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

描述(申请人提供)：困扰大脑的疾病与患者及其家人的高发病率有关，并给个人和社会造成巨大负担。了解大脑的可塑性是设计治疗方法的重要一步，目的是增强神经系统在受伤后恢复的能力。因此，有必要详细研究成年大脑在损伤后如何调整，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区为纹外视区提供主要的视觉信息传递，因此原发视皮层损伤导致密集的视野暗点也就不足为奇了。然而，过去25年进行的一系列研究提供了强有力的证据，表明灵长类(人和猴子)受试者在V1区完全损伤后，在其视野的盲区仍具有显著的残余视觉能力(见Weiskrantz，Prog。Brain Res.144：229-41,2004年，供回顾)。这种现象被称为“盲视”，反映了V1病变后残留的视觉感知能力较弱，需要特定的条件才能表现出来，而且通常与视觉意识的缺乏有关。这些限制使得患者基本上不可能将这种能力用于实际利益。“失明”可能是通过绕过V1区向纹外皮质传递信息的几条通路中的一条，但涉及的区域尚未被最终破译。由于V2区是继V1之后的下一个视觉信息的皮质中继区，因此它是调节“失明”的有吸引力的候选区域，也是设计用于恢复或加强V1损伤后的视觉驱动行为的手法的有吸引力的靶点。人类功能磁共振成像(FMRI)研究最近显示V1区病变后数年的V2活动(Baseler等人，J Neurosci 19(7)：2619-27,1999；Schoenfeld等人。Ann Neurol 52(6)：814-24,2002)。这与我们自己在孤立V1损伤的猕猴模型中的初步fMRI数据一致，该数据显示在慢性V1损伤后一个月，V2区的去传入部分有显著的视觉驱动激活(Schmid等人，Soc。神经科。腹肌。122.2、2007年)。不幸的是，这种V2区重新激活的程度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来：i)在有无训练的情况下研究V1损伤后V2区重组的地形图和机制，ii)在相关的对比检测任务中将V2区重组的强度与行为恢复相关联，以及iii)在训练期间通过将视觉刺激与皮质内微刺激相结合来促进V2区重组，从而永久性地改善行为表现。到目前为止，还没有可靠的方法来成功地恢复患有初级视觉皮质损伤的受试者，这些受试者在受影响的视野部分经历了严重的视觉丧失。我们的实验将探索V2区作为未来干预目标的潜力，并将专门测试皮质内微刺激对改善行为(失明)表现的作用。用电生理学方法和功能磁共振相结合的方法研究猕猴皮质重组模型，是检验关于可塑性本质的实验假说的一个通用和敏感的工具。与公共卫生相关：到目前为止，还没有可靠的方法来有效地恢复初级视觉皮质损伤的受试者，这些受试者在受影响的视野部分经历了严重的视觉丧失。我们的实验结合了最先进的功能磁共振成像和电生理学方法，以研究初级视觉皮质损伤后V2区皮质重组的程度，以及它如何与相关视觉任务中行为表现的改善有关。此外，我们将重点研究V2区作为未来干预目标的潜力，并将具体测试其中一种有希望的干预(微刺激)提高成绩的能力。

DESCRIPTION (provided by applicant): 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 extrastriate 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 extrastriate 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. PUBLIC HEALTH RELEVANCE: To date no reliable method exists to rehabilitate effectively 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 couple state of the art functional magnetic resonance imaging and electrophysiology methods to study the degree of cortical reorganization in area V2 following primary visual cortical injury and how it relates to improved behavioral performance in a relevant visual task. In addition, we will focus on investigating the potential of area V2 as a target for future intervention, and will specifically test the capacity of one such promising intervention (microstimulation) for improving performance.