random dot stereogram for edge stimuli, but minimal reversed depth for embedded circular stimuli, irrespective of eccentricity.

The small differences between the images formed in our left and right eyes are an important cue to the three-dimensional structure of scenes. These disparities are encoded by binocular neurons in the visual cortex. At the earliest stage of processing, these respond to binocular correlation between images. We assessed the perception of depth in anticorrelated stimuli, in which the contrast polarity in one eye is reversed, as a function of their location in the retinal image, and their depth configuration (a horizontal edge or a circle surrounded by an annulus) We found that, regardless of stimulus eccentricity, participants perceived depth in the natural direction for edge stimuli, and weakened, reversed depth for circular stimuli.

Increasing interhemispheric connectivity between human visual motion areas uncovers asymmetric sensitivity to horizontal motion.

Our conscious perceptual experience relies on a hierarchical process involving integration of low-level sensory encoding and higher-order sensory selection.1 This hierarchical process may scale at different levels of brain functioning, including integration of information between the hemispheres.2-5 Here, we test this hypothesis for the perception of visual motion stimuli. Across 3 experiments, we manipulated the connectivity between the left and right visual motion complexes (V5/MT+) responsible for horizontal motion perception2,3 by means of transcranial magnetic stimulation (TMS).4,5 We found that enhancing the strength of connections from the left to the right V5/MT+, by inducing spike-timing-dependent plasticity6 in this pathway, increased sensitivity to horizontal motion. These changes were present immediately and lasted at least 90 min after intervention. Notably, little perceptual changes were observed when strengthening connections from the right to the left V5/MT+. Furthermore, we found that this asymmetric modulation was mirrored by an asymmetric perceptual bias in the direction of the horizontal motion. Overall, observers were biased toward leftward relative to rightward motion direction. Crucially, following the strengthening of the connections from right to left V5/MT+, this bias could be momentarily reversed. These results suggest that the projections connecting left and right V5/MT+ in the human visual cortex are asymmetrical, subtending a hierarchical role of hemispheric specialization7-10 favoring left-to-right hemisphere processing for integrating local sensory input into coherent global motion perception.

Saccadic eye movements are deployed faster for salient facial stimuli, but are relatively indifferent to their emotional content.

The present study explores the threat bias for fearful facial expressions using saccadic latency, with a particular focus on the role of low-level facial information, including spatial frequency and contrast. In a simple localisation task, participants were presented with spatially-filtered versions of neutral, fearful, angry and happy faces. Together, our findings show that saccadic responses are not biased toward fearful expressions compared to neutral, angry or happy counterparts, regardless of their spatial frequency content. Saccadic response times are, however, significantly influenced by the spatial frequency and contrast of facial stimuli. We discuss the implications of these findings for the threat bias literature, and the extent to which image processing can be expected to influence behavioural responses to socially-relevant facial stimuli.

Binocular Information Improves the Reliability and Consistency of Pictorial Relief.

Binocular disparity is an important cue to three-dimensional shape. We assessed the contribution of this cue to the reliability and consistency of depth in stereoscopic photographs of natural scenes. Observers viewed photographs of cluttered scenes while adjusting a gauge figure to indicate the apparent three-dimensional orientation of the surfaces of objects. The gauge figure was positioned on the surfaces of objects at multiple points in the scene, and settings were made under monocular and binocular, stereoscopic viewing. Settings were used to create a depth relief map, indicating the apparent three-dimensional structure of the scene. We found that binocular cues increased the magnitude of apparent depth, the reliability of settings across repeated measures, and the consistency of perceived depth across participants. These results show that binocular cues make an important contribution to the precise and accurate perception of depth in natural scenes that contain multiple pictorial cues.

Binocular vision supports the development of scene segmentation capabilities: Evidence from a deep learning model.

