Defining Neuronal Circuits and Cellular Processes Underlying Resting fMRI Signals

定义静息 fMRI 信号下的神经元回路和细胞过程

• 批准号: 9206010
• 负责人: Michael Peter Milham
• 金额: $ 96.21万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-22 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9206010
• 关键词: Activity Cycles; Anatomy; Architecture; Area; Brain; Cell physiology; Cells; Clinical; Complex; Computing Methodologies; Coupled; Coupling; Data; Electric Stimulation; Electrodes; Electroencephalography; Electrophysiology (science); Employee Strikes; Epilepsy; Face; Frequencies; Functional Magnetic Resonance Imaging; Goals; Hand; Human; Link; Maps; Measures; Mental Health; Metabolic; Methods; Microscopic; Modeling; Monkeys; Neurons; Neurosciences; Nodal; Operative Surgical Procedures; Patients; Pattern; Phase; Population; Process; Property; Reproducibility; Reproducibility of Results; Research; Rest; Role; Scalp structure; Signal Transduction; Source; Specific qualifier value; System; Task Performances; Testing; Variant; Work; biomarker discovery; blood oxygen level dependent; density; electric field; indexing; innovation; interest; neural circuit; neuromechanism; neuronal circuitry; neuronal patterning; neurophysiology; neuroregulation; novel; relating to nervous system; Activity Cycles; Anatomy; Architecture; Area; Brain; Cell physiology; Cells; Clinical; Complex; Computing Methodologies; Coupled; Coupling; Data; Electric Stimulation; Electrodes; Electroencephalography; Electrophysiology (science); Employee Strikes; Epilepsy; Face; Frequencies; Functional Magnetic Resonance Imaging; Goals; Hand; Human; Link; Maps; Measures; Mental Health; Metabolic; Methods; Microscopic; Modeling; Monkeys; Neurons; Neurosciences; Nodal; Operative Surgical Procedures; Patients; Pattern; Phase; Population; Process; Property; Reproducibility; Reproducibility of Results; Research; Rest; Role; Scalp structure; Signal Transduction; Source; Specific qualifier value; System; Task Performances; Testing; Variant; Work; biomarker discovery; blood oxygen level dependent; density; electric field; indexing; innovation; interest; neural circuit; neuromechanism; neuronal circuitry; neuronal patterning; neurophysiology; neuroregulation; novel; relating to nervous system

Intrinsic ‘functional connectivity’ (iFC), a measure of correlation between spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal, reliably distinguish networks of cortical and subcortical areas during both rest and active task performance. iFC methods can map the functional architecture of the human brain in both healthy and pathological conditions, in high detail using as little as 5 minutes of data. Striking reproducibility and test-retest reliability of findings across centers have fueled a widespread application of iFC measures in clinical neuroscience, biomarker discovery, and human connectomics. However, the neural circuits and cellular processes underlying BOLD-iFC remain poorly specified. BOLD amplitude itself appears related to neural activity in the high gamma (HG) range (~70-200 Hz), and thus to an extent, with neuronal firing. However, BOLD’s relationship to the lower frequencies is controversial. This is a critical disconnect, as oscillatory activities below 40Hz reflect ongoing cell-circuit excitability fluctuations that control neuronal firing; i.e., the amplitude of neural population firing is “coupled” to oscillatory phase. In this, the simplest form of such phase-amplitude coupling (PAC), amplitude variations in higher frequency activity (e.g., firing or HG) are coupled to the phase of a lower frequency (e.g., theta). PAC operates both pairwise and recursively over the spectrum, from the range of neuronal firing down to the slow/infraslow (<1Hz) range where BOLD amplitude fluctuations are observed using resting state fMRI (R-fMRI). Thus PAC may provide a key to connecting resting BOLD fluctuations to activity cycles in the underlying cell circuits. In our framework: 1) At a microscopic, cortical cell-circuit level, a complex of excitatory and inhibitory interactions between neurons generate rhythmic excitability fluctuations (oscillations). 2) PAC organizes slow (0.5-12) Hz and mid-range (13-40Hz) oscillations hierarchically, ultimately controlling temporal patterns of neuronal firing. 3) Infraslow (0.01-0.1 Hz) neural activity fluctuations synchronize to form the macroscale intrinsic connectivity networks (ICN) indexed by R- fMRI, and use PAC to orchestrate faster activity within a network. Our broad goal is to use integrated human and monkey studies to investigate the relationship between macroscale BOLD-derived iFC patterns, and their underlying mechanisms at the microscale cell-circuit level. We will study the sensorimotor network, as its “nodal” organization and other properties are well understood, and it shows good human-simian correspondence. Focusing on key nodes in this network (e.g., face and hand areas), we will recapitulate prior work tying R-FMRI iFC to macroscale scalp EEG and mesoscale stereotactic (S)-EEG, and will use innovative laminar multielectrode methods to establish novel links to the cell circuit level. Established modeling and computational methods will help to construct a comprehensive model that connects macroscale iFC to underlying microscale, cell circuit activity.

固有的“功能连通性”（IFC），血液中赞的波动之间相关性的量度 氧气依赖性（粗体）信号，可靠地区分皮质和皮质下区域的网络 休息和主动任务性能。 IFC方法可以绘制人脑的功能架构 健康和病理状况，详细使用只有5分钟的数据。引人注目 各个中心发现的可重复性和重测的可靠性已为IFC提供了宽度的应用 临床神经科学，生物标志物发现和人类连接组学的措施。但是，神经元 大胆IFC的基础电路和细胞过程的指定仍然很差。大胆的放大器本身出现 与高γ（Hg）范围（〜70-200 Hz）中的神经元活性有关，因此在一定程度上与神经元有关 射击。但是，Bold与较低频率的关系是有争议的。这是关键的断开连接 低于40Hz以下的振荡活动反映了控制神经元发射的持续的细胞电路兴奋性波动； 即，神经种群射击的放大器与振荡阶段“耦合”。在这种情况下，最简单的形式 相位振幅耦合（PAC），较高频率活性（例如，发射或Hg）的放大器变化为 耦合到较低频率的相位（例如，theta）。 PAC在 频谱，从神经元的射击范围向下到慢速/infraslow（<1Hz）范围 使用静息状态fMRI（R-FMRI）观察到波动。 PAC可能会提供连接休息的关键 基础细胞回路中的活性循环的大胆波动。在我们的框架中：1）在显微镜下， 皮质细胞电路水平，神经元之间的兴奋和抑制作用的复合物会产生节奏 兴奋性波动（振荡）。 2）PAC组织缓慢（0.5-12）Hz和中端（13-40Hz）振荡 从层次上讲，最终控制神经元射击的临时模式。 3）Infraslow（0.01-0.1 Hz）神经元 活性波动同步以形成由R-索引的宏观内在连通网络（ICN） fMRI，并使用PAC在网络中进行更快的活动来安排活动。我们的广泛目标是使用综合的人 和猴子研究以调查宏观衍生的IFC模式及其之间的关系 微观细胞电路水平的基本机制。我们将研究感觉运动网络，因为 “节点”组织和其他属性已被充分理解，它显示了良好的人类西米安 一致。关注该网络中的关键节点（例如面部和手部区域），我们将概括 将R-FMRI IFC与宏观SCACP EEG和中尺度立体定向（S）-eeg联系起来的工作，并将使用创新 层流多电极方法建立了与细胞电路水平的新链接。建立的建模和 计算方法将有助于构建一个将宏观IFC连接到的综合模型 基础显微镜，细胞电路活性。