Functional and structural organisation of the visual system in human albinism

Albinism is a developmental disorder which involves the misrouting of optic nerve projections, leading to an abnormally organised visual system. Despite the aberrant input, people with albinism have relatively normal vision and experience the world in much the same way as their peers. This thesis explores the functional and structural organisation of visual cortex in human albinism using magnetic resonance imaging (MRI) techniques. This thesis covers four main experiments. Experiment 1 deals with stimulus optimisation for population receptive field (pRF) mapping in healthy adults. pRF mapping is a functional MRI technique for estimating cortical receptive field characteristics non-invasively. In this experiment, a stimulus configuration optimized for short acquisition time requirements is presented and implemented in subsequent experiments. Experiment 2 combines the pRF approach for retinotopic localization with diffusion MRI tractography in healthy adults to show evidence for direct extrastriate connections of the human optic radiation. The optic radiation is the principal white matter pathway for relaying retinal input to visual cortex, and typically considered a projection to primary visual cortex. In this experiment, independent pathways of the optic radiation to visual areas V2 and V3 are identified, and functional-structural methodologies developed for Experiment 4. Experiment 3 investigates the functional organisation of visual cortex in participants with albinism. A pRF mapping approach was implemented, identifying abnormal retinotopic organisation and altered receptive field properties in extrastriate visual cortex. In addition, we explore evidence for and against a dual receptive field model of visual field representation in albinism. Experiment 4 examines the structural and functional connectivity of early visual system in human albinism. In particular, differences in white matter microstructure and inter- hemispheric visual map connectivity are found between participants with albinism and a cohort of healthy controls. This thesis highlights the capacity and limitations of developmental plasticity in human albinism

Studying Cortical Plasticity in Ophthalmic and Neurological Disorders:From Stimulus-Driven to Cortical Circuitry Modeling Approaches

Unsolved questions in computational visual neuroscience research are whether and how neurons and their connecting cortical networks can adapt when normal vision is compromised by a neurodevelopmental disorder or damage to the visual system. This question on neuroplasticity is particularly relevant in the context of rehabilitation therapies that attempt to overcome limitations or damage, through either perceptual training or retinal and cortical implants. Studies on cortical neuroplasticity have generally made the assumption that neuronal population properties and the resulting visual field maps are stable in healthy observers. Consequently, differences in the estimates of these properties between patients and healthy observers have been taken as a straightforward indication for neuroplasticity. However, recent studies imply that the modeled neuronal properties and the cortical visual maps vary substantially within healthy participants, e.g., in response to specific stimuli or under the influence of cognitive factors such as attention. Although notable advances have been made to improve the reliability of stimulus-driven approaches, the reliance on the visual input remains a challenge for the interpretability of the obtained results. Therefore, we argue that there is an important role in the study of cortical neuroplasticity for approaches that assess intracortical signal processing and circuitry models that can link visual cortex anatomy, function, and dynamics

Micro-probing enables fine-grained mapping of neuronal populations using fMRI

The characterization of receptive field (RF) properties is fundamental to understanding the neural basis of sensory and cognitive behaviour. The combination of non-invasive imaging, such as fMRI, with biologically inspired neural modelling has enabled the estimation of population RFs directly in humans. However, current approaches require making numerous a priori assumptions, so these cannot reveal unpredicted properties, such as fragmented RFs or subpopulations. This is a critical limitation in studies on adaptation, pathology or reorganization. Here, we introduce micro-probing (MP), a technique for fine-grained and largely assumption free characterization of multiple pRFs within a voxel. It overcomes many limitations of current approaches by enabling detection of unexpected RF shapes, properties and subpopulations, by enhancing the spatial detail with which we analyze the data. MP is based on tiny, fixed-size, Gaussian models that efficiently sample the entire visual space and create fine-grained probe maps. Subsequently, we derived population receptive fields (pRFs) from these maps. We demonstrate the scope of our method through simulations and by mapping the visual fields of healthy participants and of a patient group with highly abnormal RFs due to a congenital pathway disorder. Without using specific stimuli or adapted models, MP mapped the bilateral pRFs characteristic of observers with albinism. In healthy observers, MP revealed that voxels may capture the activity of multiple subpopulations RFs that sample distinct regions of the visual field. Thus, MP provides a versatile framework to visualize, analyze and model, without restrictions, the diverse RFs of cortical subpopulations in health and disease.</p

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

Abnormal Brain Connectivity in the Primary Visual Pathway in Human Albinism

In albinism, the ipsilateral projection of retinal axons is significantly reduced, and most fibres project contralaterally. The retina and optic chiasm have been proposed as sites for misrouting. The number of lateral geniculate nucleus (LGN) relay neurons has been linked to LGN volume, suggesting a correlation between LGN size and the number of tracts traveling through the optic radiation (OR) to the primary visual cortex (V1). Using diffusion data and both deterministic and probabilistic tractography, we studied differences in OR between albinism and controls. Statistical analyses measured white matter integrity in areas corresponding to the OR, as well as LGN to V1 connectivity. Results revealed reduced white matter integrity and connectivity in the OR region in albinism compared to controls, suggesting altered structural development. Previous reports of smaller LGN and the altered thalamo-cortical connectivity reported here demonstrate the effect of misrouting on structural organization of the visual pathway in albinism

Connecting the Retina to the Brain

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Work in the laboratory of LE is funded by the BBSRC [BB/J00815X/1] and the R.S. Macdonald Charitable Trust. Research in the laboratory of EH is funded by grants from the Regional Government [Prometeo2012-005], the Spanish Ministry of Economy and Competitiveness [BFU2010-16563] and the European Research Council [ERC2011-StG20101109].Peer reviewedPublisher PD

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

Towards the right way of seeing what is left in Homonymous Hemianopia

Homonymous Hemianopia (HH) refers to one-sided blindness due to unilateral visual pathway damage. To determine the potential of individuals with HH to recover, it is important to consider the functional and structural integrity of their entire visual brain. In her thesis "Towards the right way of seeing what is left in Homonymous Hemianopia'', Hinke describes four exploratory neuroimaging studies and with that showed how the functional and structural integrity of the visual system changes in individuals with HH and how brain activity can inform us about the residual visual functioning of individuals with HH. In particular, she has shown that 1) the extent of collateral damage, i.e. damage in addition to the initial damage, is more widespread than previously reported and even affects the contralateral "healthy" hemisphere; 2) the visual system can functionally reorganize in response to surgical removal of one of the hemispheres (i.e. a hemispherectomy); 3) the functional connectivity strength between the precuneus and the occipital pole can predict training-induced visual recovery; and 4) visual field reconstructions based on brain activity can reveal parts of the "blind" visual field with preserved visual processing. With these findings, she has shed light on aspects that may be critical when determining the recovery potential of individuals with HH