Measuring, Modeling, and Modulating Cross-Frequency Coupling

跨频耦合的测量、建模和调制

• 批准号: 9789298
• 负责人: Uri Tzvi Eden
• 金额: $ 33.09万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789298
• 关键词: Address; Alpha Rhythm; Biological; Biophysics; Brain; Brain region; Clinical; Communication; Communities; Complex; Computer Simulation; Computer software; Coupled; Coupling; Data; Data Analyses; Distant; Electric Stimulation; Emotions; Engineering; Ensure; Experimental Designs; Frequencies; Functional disorder; Generations; Individual; Interdisciplinary Study; Intuition; Label; Learning; Linear Models; Link; Measures; Methods; Modeling; Neurons; Neurosciences; Performance; Periodicity; Phase; Population Dynamics; Procedures; Psychiatrist; Rattus; Research; Research Personnel; Role; Short-Term Memory; Structure; Synapses; System; Testing; Time; Validation; Variant; Work; brain electrical activity; experimental study; flexibility; in vivo; innovation; insight; interest; neural circuit; particle; predictive modeling; relating to nervous system; simulation; statistics; time use; tool; voltage

PROJECT SUMMARY Although rhythms are a prominent feature of brain activity, the role of rhythms in brain function (and dysfunction) remains elusive. Rhythms have been proposed to organize information transfer within and between brain regions by modulating neural excitability at different time scales. Rhythms have also been proposed to interact across these different time scales, a phenomenon labeled cross-frequency coupling or CFC. Clinical and experimental observations have identified many different types of CFC, such as coupling between the phase of a low frequency rhythm and the amplitude of a high frequency rhythm (phase-amplitude coupling), or between the phases of two different frequency rhythms (phase-phase coupling). Many functional roles for CFC have been proposed, including in working memory, neuronal computation, communication, learning and emotion. Despite the mounting experimental evidence for CFC, three important challenges remain that limit understanding of this phenomenon. First, many different data analysis methods have been developed to characterize CFC, with each method typically focused on one type of CFC. Choosing an inappropriate method weakens statistical power and introduces opportunities for confounding effects. Second, analysis of CFC typically occurs post hoc, prohibiting opportunities to modulate CFC during an experiment. New methods are needed to assess CFC in real time while limiting the impacts of potential confounds. Third, the mechanisms that produce CFC are not known. While computational models developed to explore these mechanisms provide important insights, these models have been mainly restricted to synaptic mechanisms of rhythm generation and associations between two types of rhythms. New models are needed to examine the role of other rhythms and rhythm generating mechanisms in CFC. Inclusion of more realistic biological features in simulations of neural rhythms facilitates exploration of a new challenge: how electrical stimulation modulates CFC. In this project, an interdisciplinary research group consisting of a statistician, a mathematician, and a psychiatrist-engineer will analyze, model, and modulate cross-frequency coupling. To do so, the team will develop and apply a statistical inference framework suitable for real time analysis of CFC, and apply this framework to analyze - and modulate with electrical stimulation - in vivo recordings from rat cortex and subcortex. The team will also develop computational models of CFC, to link the observed data to cellular mechanisms, and create hypotheses testable in the in vivo experiments. Completion of the proposed research will represent a significant step forward toward a more complete understanding of cross-frequency coupling, and toward a system for exploring and testing innovative methods for its modulation.

项目概要 尽管节律是大脑活动的一个显着特征，但节律在大脑功能中的作用（和 功能障碍）仍然难以捉摸。已提出节奏来组织内部和内部的信息传递 通过在不同时间尺度调节神经兴奋性来调节大脑区域之间的关系。节奏也已 建议在这些不同的时间尺度上相互作用，这种现象被标记为交叉频率耦合或 氟氯化碳。临床和实验观察已经确定了许多不同类型的 CFC，例如耦合 低频节律的相位与高频节律的幅度之间（相位-幅度 耦合），或两个不同频率节律的相位之间（相间耦合）。功能多 人们已经提出了 CFC 的作用，包括工作记忆、神经元计算、通信、 学习和情感。尽管 CFC 的实验证据越来越多，但仍面临三个重要挑战 仍然限制了对这一现象的理解。首先，我们采用了多种不同的数据分析方法。 开发用于表征 CFC，每种方法通常侧重于一种类型的 CFC。选择一个 不适当的方法会削弱统计能力并带来产生混杂效应的机会。第二， CFC 的分析通常发生在事后，从而禁止在实验期间调节 CFC。 需要新的方法来实时评估 CFC，同时限制潜在混杂因素的影响。第三， 产生 CFC 的机制尚不清楚。虽然开发了计算模型来探索这些 机制提供了重要的见解，这些模型主要限于突触机制 节奏的产生以及两种节奏之间的关联。需要新的模型来检验 其他节律和节律生成机制在 CFC 中的作用。包含更真实的生物 神经节律模拟的特征有助于探索新的挑战：电刺激如何 调节 CFC。在这个项目中，一个跨学科研究小组由一名统计学家、一名 数学家和精神病学家工程师将分析、建模和调制交叉频率耦合。到 为此，该团队将开发并应用适合 CFC 实时分析的统计推断框架， 并应用该框架来分析并通过电刺激进行调节大鼠体内记录 皮层和皮层下。该团队还将开发 CFC 的计算模型，将观察到的数据与 细胞机制，并创建可在体内实验中检验的假设。完成拟议的 研究将代表朝着更全面地理解交叉频率迈出的重要一步 耦合，以及探索和测试其调制创新方法的系统。