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经成为一种潜在的方法来识别广泛的 通过测量脑电地形图的低频起伏(LFF)相关特征来研究神经疾病的频谱 脑部疾病。由于fMRI信号与神经元活动的间接耦合，RS的一个根本挑战-- 功能磁共振成像是如何提取具有电路特异性的大脑皮层真正的“功能连通性”特征。 皮质的直接联系，例如膝盖体投射和皮质下神经调节性投射 可以通过对神经-神经胶质-血管(NGV)相互作用的汇聚效应来调节rs-fmri的连接性。另外，Au- 在解释脑损伤时，神经胶质血管动力学的眼压调节进一步混淆了rs-fmri lff。 年龄与各种脑血管疾病的血管损害有关。我们建议实施行扫描 在多模式平台中的单血管fMRI方法来解剖层流和血管特异性的rs-fmri lff 并破译rS-fmri lff背后的NGV信号。在这里，我们将重点阐明跨骨痂环路-- 基于大脑半球间rs-fmri lff相关性的正常和疾病低血流灌注小鼠模型。 脑血管白质损伤所致的胼胝体。将解决三个目标：1)。我们会 研究板层特异性双侧LFF与经颧骨投射之间的因果联系。两个假设- ESES将接受测试：i)。特定层别的经颧骨投射决定了双侧LFF的椎板相关性PAT。 燕鸥，以及ii)。膝盖骨驱动的层流LFF具有不同于大脑状态依赖的整体振荡特征 LFF。2)。我们将使用多模式区分特定的和全局血管LFF的NGV信号 功能磁共振成像。此外，我们还将检验两个假设：i)。膝盖骨投射神经元特异性振荡介导环路特异性振荡 具体的双侧LFf，以及ii)。不同的星形胶质细胞钙信号与胼胝体投射神经元的活动 或者，全球神经调节对不同形式的LFF相关性有贡献。3)。我们将指定特定于膝盖骨的 以及低灌注性脑白质损伤小鼠模型中的全血管LFF。我们会测试他是否- 全脑灌流诱导的脑血流改变改变全脑血管LFF和低灌流诱导的损伤 胼胝体导致双侧RS-fMRI连通性改变。这项提议旨在揭示 NGV对电路特异性rS-fMRI Lff的调节及在疾病小鼠模型中应用新的rS-fMRI方法 为将特定的LFF相关模式转换为回路功能障碍的潜在生物标志物奠定基础 或病理性大脑中的血管损伤。