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

V1 损伤后 V2 拓扑的变化：微刺激对行为的影响

• 批准号: 7747987
• 负责人: Stelios Manolis Smirnakis
• 金额: $ 36.97万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7747987
• 关键词: Address; Adult; Affect; Animals; Area; Arts; Awareness; Behavior; Behavioral; Blood Circulation; Brain; Bypass; Chronic; Complement component C1s; Complex; Conscious; Contrast Sensitivity; Data; Detection; Disease; Drops; Drug Formulations; Electric Stimulation; Electrophysiology (science); Excision; Family; Feedback; Figs - dietary; Functional Magnetic Resonance Imaging; Future; Hemorrhage; Homonymous Hemianopia; Human; Individual; Infarction; Injury; Intervention; Knowledge; Lesion; Macaca; Measurement; Mediating; Methods; Modeling; Molecular; Monkeys; Morbidity - disease rate; Nature; Nervous system structure; Output; Pathway interactions; Patients; Pattern; Perception; Performance; Photic Stimulation; Plastics; Primates; Process; Property; Recovery; Reporting; Residual state; Scotoma; Sensitivity and Specificity; Series; Signal Transduction; Site; Societies; Stroke; Structure; System; Techniques; Testing; Time; Training; Traumatic Brain Injury; V2 neuron; Vision; Visual; Visual Cortex; Visual Fields; Visual Perception; Visual system structure; area V1; area V2; area striata; base; behavior influence; behavior measurement; blind; blood oxygen level dependent; design; driving behavior; electrical microstimulation; experience; extrastriate; extrastriate visual cortex; imaging modality; improved; interdisciplinary approach; microstimulation; nonhuman primate; public health relevance; receptive field; reconstitution; repaired; research study; response; retinotopic; therapy design; tool; visual information; visual performance

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.

描述（申请人提供）：脑部疾病与患者及其家庭的高发病率相关，并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，有必要详细研究成年人的大脑如何在损伤后进行调整，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区是视觉信息向纹外视区传递的主要中继区，因此原发性视皮层损伤产生密集的视野暗点并不奇怪。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，即灵长类动物（人和猴）受试者在完全区域V1损伤后在其视野的盲部分中仍然具有显著的残余视觉能力（参见Weiskrantz，Prog. 144：229-41，2004进行综述）。这种现象被称为“盲视”，反映了V1损伤后剩余的视觉感知能力很弱，需要特定的条件才能表现出来，并且通常与缺乏视觉意识有关。这些限制使患者基本上不可能利用这种能力获得实际利益。“失明”可能是由几条途径之一介导的，这些途径可以通过绕过V1区将信息传递到纹外皮层，但涉及的区域尚未最终破译。V2区，因为它的状态作为下一个皮层中继视觉信息后V1，是一个有吸引力的候选人调解“盲视”，以及一个有吸引力的目标，旨在恢复或加强视觉驱动的行为后V1病变的操作。人类功能性磁共振成像（fMRI）研究最近证明了在V1区损伤后数年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，其显示在慢性V1损伤后一个月，V2区的去传入部分内显著的视觉驱动激活（Schmid等人，神经科学学会ABS. 122.2，2007）。不幸的是，这种程度的V2区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fMRI和电生理学：i）研究在存在和不存在训练的情况下V1损伤后V2区重组的地形和机制，ii）将V2重组的强度与相关对比检测任务中的行为恢复相关联，以及iii）通过在训练期间将视觉刺激与皮质内微刺激配对，促进V2区重组，永久改善行为表现。迄今为止，还没有可靠的方法可以成功地使患有初级视皮层损伤的受试者康复，这些受试者在视野的受影响部分中经历了视觉感知的严重丧失。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以改善行为（“盲视”）表现。结合电生理学方法和功能磁共振成像研究的猕猴模型的皮层重组是一个通用的和敏感的工具，用于测试可塑性的性质的实验假设。公共卫生相关性：迄今为止，还没有可靠的方法来有效地康复患有初级视皮层损伤的受试者，这些受试者在视野的受影响部分中经历了视觉感知的严重丧失。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来研究初级视觉皮层损伤后V2区皮层重组的程度，以及它如何与相关视觉任务中改善的行为表现相关。此外，我们将重点研究V2区作为未来干预目标的潜力，并将专门测试一种有希望的干预（微刺激）提高性能的能力。