Vision recovery in cortical blindness

皮质失明的视力恢复

• 批准号: 10570616
• 负责人: Krystel R Huxlin
• 金额: $ 5.5万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570616
• 关键词: Adult; Affect; Animal Model; Attention; Blindness; Cell Death; Chronic; Complex; Conscious; Contralateral; Cortical Blindness; Cues; Data; Discrimination; Dorsal; Goals; Grant; Hemianopsia; Human; Image; Impairment; Intervention; Knowledge; Lateral Geniculate Body; Leadership; Link; Location; Magnetic Resonance Imaging; Measurable; Measures; Methods; Motion; Motor Cortex; Neurons; Noise; Optic tract structure; Optical Coherence Tomography; Outcome; Participant; Patients; Perception; Perceptual learning; Persons; Physical therapy; Property; Psychological Transfer; Psychophysics; Quality of life; Randomized; Recovery; Research; Residual state; Retina; Retinal Ganglion Cells; Retrograde Degeneration; Stimulus; Stroke; Testing; Time; Training; Vision; Visual; Visual Pathways; Visual system structure; Work; area striata; blind; brain magnetic resonance imaging; clinical practice; cost; early onset; effective therapy; expectation; gaze; human model; improved; insight; luminance; novel; patient population; post stroke; preservation; restoration; sight restoration; stroke rehabilitation; visual performance

In adulthood, stroke damage to the primary visual cortex (V1) causes a large, contralateral loss of conscious vision referred to as hemianopia or cortical blindness (CB). Although this condition affects up to ½ million new cases each year in the US alone, there is a total lack of accepted vision restoration therapies – in marked contrast with early-onset physical therapies prescribed to those with motor cortex damage. Two decades of work in chronic CB patients, whose deficits are deemed stable, permanent and thus amenable to scientific study, have generated one method consistently able to recover vision after long-standing V1 damage: gaze- contingent visual training to detect or discriminate stimuli in the blind field. Over the last 2 grant periods, we have taken clear leadership in the field, providing hope that an effective therapy for CB may finally be on the horizon. However, while characterizing training-induced recovery and its underlying mechanisms, we also found that recovery in chronic CB requires months of daily training and the vision restored is low-contrast, coarse, impaired by excessive internal processing noise and restricted to the blind field perimeter. Accumulating evidence suggests that these limitations may occur because chronic patients have lost a substantial portion of neurons that contribute to vision fundamentals not only in V1, but through retrograde degeneration, in the dorsal lateral geniculate nucleus (dLGN) and retina. Our new pilot data show subacute CB patients <6 months post-stroke to lack significant signs of degeneration, and more than half of subacutes tested retained visual discrimination abilities in their blind field, which disappeared by the start of the chronic period (6 months post-stroke). Moreover, when training was administered to subacutes, they recovered the same discrimination abilities as chronics, but much faster, and with recovery extending deeper into their blind field. These data form a strong premise for testing the hypothesis that substantial differences in plastic potential between subacute and chronic V1-stroke visual systems can be exploited to maximize visual restoration in CB, and that the extent of recovery attainable is limited by the amount of retrograde degeneration sustained. We now propose to: (Aim 1) assess how visual performance relates to structural evidence of retrograde degeneration in the subacute period post-V1-stroke. We will then (Aim 2) assess the impact of subacute training on blind-field functions, the progression of retrograde degeneration and the continued potential for training-induced recovery in the chronic period. Finally, we will (Aim 3) contrast mechanistic substrates of perceptual learning in subacute & chronic CB. All in all, the work proposed is unique in the field, which it stands to advance significantly by generating entirely new knowledge and understanding of the change in visual plastic potential with time in the early period after permanent V1 damage in humans. This knowledge is important both neuro-scientifically, and for devising more effective treatment and realistic outcome expectations for this growing patient population.

成年后，对主要视觉皮层（V1）的中风损害会导致大而对侧的意识丧失 视力称为半偏见或皮质失明（CB）。尽管这种情况会影响高达½百万的新 仅在美国，每年的病例都完全缺乏公认的视力恢复疗法 - 标记为 与患有运动皮层损伤的人开处的早期物理疗法形成对比。二十年的 在慢性CB患者中的工作，其防御性被认为是稳定，永久性且因此适合科学的。 研究，已经产生了一种始终能够在长期V1损害后恢复视力的方法： 偶然的视觉训练以检测或区分盲场的刺激。在过去的两个赠款期间，我们 已经在该领域取得了明确的领导，希望对CB进行有效的疗法，最终可能会出现 地平线。但是，在表征训练引起的恢复及其基本机制的同时，我们也 发现慢性CB的恢复需要每日训练数月，而恢复视力是低对比度的， 粗糙，受到过度内部处理噪声的损害，并且仅限于盲场周边。 积累的证据表明，可能会发生这些限制，因为慢性患者失去了 不仅在V1中，而且通过逆行，大部分神经元有助于视觉基础 堕落，在背侧侧向核核（DLGN）和视网膜中。我们的新飞行员数据显示了亚急性CB 中风后<6个月的患者缺乏重大变性迹象，超过一半的亚纯净迹象 经过测试的保留视觉歧视能力在其盲区中，该领域在慢性开始时消失了 时期（冲程后6个月）。此外，当对亚急性进行培训时，他们恢复了 与时期的歧视能力相同，但速度更快，并且恢复更深入地扩展到他们的盲人 场地。这些数据构成了测试塑料实质性差异的假设的有力前提 可以探索亚急性和慢性v1-stroks Visual系统之间的潜力，以最大化视觉 CB中的恢复，并且可以实现的恢复程度受到逆行量的限制 堕落得以维持。我们现在建议：（目标1）评估视觉性能与结构的关系 V1-STROKE后亚急性时期逆行变性的证据。然后，我们将（AIM 2）评估 亚急性训练对盲场功能的影响，逆行变性的进展和 持续的训练引起的慢性恢复潜力。最后，我们将（AIM 3）对比 亚急性和慢性CB中知觉学习的机械基板。总而言之，提议的工作是独一无二的 在该领域，它可以通过产生全新的知识和对 在人类永久性V1损害后，在早期的时间内随时间变化的视觉塑料潜力变化。这 知识既重要，既重要，既是神经方面的，并且对于设计更有效的治疗和现实是 对这个不断增长的患者人群的结果期望。