Understanding Degeneration and the Capacity for Reorganisation in the Adult Human Visual Cortex

婴儿期的视力丧失导致视觉皮质1-3的功能重组；这表明大脑如何在生命早期适应改变的感觉输入。很多人都知道成年人的大脑如何对异常的视觉输入做出反应，如何适应试图恢复视觉功能的治疗。由于遗传性视网膜疾病是发达国家导致失明的主要原因，未来十年对治疗的需求将会增加。即使在有治疗方法的地方，大脑也需要能够解释恢复的感觉输入，目前还不清楚在长期失去输入后这是否可能。为了最佳地恢复功能，了解成人大脑如何对感觉输入的丢失做出反应的原理是至关重要的。Stargardt病(STGD)是一种视网膜疾病，其中心视力受到的影响最大。本项目将测量STGD患者视觉系统的纵向变化，并将在Holly Bridgee教授的监督下完成。目的1)STGD中视网膜变性的皮质效应以前的研究已经调查了视网膜疾病中结构和功能的变化4，5。25名STGD患者和25名年龄匹配的对照组将被招募进行与STGD相关的皮质变化的横断面调查。这将使用磁共振波谱成像(MRSI)、结构磁共振成像、扩散加权成像和群体感受野(PRF)映射来测量。然后将视网膜功能的临床测量与这些测量进行比较。2)对STGD视网膜变性的纵向研究由于STGD的视网膜退化可能很快，许多患者在两年后表现出无损伤功能的下降。为了量化这种输入和功能丧失对视皮层的影响，患者将在两年后重新扫描。通过测量相同核磁共振量的差异，我将能够直接证明视网膜退化对大脑的影响。3)评估增强健康视觉系统可塑性的潜力增加大脑的兴奋性被认为增加了可能发生的重组的数量；对成年动物的研究表明，当操纵神经化学环境时，这种变化可以发生。为了在视觉恢复后最大化视觉功能，可能有必要提高大脑皮层对恢复的输入做出反应的能力。在运动系统中，tdcs已被用作增加训练或康复的行为效果的辅助程序7，它对视觉系统的影响是众所周知的。20名志愿者将使用磁共振成像和功能磁共振成像(7T)进行扫描，以调查tDCS应用后发生的变化，首先是枕极，然后是HMT+。综上所述，该项目将确定由于视网膜退化而导致的视力丧失的直接后果，特别是在个别患者超时发生的变化。此外，该项目将评估使用tdcs提高视觉系统可塑性的潜力，这可能对优化视觉功能很重要。

Loss of vision in infancy results in functional reorganisation of the visual cortex1-3;this shows how the brain can adapt to an altered sensory input early in life. Much lessis known about how the adult brain reorganises in response to abnormal visual inputor how it might adapt to treatments that try to restore visual function. Since inheritedretinal diseases are the leading cause of blindness in the developed world, the demandfor therapy will increase in the next decade. Even where therapy is available, the brainneeds to be able to interpret the restored sensory input, and it is not clear whether thiswill be possible following prolonged loss of input. In order to optimally restorefunction it is vital to understand the principles of how the adult brain responds to aloss of sensory input.Stargardt disease (STGD) is a type of retinal disease in which central vision is mostaffected. This project will measure the longitudinal changes in the visual system ofpatients with STGD and will be completed under the supervision of Professor HollyBridge.Aims1) Cortical effects of retinal degeneration in STGDPrevious research has investigated structural and functional cortical changes in retinaldiseases4, 5. 25 STGD patients and 25 age-matched controls will be recruited toundertake a cross-sectional investigation of the cortical changes associated withSTGD. This will be measured using Magnetic resonance spectroscopy imaging(MRSI), structural MRI, diffusion-weighted imaging and population receptive field(pRF) mapping. Clinical measures of retinal function will then be compared to thesemeasures.2) Longitudinal investigation of reorganisation due to degeneration in STGDSince retinal degeneration can be rapid in STGD, many patients show a decrease invisual function after two years. To quantify the effects of this loss of input andfunction on the visual cortex, patients will be rescanned after two years. By measuringdifferences in the same MRI quantities, I will be able to directly demonstrate theeffects of retinal degeneration on the brain.3) Assessing the potential for boosting plasticity in the healthy visual systemIncreasing excitability in the brain is thought to boost the amount of reorganisationthat can take place; studies in adult animals have shown that this change can occurwhen manipulating the neurochemical environment6. In order to maximise visualfunction following visual restoration it may be necessary to boost the ability of thecortex to respond to restored input. In the motor system tDCS has been used as anadjunct procedure to increase behavioural effects of training or rehabilitation7, muchless is known of its effects in the visual system. 20 volunteers will be scanned usingMRSI and fMRI (7T) to investigate changes that occur following tDCS applicationfirstly to the occipital pole, and secondly to hMT+.To summarise, this project will determine the direct consequences of visual loss dueto retinal degeneration, specifically the changes that occur in individual patients overtime. Additionally, this project will assess the potential to boost plasticity in the visualsystem using tDCS, which may be important for optimising visual function.