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.

静止状态fMRI已成为一种潜在的方法来识别广泛的诊断生物成像标记 通过测量低频波动（LFF）相关特征，神经系统疾病的频谱 患病的大脑。由于fMRI信号与神经元活动的间接耦合，RS-的基本挑战 fMRI映射是如何在具有电路特异性的皮质上提取真正的“功能连接”功能。 两种直接皮层连接，例如Callosal项目和皮层神经调节项目 可以调节RS-FMRI连接性，对神经 - 基因血管（NGV）相互作用的影响影响。另外，au- 神经血管动力学的统计调节在解释脑大坝时进一步混淆了RS-FMRI LFF 各种脑血管疾病的血管障碍的年龄。我们建议实施线路扫描 在多模式平台中使用层状和血管特异性RS-FMRI LFF的单元素fMRI方法 RS-FMRI LFF的基础上的DETIPHER NGV信号传导。在这里，我们将着重于阐明thrantrocallosal Cource- 在正常小鼠模型中，基于半球间的RS-FMRI LFF相关性，并非灌注不足 - call体诱导脑血管白质损伤。将解决三个目标：1）。我们将 研究层状特异性双侧LFF和触发膜投影之间的因果关系。两个假设 - ESS将进行测试：i）。层特异性的透性项目决定双边LFF层流相关性 Terns和II）。 Callosal驱动的Laminar LFF具有依赖大脑状态的全局的明显振荡特征 LFF。 2）。我们将使用多模式来区分Callosle特异性和全局血管LFF的NGV信号 fMRI。另外，我们将检验两个假设：i）。 callosal投射神经特异性振荡介导了电路旋转 人工双侧LFF和II）。偶联的不同星形胶质细胞CA2+信号与任何一种callosal投影神经元活动 或全球神经调节有助于不同形式的LFF相关性。 3）。我们将指定特定于Calloss的 在灌注灌注诱导的白质损伤小鼠模型中，全球血管LFF。我们将测试是否 Poperfusion引起的大脑流动变化改变了全局血管LFF，并在灌注不足引起的损伤中 call体导致双侧RS-FMRI连接变化。该建议旨在揭示机械 NGV调节电路特异性RS-FMRI LFF，并将新型的RS-FMRI方法应用于解剖的小鼠模型 为了将特定LFF相关模式转化为电路功能障碍的潜在生物标志物的基础 或病理大脑中的血管障碍。