Bao N. Nguyen

The effect of duration post-migraine on visual electrophysiology and visual field performance in people with migraine.

Purpose: In between migraine attacks, some people show visual field defects that are worse when measured closer to the end of a migraine event. In this cohort study, we consider whether electrophysiological responses correlate with visual field performance at different times post-migraine, and explore evidence for cortical versus retinal origin. Methods: Twenty-six non-headache controls and 17 people with migraine performed three types of perimetry (static, flicker and blue-on-yellow) to assess different aspects of visual function at two visits conducted at different durations post-migraine. On the same days, the pattern electroretinogram (PERG) and visual evoked response (PVER) were recorded. Results: Migraine participants showed persistent, interictal, localised visual field loss, with greater deficits at the visit nearer to migraine offset. Spatial patterns of visual field defect consistent with retinal and cortical dysfunction were identified. The PERG was normal, whereas the PVER abnormality found did not change with time post-migraine and did not correlate with abnormal visual field performance. Conclusions: Dysfunction on clinical tests of vision is common in between migraine attacks; however, the nature of the defect varies between individuals and can change with time. People with migraine show markers of both retinal and/or cortical dysfunction. Abnormal visual field sensitivity does not predict abnormality on electrophysiological testing.

Simultaneous retinal and cortical visually evoked electrophysiological responses in between migraine attacks

Purpose: People with migraine often report aversion to flickering lights and show abnormal results on behavioural tasks that require the processing of temporal visual information. Studies have reported that the cortically evoked electrophysiological response to a flickering visual stimulus is abnormal; however, none have considered whether there is an underlying pre-cortical abnormality. In this cross-sectional study, we consider whether people with migraine have retinal and cortical electrophysiological abnormalities to flickering stimuli. Methods: Monocular transient (1 Hz) and steady-state (8.3 Hz) pattern reversal electroretinograms (PERGs) and pattern visual evoked responses (PVERs) were measured simultaneously in 45 people with migraine (26 without aura, 19 with aura) and 30 non-headache controls at a time between migraine attacks. Results: PERG amplitude and timing did not differ significantly between groups. Transient PVER amplitude was significantly reduced (28%) in the migraine with aura group compared to the controls F(2,72) = 3.6, p = 0.03). Both migraine groups showed significant reductions (32%, 39%) in steady-state PVER amplitude relative to controls (F(2,70) = 4.3, p = 0.02). Conclusions: This study finds normal retinal processing of flickering stimuli in the presence of abnormal cortical function between migraine attacks.

Foveal and parafoveal contrast suppression are different: Mechanisms revealed by the study of healthy aging.

Visual contextual effects enable inference regarding neural mechanisms of cortical function, principally because of similarities between the stimulus properties influencing human perception and those modifying primate visual cortical neural responses. Most neurophysiology assesses nonfoveal cellular function and circuitry, while most human studies are foveal. Here we use parafoveal stimuli to measure center-surround perception of contrast in older and younger adults. We measure the influence of both near and far surround because neurophysiology demonstrates different circuitry for these areas. Contrast suppression from the near surround was reduced in older observers, while that from the far surround was intact. Our results are consistent with reduced intracortical inhibition with age and normal extrastriate feedback. Interestingly, in the same older observers, foveal surround suppression of contrast was strengthened relative to younger adults, demonstrating a clear distinction between foveal and parafoveal center-surround behavior. We assume that underlying alterations in cortical neurotransmitter levels with age should not differ substantially between the areas of visual cortex representing foveal and near foveal regions. Consequently, our results suggest regional differences in center-surround circuitry. That older adults have varied contextual effects of visual contrast as a function of retinal eccentricity suggests complex effects of aging on scene and object perception.

Visual Contextual Effects of Orientation, Contrast, Flicker, and Luminance: All Are Affected by Normal Aging.

