Enhancing cortical networks with spike-triggered intracortical microstimulation

通过尖峰触发的皮质内微刺激增强皮质网络

• 批准号: 9018376
• 负责人: MARC H SCHIEBER
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9018376
• 关键词: Address; Affect; Animals; Behavior; Behavioral; Cerebral Palsy; Cerebral cortex; Chronic; Development; Electrodes; Hand; Hour; Human; Individual; Learning; Maps; Microelectrodes; Nature; Nervous System Trauma; Neuronal Plasticity; Neurons; Output; Patients; Performance; Peripheral Nerve Stimulation; Physiologic pulse; Plastics; Population; Recovery; Resources; Sclerosis; Site; Spinal cord injury; Stroke; Sum; System; Task Performances; Techniques; Technology; Testing; Time; Traumatic Brain Injury; Work; awake; brain computer interface; electrical microstimulation; high risk; human subject; improved; in vivo; microstimulation; mind control; nervous system disorder; neural circuit; public health relevance; relating to nervous system; technique development; technology development; tool

 DESCRIPTION (provided by applicant): Spike-timing dependent plasticity (STDP) is a mechanism thought to underlie much of normal learning, as well as recovery from nervous system injury. The ability to manipulate STDP in selected neural circuits, and specifically during certain behaviors, therefore could have vast potential for enhancing normal learning as well as treating a wide variety of neurological disorders. Indeed, previous work has shown that changes consistent with STDP can be produced in normal humans and in patients with spinal cord injury. These studies have paired i) transcranial stimulation of the corticospinal system with ii) peripheral nerve stimulation, both of which stimulate thousands of neurons at each site, inducing plastic changes relatively nonspecifically in large populations of neurons. Recently, the development of technology for brain-computer interfaces has enabled studies in which spikes recorded from a single neuron in an awake subject can be used to trigger intracortical microstimulation (ICMS) at another electrode with delays appropriate for producing STDP. Three studies have suggested that such spike-triggered ICMS (SpTr-ICMS) can alter cortical output, increase connections between neurons, and modify behavior. But in each of these studies SpTr-ICMS has been delivered continuously over days, during which the subject engaged in a wide variety of unrestrained, natural behaviors. The present proposal therefore aims to address the following questions: 1) Can SpTr-ICMS alter neuronal activity and interactions during a specific behavior when the stimulation is delivered during only that one behavior? 2) Does SpTr-ICMS delivered during one behavior alter neuronal activity and interactions during another behavior? And 3) Does SpTr-ICMS delivered during one behavior produce improvement in that behavior without detrimental effects on another behavior? The high risk of the present R21 proposal lies in the possibility that SpTr-ICMS delivered for only a few hours each day during a specific behavior may be insufficient to induce any changes, or that the changes induced may be non-specific. The potentially high payoff lies in the possibility that SpTr-ICMS will provide a new tool for experimental manipulations that probe the nature and limits of neural plasticity. Such progress would open the way for translational development of SpTr-ICMS as new means of enhancing selected aspects of learning, as well as promoting recovery of specific functions after nervous system injury.

 描述（由申请人提供）：尖峰定时依赖可塑性（STDP）是一种被认为是许多正常学习以及神经系统损伤恢复的基础的机制。 在选定的神经回路中操纵STDP的能力，特别是在 因此，某些行为可能具有增强正常学习以及治疗各种神经系统疾病的巨大潜力。 事实上，以前的工作已经表明，与STDP一致的变化可以在正常人和脊髓损伤患者中产生。 这些研究将i）皮质脊髓系统的经颅刺激与ii）外周神经刺激配对，两者都会刺激每个部位的数千个神经元，从而在大量神经元中相对非特异性地诱导可塑性变化。 近日 脑-机接口技术的发展使得能够进行这样的研究，其中从清醒受试者中的单个神经元记录的尖峰可以用于在另一电极处触发具有适于产生STDP的延迟的皮质内微刺激（ICMS）。 三项研究表明，这种尖峰触发的ICMS（SpTr-ICMS）可以改变皮层输出，增加神经元之间的连接，并改变行为。 但在这些研究中，SpTr-ICMS已经连续几天被提供，在此期间，受试者参与了各种各样的不受约束的自然行为。 因此，本提案旨在解决以下问题：1）当刺激仅在特定行为期间递送时，SpTr-ICMS能否改变该特定行为期间的神经元活动和相互作用？ 2)在一种行为中传递的SpTr-ICMS是否会改变另一种行为中的神经元活动和相互作用？ 和3）在一个行为过程中提供的SpTr-ICMS是否会改善该行为而不会对另一个行为产生不利影响？ 目前R21建议的高风险在于，在特定行为期间每天仅提供几个小时的SpTr-ICMS可能不足以引起任何变化，或者引起的变化可能是非特异性的。 潜在的高回报在于SpTr-ICMS将为探索神经可塑性的性质和限制的实验操作提供一种新的工具。 这种进展将为SpTr-ICMS的翻译开发开辟道路，作为增强学习的选定方面以及促进神经系统损伤后特定功能恢复的新手段。