fMRI studies of amblyopia: Pediatric and adult perspectives

Functional magnetic resonance imaging (fMRI) is currently the technique of choice for mapping functional neuroanatomy in humans, and over the past 15 years there has been a dramatic growth in the number of studies that provide brain-behavior correlations in normal healthy adults. More recently, a few studies have begun to make such measures in healthy children. In addition, fMRI is increasingly being applied to study brain function in subjects with neurological disease. The overall aim of these studies was to apply fMRI methods to the study of amblyopia, the most prevalent developmental vision disorder. Amblyopia develops early in life, usually before 5 years old, and is most treatable during childhood. Our approach was to study both children and adults with either the strabismic or the anisometropic type of amblyopia. In our first experiment (Chapter 3), we applied fMRI techniques to map retinotopic visual organization in children. We conclude that cortical visual organization is measurable and highly mature in children aged 9 to 12 years. In our second experiment (Chapter 4), we applied similar techniques to adults with amblyopia. We conclude that visual field organization is abnormal in the brains of these adults. In our final experiment (Chapter 5), we applied these same techniques to children with amblyopia, and observed abnormalities similar to those seen in adults. These studies present a novel neurological characterization of amblyopia, and provide a basis for further studies of human visual development, in health and disease

Using magnetic resonance imaging to assess visual deficits : a review

PURPOSE: Over the last two decades, magnetic resonance imaging (MRI) has been widely used in neuroscience research to assess both structure and function in the brain in health and disease. With regard to vision research, prior to the advent of MRI, researchers relied on animal physiology and human post-mortem work to assess the impact of eye disease on visual cortex and connecting structures. Using MRI, researchers can non-invasively examine the effects of eye disease on the whole visual pathway, including the lateral geniculate nucleus, striate and extrastriate cortex. This review aims to summarise research using MRI to investigate structural, chemical and functional effects of eye diseases, including: macular degeneration, retinitis pigmentosa, glaucoma, albinism, and amblyopia. RECENT FINDINGS: Structural MRI has demonstrated significant abnormalities within both grey and white matter densities across both visual and non-visual areas. Functional MRI studies have also provided extensive evidence of functional changes throughout the whole of the visual pathway following visual loss, particularly in amblyopia. MR spectroscopy techniques have also revealed several abnormalities in metabolite concentrations in both glaucoma and age-related macular degeneration. GABA-edited MR spectroscopy on the other hand has identified possible evidence of plasticity within visual cortex. SUMMARY: Collectively, using MRI to investigate the effects on the visual pathway following disease and dysfunction has revealed a rich pattern of results allowing for better characterisation of disease. In the future MRI will likely play an important role in assessing the impact of eye disease on the visual pathway and how it progresses over time

Estimation of cortical magnification from positional error in normally sighted and amblyopic subjects

yesWe describe a method for deriving the linear cortical magnification factor from positional error across the visual field. We compared magnification obtained from this method between normally sighted individuals and amblyopic individuals, who receive atypical visual input during development. The cortical magnification factor was derived for each subject from positional error at 32 locations in the visual field, using an established model of conformal mapping between retinal and cortical coordinates. Magnification of the normally sighted group matched estimates from previous physiological and neuroimaging studies in humans, confirming the validity of the approach. The estimate of magnification for the amblyopic group was significantly lower than the normal group: by 4.4 mm deg 1 at 18 eccentricity, assuming a constant scaling factor for both groups. These estimates, if correct, suggest a role for early visual experience in establishing retinotopic mapping in cortex. We discuss the implications of altered cortical magnification for cortical size, and consider other neural changes that may account for the amblyopic results

Neuroimaging of amblyopia and binocular vision: a review

Amblyopia is a cerebral visual impairment considered to derive from abnormal visual experience (e.g., strabismus, anisometropia). Amblyopia, first considered as a monocular disorder, is now often seen as a primarily binocular disorder resulting in more and more studies examining the binocular deficits in the patients. The neural mechanisms of amblyopia are not completely understood even though they have been investigated with electrophysiological recordings in animal models and more recently with neuroimaging techniques in humans. In this review, we summarize the current knowledge about the brain regions that underlie the visual deficits associated with amblyopia with a focus on binocular vision using functional magnetic resonance imaging. The first studies focused on abnormal responses in the primary and secondary visual areas whereas recent evidence shows that there are also deficits at higher levels of the visual pathways within the parieto-occipital and temporal cortices. These higher level areas are part of the cortical network involved in 3D vision from binocular cues. Therefore, reduced responses in these areas could be related to the impaired binocular vision in amblyopic patients. Promising new binocular treatments might at least partially correct the activation in these areas. Future neuroimaging experiments could help to characterize the brain response changes associated with these treatments and help devise them

