No Evidence of Cross-Orientation Suppression Differences in Migraine with Aura Compared to Healthy Controls.

It has been suggested that there may be an imbalance of excitation and inhibitory processes in the visual areas of the brain in people with migraine aura (MA). One idea is thalamocortical dysrhythmia, characterized by disordered oscillations, and thus disordered communication between the lateral geniculate nucleus and the cortex. Cross-orientation suppression is a visual task thought to rely on inhibitory processing, possibly originating in the lateral geniculate nucleus. We measured both resting-state oscillations and cross-orientation suppression using EEG over occipital areas in people with MA and healthy volunteers. We found evidence of cross-orientation suppression in the SSVEP responses, but no evidence of any group difference. Therefore, inhibitory processes related to cross-orientation suppression do not appear to be impaired in MA.

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.

Effect of temporal frequency on habituation in migraine.

Individuals with migraine tend to experience discomfort when viewing flickering stimuli. It has been suggested that one of the characteristics of migraine is a lack of habituation to repetitive visual stimuli, although findings can be mixed. Previous work has typically used similar visual stimuli (chequerboard) and only one temporal frequency. This study systematically varied the spatial and temporal characteristics of the visual stimulus, using steady-state visual evoked potentials to assess the differences in amplitude between migraine and control group over consecutive blocks of stimulation. Twenty individuals with migraine and 18 control observers were asked to rate their visual discomfort after viewing sequences of flickering Gabor patches with a frequency of either 3 or 9 Hz across three different spatial frequencies (low 0.5 cpd; mid-range 3 cpd; high 12 cpd). Compared to the control group, the migraine group showed a reduction in SSVEP responses with increased exposure, suggesting habituation processes are intact at 3-Hz stimulation. However, at 9-Hz stimulation, there was evidence of increased responses with increasing exposure in the migraine group in particular, which might suggest a build-up of the response over repetitive presentations. Visual discomfort varied with spatial frequency, for both 3- and 9-Hz stimuli, the highest spatial frequencies were the least uncomfortable compared to the low- and mid-range spatial frequencies in both groups. This difference in SSVEP response behaviour, dependent on temporal frequency, is important to consider when researching the effects of repetitive visual stimulation in migraine and could give some indication of build-up of effects leading to aversion to visual stimuli.

A comparison of equivalent noise methods in investigating local and global form and motion integration.

Static and dynamic cues within certain spatiotemporal proximity are used to evoke respective global percepts of form and motion. The limiting factors in this process are, first, internal noise, which indexes local orientation/direction detection, and, second, sampling efficiency, which relates to the processing and the representation of global orientation/direction. These parameters are quantified using the equivalent noise (EN) paradigm. EN has been implemented with just two levels: high and low noise. However, when using this simplified version, one must assume the shape of the overall noise dependence, as the intermediate points are missing. Here, we investigated whether two distinct EN methods, the 8-point and the simplified 2-point version, reveal comparable parameter estimates. This was performed for three different types of stimuli: random dot kinematograms, and static and dynamic translational Glass patterns, to investigate how constant internal noise estimates are, and how sampling efficiency might vary over tasks. The results indicated substantial compatibility between estimates over a wide range of external noise levels sampled with eight data points, and a simplified version producing two highly informative data points. Our findings support the use of a simplified procedure to estimate essential form-motion integration parameters, paving the way for rapid and critical applications to populations that cannot tolerate protracted measurements.

The relationship between visual discomfort and cortical excitability in cone-opponent stimuli.

Increased colour contrast can induce visual discomfort, but there is little research on the effect of hue. Colour is processed via one or more information streams or channels. We hypothesized that hues which activate more than one channel would induce greater visual discomfort, as they will demand greater neural resources. Normally-sighted young observers made discomfort judgments of isoluminant stimuli of varying hue and contrast whilst EEG was recorded. As predicted, stimuli recruiting more than one channel were more uncomfortable, and this increased with contrast. Uncomfortable stimuli showed increased N2 event-related potentials and decreased alpha-band oscillations, potentially indicating increased neural excitability. This is evidence that increased neural responses are related to visual discomfort for chromatic stimuli. Furthermore, it suggests that the origins of visual discomfort are in early visual areas, when colour is represented in a cone-opponent space, rather than later areas where colour representation is determined by perceptual similarity.

Steady-state visual evoked potential responses predict visual discomfort judgements.

