Changes in V2 topography after V1 lesions: Impact of microstimulation on behavior

折磨大脑的疾病与患者及其家属的高发病率相关，并引起巨大的死亡率。 给个人和社会带来负担。了解大脑的可塑性是研究大脑可塑性的重要一步， 设计旨在增强神经系统损伤后恢复能力的治疗方法。因此，必须 详细研究成年人的大脑如何在受伤后进行调整，以及促进适应性重组的条件。视觉 功能障碍是皮质损伤的常见结果。V1区提供了主要的视觉信息中继， 因此，原发性视觉皮层损伤产生密集的视野暗点并不奇怪。然而，尽管如此， 过去25年来进行的一系列研究提供了强有力的证据，证明灵长类动物（人类和猴子） 受试者在完成V1区后，在其视野的盲部仍具有显著的残余视力 病变（参见Weiskrantz，Prog. 144：229-41，2004进行综述）。这种现象被称为“盲视” 反映V1损伤后剩余的视觉感知能力弱的事实，需要特定的条件 通常与缺乏视觉意识有关。这些限制使其基本上 患者不可能将这种能力用于实际利益。“失明”很可能是由几种 这些通路可以通过绕过V1区将信息传递到外纹状皮层，但涉及的区域还没有被激活。 最终被破译。由于V2区是继V1区之后视觉信息的下一个皮层中继区，因此V2区是视觉信息的下一个皮层中继区。 有吸引力的候选人调解“盲视”，以及一个有吸引力的目标，旨在恢复或操纵 加强V1病变后的视觉驱动行为。人体功能性磁共振成像（fMRI）研究 最近证实了V1区损伤后数年的V2活动（Baseler等人，神经科学杂志19（7）：2619- 27，1999; Schoenfeld等人，Ann Neurol 52（6）：814-24，2002）。这与我们自己在猕猴模型中的初步fMRI数据一致 孤立V1损伤，其中显示出显著的视觉驱动激活内的V2区的去传入部分，由一个 慢性V1损伤后1个月（Schmid等，神经科学学会ABS. 122.2，2007）。不幸的是，这种面积 V2再激活显然不足以重建高水平的视觉表现。在这里，我们建议使用 猕猴的功能磁共振成像和电生理学：i）研究V1后V2区重组的地形和机制 损伤的存在和不存在的训练，ii）相关的V2重组的强度，以行为恢复， 相关对比度检测任务，以及iii）通过将视觉刺激与 训练期间进行皮质内微刺激以促进V2区重组。到目前为止，还没有可靠的方法， 成功地恢复了患有初级视觉皮层损伤的受试者，这些受试者经历了严重的视觉丧失， 在视野的受影响部分的感知。我们的实验将探索V2区作为靶点的潜力， 未来的干预，并将专门测试皮质内微刺激改善行为（“盲视”） 性能猕猴皮层重组模型的电生理学研究 功能磁共振成像是一种多功能和敏感的工具，用于测试可塑性本质的实验假设。

Diseases that afflict the brain are associated with high morbidity for patients and their families and incur a tremendous burden to individuals and to society. Understanding the brain's capacity for plasticity is an important step in the effort to design treatments aimed at enhancing the ability of the nervous system to recover after injury. Hence it is essential to study in detail how the adult brain adjusts after injury and the conditions that promote adaptive reorganization. Visual malfunction is a common corollary of cortical injury. Area V1 provides the chief relay of visual information to exstrastiate visual areas, so it is not surprising that primary visual cortical injuries produce a dense visual field scotoma. Nevertheless, a series of studies performed over the last 25 years has provided strong evidence that primate (human and monkey) subjects still possess significant residual visual capacity in the blind part of their visual field following complete area V1 lesions (see Weiskrantz, Prog. Brain Res. 144:229-41, 2004 for a review). This phenomenon has been dubbed "blindsight" reflecting the fact that the visual perceptual capacity remaining following V1 lesions is weak, requires specific conditions to be manifested, and is often associated with absence of visual awareness. These constraints make it essentially impossible for patients to use this capacity for practical benefit. "Blindsight" is likely mediated by one of several pathways that can convey information to exstrastriate cortex by bypassing area V1, but areas involved have not been conclusively deciphered. Area V2, because of its status as the next cortical relay of visual information following V1, is an attractive candidate for mediating "blindsight", as well as an attractive target for manipulations designed to restore or strengthen visually driven behavior following V1 lesions. Human functional magnetic resonance imaging (fMRI) studies recently demonstrated V2 activity several years following area V1 lesions (Baseler et al., J Neurosci 19(7):2619-27,1999; Schoenfeld et al. Ann Neurol 52(6):814-24, 2002). This agrees with our own preliminary fMRI data in a macaque model of isolated V1 injury, which show significant visually driven activation inside the deafferented portion of area V2 by one month following a chronic V1 lesion (Schmid et al., Soc. Neurosci. Abs. 122.2, 2007). Unfortunately, this degree of area V2 reactivation is evidently not sufficient to reconstitute high levels of visual performance. Here we propose to use macaque fMRI and electrophysiology to: i) study the topography and the mechanism of area V2 reorganization after V1 lesions in the presence and absence of training, ii) correlate the strength of V2 reorganization to behavioral recovery in a relevant contrast detection task, and iii) permanently improve behavioral performance by pairing visual stimulation with intracortical microstimulation during training to promote area V2 reorganization. To date no reliable method exists for successfully rehabilitating subjects with lesions of the primary visual cortex who experience a profound loss of visual perception in the affected portion of the visual field. Our experiments will explore the potential of area V2 as a target for future intervention, and will specifically test intracortical microstimulation for improving behavioral ("blindsight") performance. The macaque model of cortical reorganization studied with the combination of electrophysiology methods and fMRI is a versatile and sensitive tool for testing experimental hypotheses on the nature of plasticity.