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

困扰大脑的疾病与患者及其家人的高发病率有关，并导致巨大的 给个人和社会带来负担。了解大脑的可塑性能力是努力 设计旨在增强神经系统在受伤后恢复能力的治疗方法。因此，至关重要的是 详细研究成年大脑在受伤后如何调整，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推论。V1区提供了主要的视觉信息，以根除 因此，原发视觉皮质损伤会导致密集的视野暗点也就不足为奇了。不过， 过去25年进行的一系列研究提供了强有力的证据，证明灵长类(人和猴子) 在完成V1区后，受试者在其视野盲部仍具有显著的残余视力 损伤(见Weiskrantz，Prog.Brain Res.144：229-41,2004年，供回顾)。这种现象被称为“失明”。 反映V1损伤后残留的视觉知觉能力较弱的事实，需要特定的条件 表现出来的，通常与缺乏视觉意识有关。这些限制使它基本上 患者不可能将这种能力用于实际利益。《盲目》很可能是由几个人中的一个 可以通过绕过V1区向外纹状体皮质传递信息的通路，但涉及的区域尚未被 最终破译了。由于V2区是继V1之后的下一个视觉信息皮质中继区，因此它是一个 有吸引力的候选人，以调解“失明”，以及有吸引力的目标，以操纵旨在恢复或 加强V1损伤后的视觉驱动行为。人体功能磁共振成像(FMRI)研究 最近在V1区病变后的几年内表现出V2活动(Baseler等人，J Neurosci 19(7)：2619-27,1999； Schoenfeld等人的研究成果。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。 单独的V1损伤，在V2区的传出部分逐一显示显著的视觉驱动激活 慢性V1病变后一个月(Schmidet al.，Soc.神经科。腹肌。122.2、2007年)。不幸的是，这种程度的面积 V2的重新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 猕猴功能磁共振成像和电生理学：I)研究V1后V2区的地形图和重组机制 有无训练造成的损害，II)V2重组的强度与行为恢复有关 相关的对比度检测任务，以及iii)通过将视觉刺激与 训练期间皮质内微刺激以促进V2区重组。到目前为止，还没有可靠的方法来 成功修复视力严重丧失的初级视觉皮质损伤患者 视野中受影响部分的知觉。我们的实验将探索V2区作为目标的潜力 未来的干预，并将专门测试皮质内微刺激改善行为(“失明”) 性能。电生理学方法结合研究猕猴皮质重组模型 而功能磁共振成像是一种多功能和灵敏的工具，用于测试关于可塑性本质的实验假说。

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.