Examining the Effects of Suppression of Slow Rhythms on Resting State fMRI

检查慢节律抑制对静息态 fMRI 的影响

• 批准号: 10373750
• 负责人: Kaundinya Srinivasan Gopinath
• 金额: $ 43.04万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-29 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373750
• 关键词: Area; Arousal; Bilateral; Biological Markers; Brain; Brain Pathology; Brain imaging; Brain region; Calcium; Cognition; Cognitive; Coupled; Data; Dexmedetomidine; Dimethyl Sulfoxide; Disease; Dose; Electroencephalography; Exhibits; Forelimb; Frequencies; Functional Magnetic Resonance Imaging; Human; Imaging Techniques; Impairment; Injections; Knowledge; Maintenance; Measurement; Measures; Methods; Pathology; Pattern; Performance; Periodicity; Pharmaceutical Preparations; Production; Property; Rattus; Rest; Rodent; Rodent Model; Role; Saline; Scanning; Sedation procedure; Seeds; Sensory; Signal Transduction; Source; Specificity; Structure; Subcutaneous Injections; T-Type Calcium Channels; Testing; Time; base; blood oxygen level dependent; brain disorder diagnosis; channel blockers; cohort; experimental study; functional disability; human subject; imaging study; interest; multimodality; neurophysiology; relating to nervous system; signal processing; somatosensory; subcutaneous; tool; vigilance

PROJECT SUMMARY/ABSTRACT Blood oxygenation level dependent (BOLD) resting state fMRI (rsfMRI) has become the preeminent tool for exploring brain function and pathology. However, the neurophysiological basis of rsfMRI signals is not fully understood, impeding comprehensive interpretations of these studies. Recently, brain slow rhythms have been put forth as possible sources of rsfMRI signal. RsfMRI signals are characterized by presence of transient quasiperiodic patterns (QPPs), which are often not specific any canonical brain function networks (e.g., those that subserve cognition). QPPs confound the estimation of accurate brain functional connectivity (FC) in canonical brain function networks. These transient signals share a number of properties with cortical slow rhythms. They exist in the absence of stimulation, propagate across the cortex, and are strongly modulated by vigilance, similar to slow waves. It is possible that only these components QPPs, and not rsfMRI signal specific to FC in canonical brain function networks are driven by slow rhythms. One mechanism for expression and maintenance of cortical slow rhythms in the brain is through a thalamocortical network of coupled oscillators driven by burst firing induced by low-threshold T-type calcium (Ca2+) channels. Systemic administration of the selective T-type Ca2+ channel blocker (TTCCB) TTA-P2 suppresses slow brain rhythms (i.e., decrease the number of slow waves observed in a given time window) by up to 60% in rats. In this study, we will examine the effects of suppression of slow waves on rsfMRI signals. We hypothesize that suppression of slow rhythms will reduce the strength of QPPs. And this reduction in expression of QPPs will enhance the specificity of FC in canonical brain function network. We will acquire simultaneous rsfMRI and EEG data from a group of 25 rats 90 min before and 90 minutes after subcutaneous injection of the drug TTA-P2 at an optimal dose to be determined on a separate cohort of 20 rats. Another group of 15 rats will receive the vehicle as control. The strength and frequency of expression of QPPs will be estimated under pre- (Baseline) and post-TTA-P2 (or Vehicle) conditions. We will estimate FC in different canonical brain function networks through seed-based cross-correlation analysis with a priori regions of interest specific to each network examined. Differences in QPP metrics, and FC in brain function networks between different conditions will be examined with appropriate hypotheses tests. We expect QPP metrics to be significantly reduced from Baseline after slow wave suppression post-TTA-P2. FC in canonical brain function networks will increase, and non-specific correlations between unconnected brain regions will decrease from baseline post-TTA-P2, thereby increasing the specificity of FC in canonical brain function networks. No significant differences in rsfMRI signal metrics will be observed between Baseline and Vehicle conditions. Successful completion of this project will go a long way towards resolving profound questions regarding the neural basis of rsfMRI signals.

项目总结/摘要 血氧水平依赖性（BOLD）静息态功能磁共振成像（rsfMRI）已成为一种卓越的工具， 探索大脑功能和病理学然而，rsfMRI信号的神经生理学基础并不完全是 这阻碍了对这些研究的全面解释。最近，大脑缓慢的节奏已经 作为rsfMRI信号的可能来源。RsfMRI信号的特征在于存在瞬态 准周期模式（QPP），其通常不是特定于任何典型的脑功能网络（例如，那些 这有助于认知）。QPP混淆了准确的脑功能连接（FC）的估计， 典型的脑功能网络这些瞬态信号与皮层慢波信号有许多共同的特性， 节奏它们在没有刺激的情况下存在，在大脑皮层传播，并受到 警惕，类似于慢波。可能只有这些成分是QPP，而不是rsfMRI信号特异性的 在典型的脑功能网络中，FC是由慢节奏驱动的。一种表达机制， 大脑皮层慢节律的维持是通过丘脑皮层耦合振荡器网络实现的 由低阈值T型钙（Ca2+）通道诱导的爆发放电驱动。全身施用 选择性T型Ca2+通道阻断剂（TTCCB）TTA-P2抑制慢脑节律（即，降低 在给定的时间窗内观察到的慢波数量）在大鼠中高达60%。在这项研究中，我们将研究 慢波抑制对rsfMRI信号的影响。我们假设抑制慢节奏 会降低QPP的强度。这种QPP表达的减少将增强FC在肿瘤中的特异性。 典型脑功能网络 我们将从一组25只大鼠中同时采集rsfMRI和EEG数据，分别在注射前90分钟和注射后90分钟采集 皮下注射药物TTA-P2，最佳剂量有待在20人的单独队列中确定 大鼠另一组15只大鼠将接受溶媒作为对照。表达的强度和频率 将在TTA-P2（或溶剂）前（基线）和后条件下估计QPP。我们将估算FC， 通过基于种子的互相关分析与先验区域的不同典型脑功能网络 具体到每个网络检查的兴趣。脑功能网络中QPP指标和FC的差异 不同条件之间的差异将通过适当的假设检验进行检验。我们预计QPP指标将 TTA-P2后慢波抑制后较基线显著降低。典型脑功能中的FC 网络将增加，未连接的大脑区域之间的非特异性相关性将减少， TTA-P2后基线，从而增加FC在典型脑功能网络中的特异性。没有 在基线和载体条件之间将观察到rsfMRI信号度量的显著差异。 成功完成这一项目将大大有助于解决有关 rsfMRI信号的神经基础。