NCS-FO: Probing the Functional Significance of Brain Oscillations through Closed-Loop Phase-Locked Stimulation

人们很早就知道大脑中的振荡活动，但它的功能意义仍在争论中。最近有人提出，神经振荡在控制信息在大脑中的流动方式以及哪些神经元能够交换信息方面发挥了重要作用，使大脑能够灵活地调整以适应不同的任务需求。虽然这一观点得到了来自特定子系统的大脑活动记录的支持，但对这些想法的严格测试需要操纵大脑活动，以建立同步大脑活动和神经交流之间的因果联系。虽然抑制或增强神经活动的实验技术是现成的，但解决这个科学问题需要新的技术来操纵神经活动，与正在进行的神经活动具有精确的时间关系。该研究项目的目标是开发一种闭环刺激系统，该系统可以实时分析正在进行的大脑振荡，并使用产生的信息来触发神经刺激。这允许操纵神经活动，将时间锁定到大脑中另一个位置的正在进行的活动。与科学界分享这一工具有望为同步大脑活动在各种神经系统中的功能意义提供新的、基本的见解，这是目前可用的技术无法获得的。这项技术还可能应用于神经假体和脑刺激系统，以治疗神经和精神疾病。该项目包括：1)开发一种算法，从局部场势中可靠地提取主导振荡分量的瞬时频率和相位，并准确地预测特定相角的下一次出现。2)在硬件和软件的结合中实现算法(S)，其速度足够快，可以实时控制刺激装置。3)在活体内验证闭环刺激技术，并开发其在皮质-皮质和丘脑-皮质通讯研究中的应用。这种系统的成功开发将为测试神经信号计时，特别是同步节律活动的功能意义的理论扫清一个主要障碍。它将允许超越相关的测量，探索人工操纵神经信号的行为(和神经)后果，这取决于当前正在进行的神经活动的时间。在这项技术的帮助下，在理解神经信号的时序在编码和在神经元集合之间传输信息方面的作用方面有望取得重大进展。

Oscillatory activity in the brain has been known for a long time, but its functional significance is still being debated. It has recently been proposed that neural oscillations play an important role in controlling how information flows in the brain and which ensembles of neurons are able to exchange information, allowing the brain to flexibly adjust to varying task demands. While this view has been supported by recordings of brain activity from particular subsystems, a rigorous test of the ideas requires manipulation of brain activity to establish a causal link between synchronized brain activity and neural communication. While experimental techniques for generally suppressing or enhancing neural activity are readily available, addressing this scientific question requires new technology for manipulating neural activity with a precise timing relationship relative to ongoing neural activity. The goal of this research project is to develop a closed-loop stimulation system that can analyze ongoing brain oscillations in real time and that uses the resulting information to trigger neural stimulation. This allows manipulating neural activity time-locked to ongoing activity at another location in the brain. Sharing this tool with the scientific community is expected to provide novel, fundamental insights into the functional significance of synchronized brain activity in a variety of neural systems, which cannot be obtained with currently available technology. The technique might also find application in neural prostheses and brain stimulation systems for the treatment of neurologic and psychiatric disorders. The project involves: 1) Developing an algorithm that reliably extracts instantaneous frequency and phase of a dominant oscillatory component from a local field potential and accurately predicts the next occurrence of particular phase angles. 2) Implementing the algorithm(s) in a combination of software and hardware that is fast enough for real-time control of a stimulation device. 3) Validating the closed-loop stimulation technique in vivo and developing applications for studying cortico-cortical and thalamo-cortical communication. Successful development of such a system would remove a major obstacle for testing theories about the functional significance of the timing of neural signals, in particular synchronized rhythmic activity. It would allow going beyond correlational measures and exploring the behavioral (and neural) consequences of artificial manipulation of neural signals contingent on the timing of currently ongoing neural activity. With the help of this technology, a major advance in understanding the role of the timing of neural signals in coding and transmitting information between ensembles of neurons is expected.