It has been suggested that aesthetically pleasing stimuli are processed efficiently by the visual system, whereas uncomfortable stimuli are processed inefficiently. This study consists of a series of three experiments investigating this idea using a range of images of abstract artworks, photographs of natural scenes, and computer-generated stimuli previously shown to be uncomfortable. Subjective judgements and neural correlates were measured using electroencephalogram (EEG) (steady-state visual evoked potentials, SSVEPs). In addition, global image statistics (contrast, Fourier amplitude spectral slope and fractal dimension) were taken into account. When effects of physical image contrast were controlled, fractal dimension predicted discomfort judgements, suggesting the SSVEP response is more likely to be influenced by distribution of edges than the spectral slope. Importantly, when effects of physical contrast and fractal dimension were accounted for using linear mixed effects modelling, SSVEP responses predicted subjective judgements of images. Specifically, when stimuli were not matched for perceived contrast, there was a positive relationship between SSVEP responses and how pleasing a stimulus was judged to be, and conversely a negative relationship between discomfort and SSVEP response. This is significant as it shows that the neural responses in early visual areas contribute to the subjective (un)pleasantness of images, although the results of this study do not provide clear support for the theory of efficient coding as the cause of perceived pleasantness or discomfort of images, and so other explanations need to be considered.

Improvement in visual perception after high-frequency transcranial random noise stimulation (hf-tRNS) in those with migraine: An equivalent noise approach.

Migraine is a common neurological disorder with strong links to vision. Interictal migraine is thought to be characterised by internal noise in the brain, possibly due to increased variability in neural firing, which can be estimated using equivalent noise tasks. High-frequency transcranial random noise stimulation (hf-tRNS) can be used to modulate levels of internal noise in the brain, and so presents a possible therapy to redress noise levels in the migraine brain. This is a case-control study using a 2-alternative forced choice (2AFC) design. Hf-tRNS and Sham control stimulation were used alongside a global motion direction discrimination task and visually based equivalent noise tasks. The migraine group demonstrated increased baseline internal noise levels compared to the control group. Internal noise levels, and sampling, were reduced using hf-tRNS but not Sham stimulation. However, there were no differences in terms of coherence thresholds, slopes, and lapse rate for global motion discrimination between the two groups. This is the first demonstration of the possibility of decreasing internal noise levels in migraine using hf-tRNS. Future work could explore the possibility of neurostimulation as a therapy for migraine.

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 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.

Electrophysiological aftereffects of high-frequency transcranial random noise stimulation (hf-tRNS): an EEG investigation.

There is evidence that high-frequency transcranial random noise stimulation (hf-tRNS) is effective in improving behavioural performance in several visual tasks. However, so far there has been limited research into the spatial and temporal characteristics of hf-tRNS-induced facilitatory effects. In the present study, electroencephalogram (EEG) was used to investigate the spatial and temporal dynamics of cortical activity modulated by offline hf-tRNS on performance on a motion direction discrimination task. We used EEG to measure the amplitude of motion-related VEPs over the parieto-occipital cortex, as well as oscillatory power spectral density (PSD) at rest. A time-frequency decomposition analysis was also performed to investigate the shift in event-related spectral perturbation (ERSP) in response to the motion stimuli between the pre- and post-stimulation period. The results showed that the accuracy of the motion direction discrimination task was not modulated by offline hf-tRNS. Although the motion task was able to elicit motion-dependent VEP components (P1, N2, and P2), none of them showed any significant change between pre- and post-stimulation. We also found a time-dependent increase of the PSD in alpha and beta bands regardless of the stimulation protocol. Finally, time-frequency analysis showed a modulation of ERSP power in the hf-tRNS condition for gamma activity when compared to pre-stimulation periods and Sham stimulation. Overall, these results show that offline hf-tRNS may induce moderate aftereffects in brain oscillatory activity.

The Effect of Motion Direction and Eccentricity on Vection, VR Sickness and Head Movements in Virtual Reality.

Virtual Reality (VR) experienced through head-mounted displays often leads to vection, discomfort and sway in the user. This study investigated the effect of motion direction and eccentricity on these three phenomena using optic flow patterns displayed using the Valve Index. Visual motion stimuli were presented in the centre, periphery or far periphery and moved either in depth (back and forth) or laterally (left and right). Overall vection was stronger for motion in depth compared to lateral motion. Additionally, eccentricity primarily affected stimuli moving in depth with stronger vection for more peripherally presented motion patterns compared to more central ones. Motion direction affected the various aspects of VR sickness differently and modulated the effect of eccentricity on VR sickness. For stimuli moving in depth far peripheral presentation caused more discomfort, whereas for lateral motion the central stimuli caused more discomfort. Stimuli moving in depth led to more head movements in the anterior-posterior direction when the entire visual field was stimulated. Observers demonstrated more head movements in the anterior-posterior direction compared to the medio-lateral direction throughout the entire experiment independent of motion direction or eccentricity of the presented moving stimulus. Head movements were elicited on the same plane as the moving stimulus only for stimuli moving in depth covering the entire visual field. A correlation showed a positive relationship between dizziness and vection duration and between general discomfort and sway. Identifying where in the visual field motion presented to an individual causes the least amount of VR sickness without losing vection and presence can guide development for Virtual Reality games, training and treatment programmes.

