Vision recovery in cortical blindness

皮质失明的视力恢复

• 批准号: 10634933
• 负责人: Krystel R Huxlin
• 金额: $ 2.31万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634933
• 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.

在成年期，中风对初级视觉皮层（V1）的损害会导致对侧意识的大量丧失， 视觉称为偏盲或皮质盲（CB）。虽然这种情况影响了多达50万新 仅在美国，每年就有200多例病例，完全缺乏公认的视力恢复疗法-在显著 与运动皮层损伤患者的早发性物理疗法形成对比。二十年的 在慢性CB患者中工作，这些患者的缺陷被认为是稳定的、永久的，因此适合科学研究 研究，已经产生了一种能够在长期V1损伤后恢复视力的方法：凝视- 视情况而定的视觉训练，以检测或辨别盲场中的刺激。在过去的两个补助金期间，我们 已经在该领域取得了明确的领导地位，为CB的有效治疗提供了希望， 地平线然而，在描述训练诱导的恢复及其潜在机制的同时，我们还 发现慢性CB的恢复需要数月的日常训练，恢复的视力是低对比度的， 粗糙，受到过多的内部处理噪音的影响，并局限于盲区周边。 越来越多的证据表明，这些限制可能会发生，因为慢性病人已经失去了一个 不仅在V1，而且通过逆行， 退变，在背外侧膝状体核（dLGN）和视网膜。我们新的试验数据显示亚急性CB 中风后<6个月的患者缺乏明显的变性迹象，超过一半的亚急性 测试保留视觉辨别能力，在他们的盲目领域，这消失了开始的慢性 期（卒中后6个月）。此外，当训练被管理到subacutes，他们恢复了 与慢性病患者相同的辨别能力，但更快，并且恢复更深地延伸到他们的盲人 领域这些数据构成了检验塑料存在实质性差异这一假设的有力前提 可以利用亚急性和慢性V1-卒中视觉系统之间的潜力， 在CB中恢复，并且可实现的恢复程度受到逆行量的限制。 退化持续。我们现在建议：（目标1）评估视觉表现如何与结构 V1卒中后亚急性期逆行性变性的证据。我们将在第二个目标中评估 亚急性训练对盲区功能、退行性变的进展和 在慢性期持续的训练诱导恢复潜力。最后，我们将（目标3）对比 在亚急性和慢性CB知觉学习的机制基板。总而言之，所提出的工作是独一无二的 在这一领域，它将通过产生全新的知识和理解， 人类永久性V1损伤后早期视觉可塑性电位随时间的变化。这 知识是重要的神经科学，并为设计更有效的治疗和现实的 对这一不断增长的患者群体的预期结果。