Vision recovery in cortical blindness

在成年期，中风对初级视觉皮质(V1)的损害会导致对侧大量的意识丧失 视力称为偏盲或皮质盲(CB)。尽管这种情况影响了多达50万新的 仅在美国每年就有病例，完全缺乏公认的视力恢复疗法-在标记 与运动皮质损伤患者的早期物理疗法形成对比。二十年来 在慢性慢阻肺患者中工作，其缺陷被认为是稳定的、永久性的，因此符合科学 研究发现，在长期的V1损伤后，有一种方法能够持续恢复视力：凝视- 有条件的视觉训练，以检测或辨别盲区中的刺激。在过去的两个授权期内，我们 在这一领域取得了明显的领先地位，为治疗慢性支气管炎提供了希望，可能最终会出现有效的治疗方法 地平线。然而，在描述训练诱导的恢复及其潜在机制的同时，我们也 发现慢性慢性病的恢复需要几个月的日常训练，恢复的视力是低对比度的， 粗糙，受到过高的内部加工噪音的影响，仅限于盲场周边。 越来越多的证据表明，这些限制的发生可能是因为慢性患者失去了 不仅在V1，而且通过逆行对视觉基础有贡献的神经元的很大一部分 变性，在背外侧膝状核(DLGN)和视网膜。我们新的飞行员数据显示亚急性慢阻肺 中风后6个月的患者没有明显的退行性改变的迹象，超过一半的亚急性 受试者在他们的盲区保留了视觉辨别能力，这种能力在慢性病开始时就消失了 期间(卒中后6个月)。此外，当对潜水员进行训练时，他们恢复了 辨别能力与慢性病相同，但速度要快得多，而且康复更深入地影响到他们的盲人 菲尔德。这些数据为检验塑料中显著差异的假设提供了强有力的前提 可以利用亚急性和慢性V1卒中视觉系统之间的潜力来最大限度地提高视力 CB中的修复，而且可实现的恢复程度受到逆行的量的限制 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卒中后亚急性期退行性变的证据。然后我们将(目标2)评估 亚急性训练对盲区功能、退行性变进程和视神经功能的影响 在慢性期，训练导致的恢复仍有潜力。最后，我们将(目标3)进行对比 亚急性和慢性CB知觉学习的机制基础。总而言之，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来显著进步 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 知识在神经科学和设计更有效的治疗方法和现实中都是重要的。 对不断增长的患者群体的结果预期。

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.