Variability of Brain Reorganization in Blindness

项目摘要 严重的视力丧失影响着全球约4000万人1，随着人口老龄化，影响的人数会越来越多3。视力的成功 盲人感官辅助设备的恢复和使用取决于人们不太了解的因素：有些人不 尽管有侵入性手术，仍能获得功能性视力37 -40。要缓解这一问题，就需要了解减少的 大脑的视觉，这可能会妨碍康复工作。早发性失明后，视觉皮层（VC） 经历可塑性重组4 - 6，14，17，这可能会严重影响其处理恢复视力的能力， 补偿策略24.然而，很少有人努力去理解大脑重组的可变性 在盲人中的应用及其对视力恢复和补偿能力的影响。有助于改善 个性化的视觉康复，我们建议研究盲人大脑的多尺度变异性 使用神经成像和行为数据的时间、神经化学和空间分析。 首先，我们将研究盲人VC是否保留了高于典型的可塑性潜力与神经化学和时间 动态fMRI测量。由于视觉经验在早期发展促进VC稳定42，79，和短期 黑暗暴露会激发可塑性41，80，81，我们预测盲人个体的持续可塑性。这将澄清机制 以及利用和恢复成人可塑性以进行康复的潜力。 其次，我们将研究视觉体验如何影响大脑发育的个体差异， 失明导致大脑组织更加多变。盲人VC及其非典型脑区的脑内连接 非视觉任务的反应，我们将测试VC可塑性是否提供更多的变量结果，可以解释 关于VC在失明中的作用的相互矛盾的组水平结果。我们将研究VC补偿性的模式， 参与失明，测试失明的可塑性是否可以改变典型的VC感觉功能， 水平的认知作用，或者它是否受到神经解剖学限制的限制，阐明了人类可塑性的能力。 个脑袋 最后，我们将确定VC是否在所有盲人个体中具有单一一致的作用，或者是否具有不同的个体模式 出现了可以用于个性化康复的模式。我们将研究是否独特， 视觉稳定的全脑可塑性模式与盲人的补偿行为能力有关， 触觉82 -84，听觉63，85-87，记忆88 -92和语言93，94，并以VC非视觉招聘。我们将进一步利用这种 个体可塑性模式来预测哪些盲人可以从感官辅助（感官替代）中受益， 揭示了可塑性的不同亚型是否可以指示个体的行为能力，并被用作 康复生物标志物。 总的来说，这个项目将提高我们对失明时大脑可塑性原理的理解，并开辟一条道路， 定义用于视觉损伤的个性化治疗的生物标志物。

PROJECT SUMMARY Severe vision loss affects ~40 million people worldwide1 and more as the population ages3. The success of sight restoration and use of sensory aids for blind individuals depends on poorly-understood factors: some people do not gain functional sight despite invasive procedures37-40. Mitigating this problem requires mapping the impacts of reduced vision on the brain, which may preclude rehabilitation efforts. Following early-onset blindness, the visual cortex (VC) undergoes plastic reorganization4-6,14,17 that may crucially affect its capacity to process restored vision and employ compensatory strategies24. However, little effort has been made to understand the variability of brain reorganization across blind individuals and its implications for sight restoration and compensatory abilities. Contributing to improved individually-tailored visual rehabilitation, we propose to study multi-scale variability in the brains of blind individuals using temporal, neurochemical, and spatial analyses of neuroimaging and behavioral data. First, we will study if the blind VC retains a higher-than-typical plasticity potential with neurochemical and temporal dynamics fMRI measures. Since visual experience in early development facilitates VC stabilization42,79, and short-term dark exposure elicits plasticity41,80,81, we predict sustained plasticity in blind individuals. This would clarify mechanisms of brain maturation and the potential to harness and revive adult plasticity for rehabilitation. Second, we will investigate how visual experience affects individual differences in brain development, testing if blindness results in more variable brain organization. Assessing brain-wide connections of the blind VC and its atypical responses to non-visual tasks, we will test if VC plasticity affords more variable outcomes which can explain contradictory group-level findings about VC role in blindness. We will examine the pattern of VC compensatory engagement in blindness, testing whether plasticity in blindness can change typical VC sensory functions for higher- level cognitive roles or if it is restricted by neuroanatomical limitations, clarifying the capacity for plasticity in the human brain. Finally, we will determine if VC has a single consistent role in all blind individuals or if distinct individual patterns emerge, patterns that could be employed for individualized rehabilitation. We will examine whether unique and longitudinally-stable whole-brain patterns of plasticity relate to compensatory behavioral abilities in blind individuals for touch82-84, hearing63,85-87, memory88-92 and language93,94 and to VC non-visual recruitment. We will further use such individual plasticity patterns to predict which blind individuals may benefit from a sensory aid (sensory substitution), revealing if different subtypes of plasticity can indicate behavioral capacities across individuals and be employed as rehabilitation biomarkers. Overall, this project will improve our understanding of brain plasticity principles in blindness, and open a path to defining biomarkers for personalized treatments for visual impairment.