Investigating the neurophysiological basis of circuit-specific laminar rs-fMRI

研究电路特异性层流 rs-fMRI 的神经生理学基础

• 批准号: 10518479
• 负责人: EMERY N BROWN
• 金额: $ 214.12万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10518479
• 关键词: Address; Anesthetics; Animals; Astrocytes; Axon; Bilateral; Biological Markers; Blood Vessels; Brain; Brain Diseases; Brain Injuries; Brain Mapping; Cerebrovascular Disorders; Cerebrovascular system; Cerebrum; Chronic; Clinical; Corpus Callosum; Coupled; Coupling; Diagnostic; Disease; Etiology; Fiber; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hypotension; Impairment; Injury; Lesion; Measures; Mediating; Methods; Mus; Network-based; Neurons; Pathologic; Patients; Pattern; Photometry; Play; Regulation; Resolution; Rest; Role; Scanning; Scheme; Signal Transduction; Source; Specific qualifier value; Specificity; Techniques; Testing; To specify; Translating; Vascular Dementia; Vascular Diseases; Work; awake; base; bioimaging; blood oxygen level dependent; cerebrovascular; diagnostic tool; functional disability; hypoperfusion; imaging biomarker; improved; mouse model; multimodality; nervous system disorder; neurophysiology; neuroregulation; neurovascular; neurovascular coupling; novel; optogenetics; potential biomarker; response; tool; vascular cognitive impairment and dementia; white matter; white matter injury

Resting-state fMRI has emerged as a potential method to identify diagnostic bio-imaging markers of a broad spectrum of neurological disorders by measuring the low-frequency fluctuation (LFF) correlation features of diseased brains. Due to the fMRI signal’s indirect coupling to neuronal activity, a fundamental challenge of rs- fMRI mapping is how to extract the true “functional connectivity” feature across cortices with circuit specificity. Both direct corticocortical connections, e.g. callosal projections, and subcortical neuromodulatory projections can modulate rs-fMRI connectivity with converging effects on neuro-glio-vascular (NGV) interactions. Also, au- tonomic regulation on gliovascular dynamics further confounds rs-fMRI LFF when interpreting the brain dam- age with vascular impairment in various cerebrovascular diseases. We propose to implement line-scanning and single-vessel fMRI methods in a multi-modal platform to dissect laminar and vascular-specific rs-fMRI LFF and decipher NGV signaling underlying rs-fMRI LFF. Here, we will focus on elucidating the transcallosal circuit- based interhemispheric rs-fMRI LFF correlation in the normal and diseased mouse model with hypoperfusion- induced cerebrovascular white matter injury in the corpus callosum. Three aims will be addressed: 1). We will investigate the causal linkage between laminar-specific bilateral LFF and transcallosal projection. Two hypoth- eses will be tested: i). Layer-specific transcallosal projections determine bilateral LFF laminar correlation pat- terns, and ii). Callosal-driven laminar LFF holds distinct oscillation features from brain state-dependent global LFF. 2). We will differentiate the NGV signaling of callosal-specific and global vascular LFF using multi-modal fMRI. Also, we will test two hypotheses: i). Callosal projection neuron-specific oscillation mediates circuit-spe- cific bilateral LFF, and ii). Distinct astrocytic Ca2+ signals coupled to either callosal projection neuronal activity or global neuromodulation contribute to different forms of LFF correlation. 3). We will specify callosal-specific and global vascular LFF in the hypoperfusion-induced white matter injury mouse model. We will test if hy- poperfusion-induced cerebral flow changes alter global vascular LFF and hypoperfusion-induced injury in the corpus callosum leads to altered bilateral rs-fMRI connectivity. This proposal aims to reveal the mechanistic NGV regulation of circuit-specific rs-fMRI LFF and apply novel rs-fMRI methods in the diseased mouse model to set the foundation to translate specific LFF correlation patterns as potential biomarkers of circuit dysfunction or vascular impairment in pathological brains.

静息状态功能磁共振成像已成为一种潜在的方法，以确定诊断生物成像标记物的广泛 通过测量神经系统疾病的低频波动（LFF）相关特征， 病态的大脑由于fMRI信号与神经元活动的间接耦合，rs- 功能磁共振成像映射是如何提取真正的“功能连接”的特点，跨皮层与电路的特异性。 直接的皮质-皮质连接，如胼胝体投射和皮质下神经调节投射 可以调节rs-fMRI连接，对神经胶质血管（NGV）相互作用具有会聚效应。还有，Au- 神经系统对神经胶质血管动力学的调节在解释脑屏障时进一步混淆了rs-fMRI LFF， 各种脑血管疾病的血管损害年龄。我们建议实施行扫描 和单血管功能磁共振成像方法在多模式平台解剖层和血管特异性rs-fMRI LFF 并破译rs-fMRI LFF下的NGV信号。在这里，我们将重点阐述经胼胝体回路- 基于大脑半球间rs-fMRI LFF相关性的正常和低灌注患病小鼠模型， 诱发脑血管胼胝体白色物质损伤。三个目标将被解决：1）。我们将 研究椎板特异性双侧LFF和经胼胝体投射之间的因果关系。两个假设- 将测试环境、社会和经济状况：i）。层特异性经胼胝体投影确定双侧LFF层相关模式 ，和ii）。胼胝体驱动的层流LFF具有与大脑状态依赖的全局LFF不同的振荡特征。 LFF。2）。我们将使用多模态分析来区分胼胝体特异性和全局血管LFF的NGV信号传导。 功能磁共振成像。此外，我们将测试两个假设：i）。胼胝体投射神经元特异性振荡介导的回路-spe- cific bilateral LFF，和ii）.不同的星形胶质细胞Ca 2+信号与胼胝体投射神经元活动耦合 或整体神经调节有助于不同形式的LFF相关性。3）。我们将指定胼胝体特异性 和低灌注诱导的白色物质损伤小鼠模型中的全局血管LFF。我们将测试是否- 灌注后诱导的脑血流变化改变了脑缺血再灌注大鼠的整体血管LFF和低灌注诱导的损伤。 胼胝体导致双侧rs-fMRI连接改变。该提案旨在揭示 NGV对电路特异性rs-fMRI LFF的调控及rs-fMRI新方法在疾病小鼠模型中的应用 为将特定LFF相关模式转化为回路功能障碍的潜在生物标志物奠定基础 或病理性脑血管损伤。