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.

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.

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.

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.

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.

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.

First- and second-order contributions to depth perception in anti-correlated random dot stereograms.

The binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed-depth has been found using anti-correlated random-dot stereograms (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed-depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter.

Typical Lateral Interactions, but Increased Contrast Sensitivity, in Migraine-With-Aura.

Individuals with migraine show differences in visual perception compared to control groups. It has been suggested that differences in lateral interactions between neurons might account for some of these differences. This study seeks to further establish the strength and spatial extent of excitatory and inhibitory interactions in migraine-with-aura using a classic lateral masking task. Observers indicated which of two intervals contained a centrally presented, vertical Gabor target of varying contrast. In separate blocks of trials, the target was presented alone or was flanked by two additional collinear, high contrast Gabors. Flanker distances varied between 1 and 12 wavelengths of the Gabor stimuli. Overall, contrast thresholds for the migraine group were lower than those in the control group. There was no difference in the degree of lateral interaction in the migraine group. These results are consistent with the previous work showing enhanced contrast sensitivity in migraine-with-aura for small, rapidly presented targets, and they suggest that impaired performance in global perceptual tasks in migraine may be attributed to difficulties in segmenting relevant from irrelevant features, rather than altered local mechanisms.