Resting-State Alpha-Band Oscillations in Migraine.

Migraine groups show differences in motion perception compared with controls, when tested in between migraine attacks (interictally). This is thought to be due to an increased susceptibility to stimulus degradation (multiplicative internal noise). Fluctuations in alpha-band oscillations are thought to regulate visual perception, and so differences could provide a mechanism for the increased multiplicative noise seen in migraine. The aim of this article was to characterise resting-state alpha-band oscillations (between 8 and 12 Hz) in the visual areas of the brain in migraine and control groups. Alpha-band activity in the resting state (with eyes closed) was recorded before and after a visual psychophysics task to estimate equivalent noise, specifically a contrast detection task. The lower alpha-band (8 to 10 Hz) resting-state alpha-band power was increased in the migraine compared with the control group, which may provide a mechanism for increased multiplicative noise. In agreement with previous research, there were no differences found in the additive (baseline) internal noise, estimated using an equivalent noise task in the same observers. As fluctuations in alpha-band oscillations control the timing of perceptual processing, increased lower alpha-band (8 to 10 Hz) power could explain the behavioural differences in migraine compared with control groups, particularly on tasks relying on temporal integration.

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.

Temporal Integration of Motion Streaks in Migraine.

Migraine is associated with differences in visual perception, specifically, deficits in the perception of motion. Migraine groups commonly show poorer performance (higher thresholds) on global motion tasks compared to control groups. Successful performance on a global motion task depends on several factors, including integrating signals over time. A "motion streak" task was used to investigate specifically integration over time in migraine and control groups. The motion streak effect depends on the integration of a moving point over time to create the illusion of a line, or "streak". There was evidence of a slower optimum speed for eliciting the motion streak effect in migraine compared to control groups, suggesting temporal integration is different in migraine. In addition, performance on the motion streak task showed a relationship with headache frequency.

Investigating Head Movements Induced by 'Riloid' Patterns in Migraine and Control Groups Using a Virtual Reality Display.

Certain striped patterns can induce illusory motion, such as those used in op-art. The visual system and the vestibular system work together closely, and so it is possible that illusory motion from a visual stimulus can result in uncertainty in the vestibular system. This increased uncertainty may be measureable in terms of the magnitude of head movements. Head movements were measured using a head-mounted visual display. Results showed that stimuli associated with illusory motion also seem to induce greater head movements when compared to similar stimuli. Individuals with migraine are more susceptible to visual discomfort, and this includes illusory motion from striped stimuli. However, there was no evidence of increased effect of illusory motion on those with migraine compared to those without, suggesting that while motion illusions may affect discomfort judgements, this is not limited to only those with migraine.

Frail older adults' perceptions of an in-hospital structured exercise intervention.

BACKGROUND: Exercise interventions need to be assessed qualitatively to establish how people participate in and perceive the intervention and how interventions should be delivered for maximal effect. OBJECTIVES: To explore how frail older inpatients perceived the effects of a pilot augmented prescribed exercise programme (APEP). DESIGN: An interpretive phenomenological design using open-ended semi-structured interviews. Data were analysed using thematic content analysis. SETTING: An acute teaching hospital. PARTICIPANTS: Thirteen of the frail older adults who participated in the APEP. RESULTS: The participants' perceived relationship with the interventionist was highly influential, affecting participation rates, perceived value of the APEP, and outcome expectations. Pre-existing positive outcome expectations increased the likelihood of fully engaging in the programme and valuing the outcomes. Barriers to the intervention included negative or no outcome expectations and fatalism. Recent exercise history affected their views of the APEP. Perceived positive outcomes included increased intention to exercise postdischarge, improved self-efficacy and perceived improvements in physical status. CONCLUSION: Exercise interventions targeting frail older adults in the acute setting may benefit from taking a multifaceted approach to implementation. Education tailored to the participants, and setting restorative goals, may improve outcome expectations and future intention to exercise. The relationship between the participants and those implementing an intervention appears critical to their participation and whether they value the programme.

Multisensory Integration in Migraine: Recent Developments.