The application of deep learning techniques has led to substantial progress in solving a number of critical problems in machine vision, including fundamental problems of scene segmentation and depth estimation. Here, we report a novel deep neural network model, capable of simultaneous scene segmentation and depth estimation from a pair of binocular images. By manipulating the arrangement of binocular image pairs, presenting the model with standard left-right image pairs, identical image pairs or swapped left-right images, we show that performance levels depend on the presence of appropriate binocular image arrangements. Segmentation and depth estimation performance are both impaired when images are swapped. Segmentation performance levels are maintained, however, for identical image pairs, despite the absence of binocular disparity information. Critically, these performance levels exceed those found for an equivalent, monocularly trained, segmentation model. These results provide evidence that binocular image differences support both the direct recovery of depth and segmentation information, and the enhanced learning of monocular segmentation signals. This finding suggests that binocular vision may play an important role in visual development. Better understanding of this role may hold implications for the study and treatment of developmentally acquired perceptual impairments.

No Evidence of Reduced Contrast Sensitivity in Migraine-with-Aura for Large, Narrowband, Centrally Presented Noise-Masked Stimuli.

Individuals with migraine aura show differences in visual perception compared to control groups. Measures of contrast sensitivity have suggested that people with migraine aura are less able to exclude external visual noise, and that this relates to higher variability in neural processing. The current study compared contrast sensitivity in migraine with aura and control groups for narrow-band grating stimuli at 2 and 8 cycles/degree, masked by Gaussian white noise. We predicted that contrast sensitivity would be lower in the migraine with aura group at high noise levels. Contrast sensitivity was higher for the low spatial frequency stimuli, and decreased with the strength of the masking noise. We did not, however, find any evidence of reduced contrast sensitivity associated with migraine with aura. We propose alternative methods as a more targeted assessment of the role of neural noise and excitability as contributing factors to migraine aura.

Migraine Visual Aura and Cortical Spreading Depression-Linking Mathematical Models to Empirical Evidence.

This review describes the subjective experience of visual aura in migraine, outlines theoretical models of this phenomenon, and explores how these may be linked to neurochemical, electrophysiological, and psychophysical differences in sensory processing that have been reported in migraine with aura. Reaction-diffusion models have been used to model the hallucinations thought to arise from cortical spreading depolarisation and depression in migraine aura. One aim of this review is to make the underlying principles of these models accessible to a general readership. Cortical spreading depolarisation and depression in these models depends on the balance of the diffusion rate between excitation and inhibition and the occurrence of a large spike in activity to initiate spontaneous pattern formation. We review experimental evidence, including recordings of brain activity made during the aura and attack phase, self-reported triggers of migraine, and psychophysical studies of visual processing in migraine with aura, and how these might relate to mechanisms of excitability that make some people susceptible to aura. Increased cortical excitability, increased neural noise, and fluctuations in oscillatory activity across the migraine cycle are all factors that are likely to contribute to the occurrence of migraine aura. There remain many outstanding questions relating to the current limitations of both models and experimental evidence. Nevertheless, reaction-diffusion models, by providing an integrative theoretical framework, support the generation of testable experimental hypotheses to guide future research.

Suppression durations for facial expressions under breaking continuous flash suppression: effects of faces' low-level image properties.

Perceptual biases for fearful facial expressions are observed across many studies. According to the low-level, visual-based account of these biases, fear expressions are advantaged in some way due to their image properties, such as low spatial frequency content. However, there is a degree of empirical disagreement regarding the range of spatial frequency information responsible for perceptual biases. Breaking continuous flash suppression (b. CFS) has explored these effects, showing similar biases for detecting fearful facial expressions. Recent findings from a b. CFS study highlight the role of high, rather than low spatial frequency content in determining faces' visibility. The present study contributes to ongoing discussions regarding the efficacy of b. CFS, and shows that the visibility of facial expressions vary according to how they are normalised for physical contrast and spatially filtered. Findings show that physical contrast normalisation facilitates fear's detectability under b. CFS more than when normalised for apparent contrast, and that this effect is most pronounced when faces are high frequency filtered. Moreover, normalising faces' perceived contrast does not guarantee equality between expressions' visibility under b. CFS. Findings have important implications for the use of contrast normalisation, particularly regarding the extent to which contrast normalisation facilitates fear bias effects.

No effect of feedback, level of processing or stimulus presentation protocol on perceptual learning when easy and difficult trials are interleaved.