The perception of a visual stimulus can be markedly altered by spatial interactions between the stimulus and its surround. For example, a grating stimulus appears lower in contrast when surrounded by a similar pattern of higher contrast: a phenomenon known as surround suppression of perceived contrast. Such center–surround interactions in visual perception are numerous and arise from both cortical and pre-cortical neural circuitry. For example, perceptual surround suppression of luminance and flicker are predominantly mediated pre-cortically, whereas contrast and orientation suppression have strong cortical contributions. Here, we compare the perception of older and younger observers on a battery of tasks designed to assess such visual contextual effects. For all visual dimensions tested (luminance, flicker, contrast, and orientation), on average the older adults showed greater suppression of central targets than the younger adult group. The increase in suppression was consistent in magnitude across all tasks, suggesting that normal aging produces a generalized, non-specific alteration to contextual processing in vision.

Abnormal inhibition-excitation imbalance in migraine.

Background People with migraine show increased surround suppression of perceived contrast, a perceptual analogue of centre-surround antagonistic interactions in visual cortex. A proposed mechanism is that cortical ‘hyperexcitability’ or ‘hyperresponsivity’, a prominent theory in the migraine literature, drives abnormal excitatory-inhibitory balance to give increased local inhibition. The purpose of this cross-sectional study was to determine whether cortical hyperresponsivity and excitatory-inhibitory imbalance manifests in the visual cortical response of migraine sufferers. Methods Interictal steady-state visual evoked potentials (VEPs) in response to 0 to 97% contrast were recorded in 30 migraine participants (15 without aura, 15 with aura) and 21 non-headache controls. Monotonicity indices were calculated to determine response saturation or supersaturation. Contrast gain was modelled with a modified saturating hyperbolic function to allow for variation in excitation and inhibition. Results A greater proportion of migraine participants (43%) than controls (14%) exhibited significant VEP supersaturation at high contrast, based on monotonicity index (chi-square, p = 0.028). Supersaturation was also evident by the trend for greater suppressive exponent values in migraine compared to control individuals (Mann-Whitney rank sum, p = 0.075). Conclusions Supersaturation in migraine is consistent with excess excitation (hyperresponsivity) driving increased network inhibition and provides support for excitatory-inhibitory imbalance as a pathophysiological disturbance in migraine.

Clinical impact of migraine for the management of glaucoma patients.

Migraine is a common and debilitating primary headache disorder that affects 10-15% of the general population, particularly people of working age. Migraine is relevant to providers of clinical eye-care because migraine attacks are associated with a range of visual sensory symptoms, and because of growing evidence that the results of standard tests of visual function necessary for the diagnosis and monitoring of glaucoma (visual fields, electrophysiology, ocular imaging) can be abnormal due to migraine. These abnormalities are measureable in-between migraine events (the interictal period), despite patients being asymptomatic and otherwise healthy. This picture is further complicated by epidemiological data that suggests an increased prevalence of migraine in patients with glaucoma, particularly in patients with normal tension glaucoma. We discuss how migraine, as a co-morbidity, can confound the results and interpretation of clinical tests that form part of contemporary glaucoma evaluation, and provide practical evidence-based recommendations for the clinical testing and management of patients with migraine who attend eye-care settings.

Occipital GABA levels in older adults and their relationship to visual perceptual suppression

Several studies have attributed certain visual perceptual alterations in older adults to a likely decrease in GABA (Gamma Aminobutyric Acid) concentration in visual cortex, an assumption based on findings in aged non-human primates. However, to our knowledge, there is no direct evidence for an age-related decrease in GABA concentration in human visual cortex. Here, we estimated visual cortical GABA levels and Glx (combined estimate of glutamate and glutamine) levels using magnetic resonance spectroscopy. We also measured performance for two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion and binocular rivalry. Our results show increased visual cortical GABA levels, and reduced Glx levels, in older adults. Perceptual performance differed between younger and older groups for both tasks. When subjects of all ages were combined, visual cortical GABA levels but not Glx levels correlated with perceptual performance. No relationship was found between perception and GABA levels in dorsolateral prefrontal cortex. Perceptual measures and GABA were not correlated when either age group was considered separately. Our results challenge current assumptions regarding neurobiological changes that occur within the aging human visual cortex and their association with certain age-related changes in visual perception.

