Understanding degeneration and the capacity for reorganisation in the adult human visual cortex
Keywords: Resting State
Optical Coherence Tomography
Cortical Degeneration
Visual Acuity
Stargardt Disease
Gamma-Aminobutyric Acid
Dual Regression
Vision Loss
Eye Tracking
Myo-inositol
1H-MRS
Primary Visual Cortex
Colour Vision
Cortical Thickness
Microperimetry
Neuroscience
N-acetylaspartate
Inherited Retinal Degeneration
Glutamate
Retinal Sensitivity
Cortical Reorganisation
Magnetic Resonance Spectroscopy Imaging
Magnetic Resonance Imaging
Functional Connectivity
Voxel-Based Morphometry
Contrast Sensitivity

Stargardt Macular Dystrophy (STGD1) causes degeneration of the photoreceptors, predominantly constrained to the cones within the central retina, which causes a loss of high acuity vision within the central visual field. Due to the topographic organisation of the primary visual cortex (V1), photoreceptor degeneration starting in the central retina projects to a focal region within posterior V1. There are treatments in development that aim to restore loss at the retina, however the majority of visual processing takes place in the visual cortex. Therefore, it is vital to determine if the visual cortex degenerates after a prolonged lack of input, as therapies that improve retinal function may not optimally restore vision if the visual cortex cannot respond to the new input. Previous research has shown that after a loss of visual input there are changes in the structure (Olivo et al., 2015, Burge et al., 2016; Hanson et al., 2019), function (Baseler et al., 2011) and neurochemistry (Bernabeu et al., 2009; Weaver et al., 2013) of the visual cortex.
The work presented in this thesis demonstrates the effects of vision loss on the adult visual cortex from a cohort with STGD1 compared to controls with healthy vision. I quantified the vision loss from STGD1 by measuring photoreceptor layer thickness, retinal sensitivity, and measures of visual function. I then used MRI measures of cortical structure, functional connectivity, and neurochemistry to investigate how vision loss affects the visual cortex.
Unsurprisingly, given the loss of cone photoreceptors in STGD1, these participants had reductions in retinal sensitivity, visual function, and photoreceptor layer thickness compared to controls. Firstly, using measures of cortical thickness, I found significant thinning of the grey matter within V1 in STGD1, suggesting that neuronal degeneration occurs after a loss of visual input. Furthermore, using resting state fMRI I found decreased functional connectivity between V1 and the LOC in STGD1. The LOC processes object recognition which requires high acuity vision. The visual loss in STGD1 is localised to the central visual field which is responsible for high acuity vision, and this is needed for object recognition. Connectivity from the region of projected loss (posterior V1) to the frontal cortex is also reduced in STGD1, suggesting a reduction in attentional modulation to the central part of the visual field. Finally, using MRSI, I found elevated myo-Ins levels, which are a marker for glial cell proliferation, within V1 in STGD1 compared to controls. This suggests that there is an increase in glial cells, which are responsible for repairing degenerating neurons within V1 from a loss of visual input in STGD1. Glutamate, which is a marker for neuronal function, was decreased within V1 in STGD1 compared to controls. This suggests a lack of functional activation within V1 due to a lack of input from vision loss in STGD1. GABA levels, which are a marker for neuronal inhibition, did not change in STGD1 compared to controls, however due to macromolecule contamination within the posterior visual cortex, this made accurate GABA quantification difficult.
This thesis demonstrates the effects of a loss of sensory input on the visual system by investigating degeneration and the capacity for reorganisation within the adult visual cortex. I found reduced functional connectivity, cortical thinning, elevated myo-Ins and reduced glutamate levels within V1, which are markers for cortical degeneration. In contrast markers for reorganisation (increased functional connectivity, increased glutamate, and decreased GABA) were not found. Therefore, I conclude that after a loss of visual input in adulthood, the visual cortex degenerates and has less of a capacity for reorganisation. These findings should be considered for treatments that aim to restore input at the retina, to optimally restore visual function, the treatment should be conducted as soon as possible after photoreceptor loss before cortical degeneration occurs.