The role of feedback during training is a topic of great theoretical importance in perceptual learning. Feedback can be provided externally by the environment or internally by the observer. In order to evaluate the effectiveness of learning with internal versus external feedback, we performed a large multi-level experiment, varying the type of training task (Motion or Form), the level of processing (Local or Global), the presence of feedback (With or Without) and finally the method of stimulus presentation (Adaptive staircase or Method of constant stimuli). 140 participants were randomly assigned to one of ten groups and undertook 3 days of training in one condition only. Detection thresholds were measured daily before and after training with a pre- and post-assessment. A 75% detection threshold was calculated and used to estimate that day's training levels (65% and 85% accuracy for difficult and easy trials respectively). The group trained with MOCS were presented with predefined randomly interleaved easy and difficult trials ranging from 50% to 95% stimulus intensity. Our findings indicate that improvement was generally robust across training-tasks, processing levels and feedback conditions. This suggests that internal reinforcement is as effective as external feedback in a discrete-noise-paradigm for local and global tasks when easy and difficult trials are interleaved.

Contrast normalisation masks natural expression-related differences and artificially enhances the perceived salience of fear expressions.

Fearful facial expressions tend to be more salient than other expressions. This threat bias is to some extent driven by simple low-level image properties, rather than the high-level emotion interpretation of stimuli. It might be expected therefore that different expressions will, on average, have different physical contrasts. However, studies tend to normalise stimuli for RMS contrast, potentially removing a naturally-occurring difference in salience. We assessed whether images of faces differ in both physical and apparent contrast across expressions. We measured physical RMS contrast and the Fourier amplitude spectra of 5 emotional expressions prior to contrast normalisation. We also measured expression-related differences in perceived contrast. Fear expressions have a steeper Fourier amplitude slope compared to neutral and angry expressions, and consistently significantly lower contrast compared to other faces. This effect is more pronounced at higher spatial frequencies. With the exception of stimuli containing only low spatial frequencies, fear expressions appeared higher in contrast than a physically matched reference. These findings suggest that contrast normalisation artificially boosts the perceived salience of fear expressions; an effect that may account for perceptual biases observed for spatially filtered fear expressions.

Size and shape constancy in consumer virtual reality.

With the increase in popularity of consumer virtual reality headsets, for research and other applications, it is important to understand the accuracy of 3D perception in VR. We investigated the perceptual accuracy of near-field virtual distances using a size and shape constancy task, in two commercially available devices. Participants wore either the HTC Vive or the Oculus Rift and adjusted the size of a virtual stimulus to match the geometric qualities (size and depth) of a physical stimulus they were able to refer to haptically. The judgments participants made allowed for an indirect measure of their perception of the egocentric, virtual distance to the stimuli. The data show under-constancy and are consistent with research from carefully calibrated psychophysical techniques. There was no difference in the degree of constancy found in the two headsets. We conclude that consumer virtual reality headsets provide a sufficiently high degree of accuracy in distance perception, to allow them to be used confidently in future experimental vision science, and other research applications in psychology.

Impairment of cyclopean surface processing by disparity-defined masking stimuli.

Binocular disparity signals allow for the estimation of three-dimensional shape, even in the absence of monocular depth cues. The perception of such disparity-defined form depends, however, on the linkage of multiple disparity measurements over space. Performance limitations in cyclopean tasks thus inform us about errors arising in disparity measurement and difficulties in the linkage of such measurements. We used a cyclopean orientation discrimination task to examine the perception of disparity-defined form. Participants were presented with random-dot sinusoidal modulations in depth and asked to report whether they were clockwise or counter-clockwise rotated. To assess the effect of different noise structures on measurement and linkage processes, task performance was measured in the presence of binocular, random-dot masks, structured as either antiphase depth sinusoids, or as random distributions of dots in depth. For a fixed number of surface dots, the ratio of mask-to-surface dots was varied to obtain thresholds for orientation discrimination. Antiphase masks were found to be more effective than random depth masks, requiring a lower mask-to-surface dot ratio to inhibit performance. For antiphase masks, performance improved with decreased cyclopean frequency, increased disparity amplitude, and/or an increase in the total number of stimulus dots. Although a cross-correlation model of disparity measurement could account for antiphase mask performance, random depth masking effects were consistent with limitations in relative disparity processing. This suggests that performance is noise-limited for antiphase masks and complexity-limited for random masks. We propose that use of differing mask types may prove effective in understanding these distinct forms of impairment.

