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

描述（由申请人提供）：脑部疾病是患者及其家属的高发病率疾病，给个人和社会带来巨大负担。了解大脑的可塑性是设计旨在增强神经系统损伤后恢复能力的治疗方法的重要一步。因此，有必要详细研究成人大脑在损伤后如何调整以及促进适应性重组的条件。视觉功能障碍是皮层损伤的常见后果。V1区是视觉信息向外视区传递的主要区域，因此原发性视觉皮质损伤产生致密的视野暗斑并不奇怪。然而，在过去25年中进行的一系列研究提供了强有力的证据，表明灵长类动物（人类和猴子）受试者在完全V1区病变后，在其视野的失明部分仍然具有显著的残余视觉能力(见Weiskrantz， Prog。中国医学杂志，2004,44(1):229-41。这种现象被称为“盲视”，反映了V1病变后剩余的视觉感知能力较弱，需要特定条件才能表现出来，并且通常与缺乏视觉意识有关。这些限制使得患者基本上不可能利用这种能力获得实际利益。“盲视”可能是由几种途径中的一种介导的，这些途径可以绕过V1区向外皮层传递信息，但涉及的区域尚未被最终破译。V2区作为继V1之后的下一个视觉信息的皮层中继，是介导“盲视”的一个有吸引力的候选区域，也是旨在恢复或加强V1病变后视觉驱动行为的操作的一个有吸引力的目标。人类功能磁共振成像（fMRI）最近的研究表明，V1区病变后几年V2活动(Baseler等，神经科学杂志19(7):2619-27,1999；Schoenfeld等人。神经神经学报，32(6):814- 824,2002)。这与我们自己在猕猴孤立V1损伤模型中的初步fMRI数据一致，该数据显示，在慢性V1损伤一个月后，V2区失传入部分内明显的视觉驱动激活（Schmid等人，Soc）。>。Abs. 122.2, 2007)。不幸的是，这种程度的V2区再激活显然不足以恢复高水平的视觉表现。本研究拟利用猕猴功能磁共振成像（fMRI）和电生理技术，研究训练前后V1损伤后V2区域重组的地形和机制；在相关对比检测任务中，将V2重组的强度与行为恢复联系起来；在训练过程中，通过视觉刺激和皮质内微刺激相结合，促进V2区域重组，从而永久改善行为表现。到目前为止，还没有可靠的方法能够成功地恢复受初级视觉皮层损伤的受试者，他们在视野的受影响部分经历了严重的视觉感知丧失。我们的实验将探索V2区域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（“盲视”）表现的作用。电生理与功能磁共振相结合的猕猴皮层重组模型是检验可塑性本质实验假设的一种通用而灵敏的工具。公共卫生相关性：迄今为止，没有可靠的方法可以有效地恢复受初级视觉皮层损伤的受试者，他们在视野的受影响部分经历了严重的视觉感知丧失。本实验结合最新的功能磁共振成像和电生理学方法，研究了原发性视觉皮质损伤后V2区皮层重组的程度及其与相关视觉任务中行为表现改善的关系。此外，我们将重点研究V2区域作为未来干预目标的潜力，并将专门测试一种有前景的干预（微增产）的能力，以提高产量。

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.