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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

基本信息

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
项目类别：
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

项目摘要

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志物的广泛