There are well-documented unimodal sensory differences in migraine compared to control groups both during, and between migraine attacks. There is also some evidence of multisensory integration differences in migraine groups compared to control groups, however the literature on this topic is more limited. There are interesting avenues in the area of visual-vestibular integration, which might have practical implications, e.g., motion sickness and nausea in migraine. Recent work has been investigating the possibility of visual-auditory integration in migraine, and found possible differences in the susceptibility to the sound-induced flash illusion in particular, which could give insights into relative excitability of different areas of the cortex, and also into mechanisms for the illusions themselves. This review updates the most recent literature and also highlights potentially fruitful areas of research to understand one of the most common neurological disorders.

Visual Discomfort From Flash Afterimages of Riloid Patterns.

Op-art-based stimuli have been shown to be uncomfortable, possibly due to a combination of fixational eye movements (microsaccades) and excessive cortical responses. Efforts have been made to measure illusory phenomena arising from these stimuli in the absence of microsaccades, but there has been no attempt thus far to decouple the effects of the cortical response from the effect of fixational eye movements. This study uses flash afterimages to stabilise the image on the retina and thus reduce the systematic effect of eye movements, in order to investigate the role of the brain in discomfort from op-art-based stimuli. There was a relationship between spatial frequency and the magnitude of the P300 response, showing a similar pattern to that of discomfort judgements, which suggests that there might be a role of discomfort and excessive neural responses independently from the effects of microsaccades.

Steady-state VEP responses to uncomfortable stimuli.

Periodic stimuli, such as op-art, can evoke a range of aversive sensations included in the term visual discomfort. Illusory motion effects are elicited by fixational eye movements, but the cortex might also contribute to effects of discomfort. To investigate this possibility, steady-state visually evoked responses (SSVEPs) to contrast-matched op-art-based stimuli were measured at the same time as discomfort judgements. On average, discomfort reduced with increasing spatial frequency of the pattern. In contrast, the peak amplitude of the SSVEP response was around the midrange spatial frequencies. Like the discomfort judgements, SSVEP responses to the highest spatial frequencies were lowest amplitude, but the relationship breaks down between discomfort and SSVEP for the lower spatial frequency stimuli. This was not explicable by gross eye movements as measured using the facial electrodes. There was a weak relationship between the peak SSVEP responses and discomfort judgements for some stimuli, suggesting that discomfort can be explained in part by electrophysiological responses measured at the level of the cortex. However, there is a breakdown of this relationship in the case of lower spatial frequency stimuli, which remains unexplained.

Causal Role of Thalamic Interneurons in Brain State Transitions: A Study Using a Neural Mass Model Implementing Synaptic Kinetics.

Experimental studies on the Lateral Geniculate Nucleus (LGN) of mammals and rodents show that the inhibitory interneurons (IN) receive around 47.1% of their afferents from the retinal spiking neurons, and constitute around 20-25% of the LGN cell population. However, there is a definite gap in knowledge about the role and impact of IN on thalamocortical dynamics in both experimental and model-based research. We use a neural mass computational model of the LGN with three neural populations viz. IN, thalamocortical relay (TCR), thalamic reticular nucleus (TRN), to study the causality of IN on LGN oscillations and state-transitions. The synaptic information transmission in the model is implemented with kinetic modeling, facilitating the linking of low-level cellular attributes with high-level population dynamics. The model is parameterized and tuned to simulate alpha (8-13 Hz) rhythm that is dominant in both Local Field Potential (LFP) of LGN and electroencephalogram (EEG) of visual cortex in an awake resting state with eyes closed. The results show that: First, the response of the TRN is suppressed in the presence of IN in the circuit; disconnecting the IN from the circuit effects a dramatic change in the model output, displaying high amplitude synchronous oscillations within the alpha band in both TCR and TRN. These observations conform to experimental reports implicating the IN as the primary inhibitory modulator of LGN dynamics in a cognitive state, and that reduced cognition is achieved by suppressing the TRN response. Second, the model validates steady state visually evoked potential response in humans corresponding to periodic input stimuli; however, when the IN is disconnected from the circuit, the output power spectra do not reflect the input frequency. This agrees with experimental reports underpinning the role of IN in efficient retino-geniculate information transmission. Third, a smooth transition from alpha to theta band is observed by progressive decrease of neurotransmitter concentrations in the synaptic clefts; however, the transition is abrupt with removal of the IN circuitry in the model. The results imply a role of IN toward maintaining homeostasis in the LGN by suppressing any instability that may arise due to anomalous synaptic attributes.