CRCNS: Advancing Computational Methods to Reveal Human Thalamocortical Dynamics

CRCNS：推进计算方法来揭示人类丘脑皮质动力学

• 批准号: 9120937
• 负责人: MATTI HAMALAINEN
• 金额: $ 29.18万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9120937
• 关键词: Area; Basal Ganglia; Biology; Boston; Brain; Budgets; Characteristics; Computer Simulation; Computer software; Computing Methodologies; Data; Deep Brain Stimulation; Disease; Educational Curriculum; Electroencephalography; Electrophysiology (science); Essential Tremor; Event; Frequencies; Generations; Head; Health; High School Student; Human; Image; Investigation; Magnetic Resonance Imaging; Mathematics; Measures; Methods; Modeling; Motor; Neurosciences; Operative Surgical Procedures; Patients; Process; Signal Transduction; Source; Stimulus; Structure; Students; Synapses; Tactile; Testing; Thalamic structure; Time; Tremor; Work; base; curriculum enhancement; experience; high school; insight; mathematical model; median nerve; millisecond; model development; neural model; novel; open source; outreach program; programs; relating to nervous system; response; sensorimotor system

DESCRIPTION (provided by applicant): Advancing methods to image and interpret neural activity in humans on fine temporal-spatial scales is critical to understanding how the brain works in health and disease. Magneto-/Electroencephalography (M/EEG) combined with structural MRI provides reliable recordings of cortical activity with millisecond precision. Recordings from subcortical structures, such as thalamus, have been limited due to low signal amplitudes and inherent difficulty in source localization. Further, our understanding of the generation of the macroscopic electrical currents producing these signals from cellular events is lacking. We will integrate M/EEG, computational modeling, and invasive electrophysiological recordings in human patients to optimize M/EEG inverse solvers to localize distributed thalamocortical (TC) sources and to interpret the underlying cellular events. To optimize our methods we will employ two paradigms known to robustly activate distinct thalamic and cortical sources in the sensorimotor system, including thalamus, SI, MI, SII: (1) median nerve (MN) evoked responses, & (2) motor evoked tremor activity in Essential Tremor (ET) patients. Our M/EEG inverse methods will take advantage of the fact low frequency (LF <100Hz) and high frequency (HF 100-800hz) evoked responses are disjoint in space and time and will combine this characteristic with precise anatomical head modeling constraints to localize concurrent cortical and thalamic activities. To interpret the cellular level events underlying the signals, we will expand a previously developed neural model of TC circuitry that accurately simulates LF SI tactile evoked source waveforms up to 125ms post-stimulus based on sequences of synaptic drive from thalamus and cortex. This model will be expanded to interpret the origin of observed LF and HF activity in the distributed TC network. Results will be validated and informed with invasive electrophysiological recording in ET patients undergoing deep brain stimulation (DBS) surgery. AIM 1: ADVANCE M/EEG TIME-FREQUENCY BASED INVERSE SOLVERS TO LOCALIZE TC EVOKED LF & HF ACTIVITY. We will establish that our advanced inverse methods can reliably localize sources in the thalamus, SI, MI, and SII, during (a) MN stimulation in healthy subjects & (b) MN and motor evoked tremor activity in ET patient, and that the responses from these sources are reflected in a sequence of LF and HF activities. AIM 2: INTERPRET CELLULAR LEVEL ORIGIN OF LF & HF SOURCE ACTIVITY WITH NEURAL MODELING. We will expand an existing computational model of a SI circuit that accurately simulates tactile evoked M/EEG measured source activity to an interconnected thalamic, SI, MI, and SII network. We will test the hypotheses that synaptic interactions between the networks can reproduce the sequences of activity measured Aim 1 and that the HF activity is created by burst firing, while the LF events represent initial synaptically driven slow dendriti processes and the envelope of the HF bursts. AIM 3: VALIDATE INVERSE METHODS AND MODEL PREDICTIONS WITH INVASIVE TC RECORDINGS. We will record LFP and spiking activity from the thalamus, and ECoG from the sensorimotor cortex, of ET patients undergoing DBS surgery during (a) MN stimulation & (b) motor evoked tremor activity. We will use the data to validate Aim 1 source localizations and Aim 2 model predictions. Data will also refine model development and hypotheses. Our integrated approach will provide novel insight into distributed TC activity that is not possible wih one method alone. We will develop free open source softwares that advance the ability to non-invasively (1) study TC interactions in humans with M/EEG & (2) interpret the cellular level origin of the activity. While our investigation is focused on the sensorimotor system, our methods will be broadly applicable to study activity in other brain networks, including deep structures like basal ganglia, and in many experimental paradigms. We will initiate a High School Neuroscience Outreach Program to educate Boston area High School students on human imaging and mathematical modeling in neuroscience. We will target local districts experiencing large budget cuts with elimination in extra-curricular enrichment. Our program will add a complimentary component to the math and biology curriculums.