Stereoscopic depth adaptation from binocularly correlated versus anti-correlated noise: Test of an efficient coding theory of stereopsis.

Stereoscopic, or "3D" vision in humans is mediated by neurons sensitive to the disparities in the positions of objects in the two eyes' views. A disparity-sensitive neuron is typically characterized by its responses to left- and right-eye monocular signals, SL and SR, respectively. However, it can alternatively be characterized by sensitivity to the sum of the two eyes' inputs, S+ = SL + SR, and the difference, S- = SL - SR. Li and Atick's theory of efficient binocular encoding proposes that the S+ and S- signals can be separately weighted to maximize the efficiency with which binocular information is encoded. This adaptation changes each neuron's sensitivity and preferred binocular disparity, resulting in predicted effects on the perceived stereoscopic depth of objects. To test these predictions, we measured the apparent depth of a random-dot stereogram with an 'in-front' target following adaptation to binocularly correlated or anti-correlated horizontally-oriented grating stimuli, which reduce sensitivity to the S+ and S- signals, respectively, but which contain no conventional stereo-depth signals. The anti-correlated noise adaptation made the target appear relatively closer to the background than the correlated noise adaptation, with differences of up to 60%. We show how this finding can be accommodated by a standard model of binocular disparity processing, modified to incorporate the binocular adaptation suggested by Li and Atick's theory.

Spatial Frequency Tuning and Transfer of Perceptual Learning for Motion Coherence Reflects the Tuning Properties of Global Motion Processing.

Perceptual learning is typically highly specific to the stimuli and task used during training. However, recently, it has been shown that training on global motion can transfer to untrained tasks, reflecting the generalising properties of mechanisms at this level of processing. We investigated (i) if feedback was required for learning in a motion coherence task, (ii) the transfer across the spatial frequency of training on a global motion coherence task and (iii) the transfer of this training to a measure of contrast sensitivity. For our first experiment, two groups, with and without feedback, trained for ten days on a broadband motion coherence task. Results indicated that feedback was a requirement for robust learning. For the second experiment, training consisted of five days of direction discrimination using one of three motion coherence stimuli (where individual elements were comprised of either broadband Gaussian blobs or low- or high-frequency random-dot Gabor patches), with trial-by-trial auditory feedback. A pre- and post-training assessment was conducted for each of the three types of global motion coherence conditions and high and low spatial frequency contrast sensitivity (both without feedback). Our training paradigm was successful at eliciting improvement in the trained tasks over the five days. Post-training assessments found evidence of transfer for the motion coherence task exclusively for the group trained on low spatial frequency elements. For the contrast sensitivity tasks, improved performance was observed for low- and high-frequency stimuli, following motion coherence training with broadband stimuli, and for low-frequency stimuli, following low-frequency training. Our findings are consistent with perceptual learning, which depends on the global stage of motion processing in higher cortical areas, which is broadly tuned for spatial frequency, with a preference for low frequencies.

The effect of facial expression on contrast sensitivity: A behavioural investigation and extension of Hedger, Adams & Garner (2015).

It has been argued that rapid visual processing for fearful face expressions is driven by the fact that effective contrast is higher in these faces compared to other expressions, when the contrast sensitivity function is taken into account. This proposal has been upheld by data from image analyses, but is yet to be tested at the behavioural level. The present study conducts a traditional contrast sensitivity task for face images of various facial expressions. Findings show that visual contrast thresholds do not differ for different facial expressions We re-conduct analysis of faces' effective contrast, using the procedure developed by Hedger, Adams and Garner, and show that higher effective contrast in fearful face expressions relies on face images first being normalised for RMS contrast. When not normalised for RMS contrast, effective contrast in fear expressions is no different, or sometimes even lower, compared to other expressions. However, the effect of facial expression on detection in a backward masking study did not depend on the type of contrast normalisation used. These findings are discussed in relation to the implications of contrast normalisation on the salience of face expressions in behavioural and neurophysiological experiments, and also the extent that natural physical differences between facial stimuli are masked during stimulus standardisation and normalisation.