Enhancing cortical networks with spike-triggered intracortical microstimulation

 描述(由申请人提供)：峰时依赖可塑性(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，某些行为在加强正常学习和治疗各种神经疾病方面具有巨大的潜力。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1)经颅刺激皮质脊髓系统与2)周围神经刺激结合在一起，这两种刺激都在每个部位刺激数千个神经元，在大量神经元中诱导相对非特异性的可塑性变化。最近， 脑机接口技术的发展使研究成为可能，在这些研究中，从清醒受试者的单个神经元记录的棘波可以用来在另一个电极上触发皮质内微刺激(ICMS)，其延迟适合于产生STDP。三项研究表明，这种尖峰触发的ICMS(SPTR-ICMS)可以改变皮质输出，增加神经元之间的连接，并改变行为。但在每一项研究中，SPTR-ICMS都是连续几天进行的，在此期间，受试者从事各种不受限制的、自然的行为。因此，目前的建议旨在解决以下问题：1)当刺激仅在一个行为中提供时，SPTR-ICMS能否改变特定行为中的神经元活动和相互作用？2)在一个行为中提供的SPTR-ICMS是否会改变另一个行为中的神经元活动和相互作用？3)在一种行为期间提供的SPTR-ICMS是否在不损害另一种行为的情况下改善了该行为？目前R21提案的高风险在于，在特定行为期间，每天只提供几个小时的SPTRICMS可能不足以引起任何变化，或者引起的变化可能是非特定的。潜在的高回报在于SPTR-ICMS将为探索神经可塑性的本质和极限的实验操作提供一种新的工具。这种进展将为SPTRICMS的翻译开发开辟道路，将其作为加强特定学习方面以及促进神经系统损伤后特定功能恢复的新手段。

 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.