描述（由申请人提供）：在精细的时空尺度上成像和解释人类神经活动的先进方法对于理解大脑在健康和疾病中如何工作至关重要。磁/脑电图（M/EEG）结合结构MRI提供了可靠的记录皮层活动的毫秒精度。由于低信号幅度和源定位的固有困难，来自皮层下结构（如丘脑）的记录受到限制。此外，我们对从细胞事件产生这些信号的宏观电流的产生缺乏理解。我们将整合M/EEG，计算建模，并在人类患者的侵入性电生理记录，以优化M/EEG逆解算器本地化分布式丘脑皮质（TC）源，并解释潜在的细胞事件。为了优化我们的方法，我们将采用已知的两种范例来稳健地激活感觉运动系统中的不同丘脑和皮质源，包括丘脑、SI、MI、SII：（1）正中神经（MN）诱发的反应，以及（2）特发性震颤（ET）患者中的运动诱发的震颤活动。我们的M/EEG逆方法将利用低频（LF <100 Hz）和高频（HF 100- 800 Hz）诱发反应在空间和时间上不相交的事实，并且将联合收割机将该特性与精确的解剖头部建模约束相结合，以定位并发的皮层和丘脑活动。为了解释信号背后的细胞水平事件，我们 将扩展先前开发的TC电路的神经模型，该模型基于丘脑和皮层的突触驱动序列，精确模拟LF SI触觉诱发源波形长达125 ms的刺激后。这个模型将被扩展，以解释在分布式TC网络中观测到的LF和HF活动的起源。将在接受脑深部电刺激（DBS）手术的ET患者中通过有创电生理记录确认和告知结果。 目的1：改进M/EEG基于时间-频率的逆解器，以定位TC诱发的LF和HF活动。我们将建立我们的先进的反向方法可以可靠地定位源在丘脑，SI，MI，和SII，在（a）MN刺激在健康受试者和（B）MN和运动诱发震颤活动在ET患者，这些来源的反应反映在一系列的LF和HF活动。 目的2：用神经元模型解释LF和HF源活动的细胞水平起源。我们将扩展现有的SI电路的计算模型，准确地模拟触觉诱发M/EEG测量源活动的互连丘脑，SI，MI和SII网络。我们将测试的假设，网络之间的突触相互作用可以重现的活动测量目标1的序列，HF活动是由突发射击，而LF事件表示初始的突触驱动的缓慢dendriti过程和信封的HF突发。 目的3：用侵入性TC记录验证反演方法和模型预测。我们将记录接受DBS手术的ET患者在（a）MN刺激和（B）运动诱发震颤活动期间来自丘脑的LFP和尖峰活动以及来自感觉运动皮层的ECoG。我们将使用这些数据来验证Aim 1源定位和Aim 2模型预测。数据还将完善模型开发和假设。我们的综合方法将提供新的洞察分布式TC活动，这是不可能的单独使用一种方法。我们将开发免费的开源软件，以提高非侵入性的能力（1）研究TC在人类与M/EEG的相互作用&（2）解释细胞水平的起源 的活动。虽然我们的研究重点是感觉运动系统，但我们的方法将广泛适用于研究其他大脑网络的活动，包括基底神经节等深层结构，以及许多实验范式。我们将启动一个高中神经科学外展计划，教育波士顿地区的高中学生在神经科学中的人体成像和数学建模。我们将针对那些预算大幅削减的地方，取消课外活动。我们的计划将增加一个免费的组成部分，数学和生物课程。