Neuroimaging of binocular vision in human amblyopia

Amblyopia is a visual developmental condition that usually occurs when one eye receives abnormal input. For many years amblyopia was thought to be untreatable beyond 8 years old, after which the visual system would become functionally monocular. Recent research has shown that binocular mechanisms do remain intact in amblyopia and therefore investigating the nature of the deficit is crucial for understanding where neural problems arise and how they can be treated. Chapter 3 used population receptive field (pRF) modelling to further understand the cortical problems caused by amblyopia. Findings suggest that neurons responding to the amblyopic eye have reduced spatial resolution within striate and extrastriate areas. Chapters 4 and 5 aimed to test the predictions of different computational models of amblyopia using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), within the same group of participants. This is the first study to use a model driven approach to directly compare both neuroimaging methods within the same participants. The pattern of fMRI responses from the amblyopic eye showed evidence of a response gain effect and unbalanced interocular suppression, whereas EEG responses showed evidence of a contrast gain shift. Finally, Chapter 6 used EEG to objectively measure visual improvements, following treatment for amblyopia in children and adults. Measurable steady-state EEG responses were found for both groups; however, there was no convincing evidence of improvements in amblyopic eye responses throughout treatment. The studies undertaken in this thesis contribute to the wider understanding of the neural basis of amblyopia. Two different neuroimaging methods are compared, which has enabled insight into how current computational models of amblyopia could be improved. It is hoped that this research will further the development of treatments for amblyopia, by providing more insight into how binocular visual processes break down between the eyes

Amblyopic deficit beyond the fovea : delayed and variable single-trial ERP response latencies, but unaltered amplitudes

Purpose. Amblyopia was first described as a deficit of central vision. However, it has long been debated whether this dysfunction is limited to the fovea or whether extrafoveal vision is also affected, as studies concerning the latter are equivocal. The purpose of the study was to resolve this issue. Methods. We investigated the amblyopic effect on event-related potentials (ERPs) with foveal and perifoveal stimuli, either matched in size based on cortical magnification or presented as large annular stimuli. In two separate experiments we measured ERPs on amblyopic patients and control subjects using face images. Latency and amplitude of averaged ERPs and their single-trial distributions were analyzed. Results. When the fovea was stimulated, latency and amplitude of the early averaged ERP components increased and were reduced, respectively, in the amblyopic compared with the fellow eye. Importantly, perifoveal stimulation also elicited similar amblyopic deficits, which were clearly significant in the case of using cortical magnification scaled stimuli. However, single-trial peak analysis revealed that foveal and perifoveal effects differed in nature: Peak amplitudes were reduced only in foveal stimulation, while latencies were delayed and jittered at both the fovea and perifovea. Event-related potentials obtained from fellow eyes were not significantly different from those of normal observers. Conclusions. Our findings revealed the existence of amblyopic deficits at the perifovea when the stimulated cortical area was matched in size to that of foveal stimulation. These deficits manifested themselves only in the temporal structure of the responses, unlike foveal deficits, which affected both component amplitude and latency

Strabismic amblyopes show a bilateral rightward bias in a line bisection task: Evidence for a visual attention deficit

AbstractNeurologically normal observers show a consistent leftward bias when asked to bisect a horizontal line (“pseudoneglect”). In this study, we found that subjects with strabismic and strabismic-anisometropic amblyopia show a consistent rightward bias (“minineglect”) in a line bisection task. The bias was seen in both eyes, but affected more strongly the amblyopic eye. Purely anisometropic amblyopes show a similar bias, affecting only the amblyopic eye. The group of strabismics with alternating fixation did not differ significantly from normal observers. These errors are reminiscent of the attentional neglect of the left extrapersonal space, shown by subjects with lesions in the right posterior parietal cortex. We suggest that an early strabismus might lead to a functional deficit of the dorsal cortical pathway, in addition to the well-known impairments on the ventral visual pathway. We conclude that strabismic amblyopes might show subtle attentional deficits, in addition to their unilateral vision loss