Orientation of the Temporal Nerve Fiber Raphe in Healthy and in Glaucomatous Eyes

Purpose To determine the normal variation in orientation of the temporal nerve fiber raphe, and the accuracy with which it may be predicted or approximated in lieu of direct measurement. Methods We previously described an algorithm for automatic measurement of raphe orientation from optical coherence tomography, using the intensity of vertically oriented macular cubes. Here this method was applied in 49 healthy participants (age 19-81 years) and 51 participants with primary open angle glaucoma (age 51-80 years). Results Mean fovea-disc-raphe angle was 173.5° ± 3.2° (range = 166°-182°) and 174.2° ± 3.4° (range = 166°-184°) in healthy and glaucoma patients, respectively. Differences between groups were not significant. Fovea-disc-raphe angle was not correlated with age or axial length (P > 0.4), showed some symmetry between eyes in glaucoma (R2 = 0.31, P < 0.001), and little symmetry in the healthy group (P = 0.06). Fovea-disc angle was correlated with fovea-raphe angle (R2 = 0.27, P = 0.0001), but was not a good predictor for raphe orientation (average error = 6.8°). The horizontal axis was a better predictor (average error = 3.2°; maximum error = 9.6°), but still gave approximately twice the error previously reported for direct measurement from macular cubes. Conclusions There is substantial natural variation in temporal nerve fiber raphe orientation, which cannot be predicted from age, axial length, relative geometry of the disc and fovea, or the contralateral eye. For applications to which the orientation of the raphe is considered important, it should be measured directly.

Mismatched summation mechanisms in older adults for the perception of small moving stimuli

Abstract Previous studies have found evidence for reduced cortical inhibition in aging visual cortex. Reduced inhibition could plausibly increase the spatial area of excitation in receptive fields of older observers, as weaker inhibitory processes would allow the excitatory receptive field to dominate and be psychophysically measureable over larger areas. Here, we investigated aging effects on spatial summation of motion direction using the Battenberg summation method, which aims to control the influence of locally generated internal noise changes by holding overall display size constant. This method produces more accurate estimates of summation area than conventional methods that simply increase overall stimulus dimensions. Battenberg stimuli have a checkerboard arrangement, where check size (luminance‐modulated drifting gratings alternating with mean luminance areas), but not display size, is varied and compared with performance for a full field stimulus to provide a measure of summation. Motion direction discrimination thresholds, where contrast was the dependent variable, were measured in 14 younger (24–34 years) and 14 older (62–76 years) adults. Older observers were less sensitive for all check sizes, but the relative sensitivity across sizes, also differed between groups. In the older adults, the full field stimulus offered smaller performance improvements compared to that for younger adults, specifically for the small checked Battenberg stimuli. This suggests aging impacts on short‐range summation mechanisms, potentially underpinned by larger summation areas for the perception of small moving stimuli.

Aging alters intraocular but not interocular foveal center surround contrast suppression

Numerous previous studies have shown that healthy aging results in increased foveal center surround contrast suppression when the center and surround patterns are presented to both eyes. The mechanistic cause of this observation is not well established. Neurophysiological and psychophysical studies have shown that different mechanisms of parafoveal center surround suppression can be tapped by manipulating viewing conditions to present the center and surround to the same eye (intraocular viewing) or to different eyes (interocular viewing), or by manipulating stimulus parameters such as duration. Here, we tested intraocular and interocular foveal center surround contrast suppression for stimuli of 40 ms and 200 ms duration in 18 younger and 18 older adults. For both groups, foveal intraocular center surround contrast suppression decreased with longer stimulus duration whereas interocular surround suppression did not, confirming contributions from separate mechanisms to these forms of suppression. Intraocular center surround contrast suppression was increased in older adults compared to younger adults; however, interocular suppression was similar in both groups. Our results indicate that aging differentially affects distinct forms of suppression arising at various levels of the visual pathway.