Current Trends of fMRI in Vision Science: A Review

Studying brain functional activities is an area that is experiencing rapid interest in the field of neuroimaging. Functional magnetic resonance imaging (fMRI) has provided vision science researchers a powerful and noninvasive tool to understand eye function and correlate it with brain activities. In this chapter, we focus on the physiological aspects followed by a literature review. More specifically, to motivate and appreciate the complexity of the visual system, we will begin with a description of specific stages the visual pathway, beginning from the distal stimulus and ending in the visual cortex. More importantly, the development of ascending visual pathway will be discussed in order to help in understanding various disorders associated with it such as monochromacy, albinism, amblyopia (refractive, strabismic). In doing so we will divide the first half into two main sections, the visual pathway and the development of the ascending pathway. The first of these sections will be mostly an anatomy review and the latter will discuss the development of this anatomy with specific examples of disorders as a result of abnormal development. We will then discuss fMRI studies with focus on vision science applications. The remaining sections of this chapter will be highlighting the work done on mainly oculomotor function, some perception and visual dysfunction with fMRI and investigate the differences and similarities in their findings. We will then conclude with a discussion on how this relates to neurologists, neuroscientists, ophthalmologists and other specialists

Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD

Sensory deprivation during the post-natal 'critical period' leads to structural reorganization of the developing visual cortex. In adulthood, the visual cortex retains some flexibility and adapts to sensory deprivation. Here we show that short-term (2 hr) monocular deprivation in adult humans boosts the BOLD response to the deprived eye, changing ocular dominance of V1 vertices, consistent with homeostatic plasticity. The boost is strongest in V1, present in V2, V3 and V4 but absent in V3a and hMT+. Assessment of spatial frequency tuning in V1 by a population Receptive-Field technique shows that deprivation primarily boosts high spatial frequencies, consistent with a primary involvement of the parvocellular pathway. Crucially, the V1 deprivation effect correlates across participants with the perceptual increase of the deprived eye dominance assessed with binocular rivalry, suggesting a common origin. Our results demonstrate that visual cortex, particularly the ventral pathway, retains a high potential for homeostatic plasticity in the human adult

Structural Integrity of Eyes Diagnosed with Amblyopia. The measurement of retinal structure in amblyopia using Optical Coherence Tomography.

Amblyopia is the leading cause of monocular visual impairment in children. Therapy for amblyopia is extremely beneficial in some children but ineffective in others. It is critical that the reasons for this discrepancy are understood. Emerging evidence indicates that current clinical protocols for the diagnosis of amblyopia may not be sufficiently sensitive in identifying individuals who, on more detailed examination, exhibit subtle structural defects of the eye. Presently, the magnitude of this problem is unknown. The aim of this study was to establish the prevalence of subtle retinal/optic nerve head defects in eyes diagnosed with amblyopia, to distinguish between possible explanations for the origin of such defects and to investigate the relationship between quantitative measures of retinal structure, retinal nerve fibre layer thickness and optic nerve head dimensions. Using the imaging technique of Optical Coherence Tomography (OCT) retinal structure has been investigated in detail, following the visual pathway across the retina from the fovea, via the paramacular bundle to the optic disc, where peripapillary retinal nerve fibre thickness has been imaged and subjected to detailed measures along with optic disc size and shape. The study formed two phases, the first imaging the eyes of visually normal adults and children, comparing them to amblyopes, both adults and children who had completed their treatment. The second phase, a longitudinal study, investigated retinal structure of amblyopic children undertaking occlusion therapy for the first time. By relating pre-therapy quantitative measures to the visual outcome the second phase of the study aimed to examine whether OCT imaging could identify children achieving a poor final outcome. The results show a clear picture of inter-ocular symmetry structure in all individuals, visually normal and amblyopic. Optic disc characteristics revealed no structural abnormalities in amblyopes, in any of the measured parameters, nor was there any association between the level of visual acuity and the measured structure. At the fovea differences were shown to occur in the presence of amblyopia, with thickening of the fovea and reduction of the foveal pit depth. The structural changes were found to be both bilateral and symmetrical with the fellow eye also affected. In the longitudinal phase of the study these changes were demonstrated to a greater extent in children who ¿failed¿ to respond to treatment. This bilateral, symmetrical structural change found at the fovea, which has not been previously reported, cannot therefore be the primary cause of the visual loss which has been diagnosed as amblyopia