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Effects of intrinsic and drug-induced neuromodulation on functional brain imaging

内在和药物诱导的神经调节对功能性脑成像的影响

基本信息

批准号：
10220930
负责人：
Anna Devor
金额：
$ 38.82万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10220930
关键词：
Acetylcholine Acute Affect Animal Model Animals Arousal Attention BRAIN initiative Blood Vessels Brain Brain imaging Brain region Cerebrovascular Circulation Cerebrum Chronic Cocaine Conscious Consumption Decision Making Dilator Dopamine Electrophysiology (science)Energy Metabolism Evaluation Exposure to Foundations Functional Magnetic Resonance Imaging Generations Human Image Imaging technology Individual Intoxication Knowledge Learning Measurable Measurement Measures Mediating Memory Metabolic Microscope Microscopic Modality Mus Neuromodulator Neurons Neurotransmitters Nitric Oxide Norepinephrine Optical reporter Optics Partial Pressure Pharmaceutical Preparations Pharmacology Physiological Property Prostaglandins Psychiatrist Psychologist Pyramidal Cells Reporter Research Rest Rewards Signal Transduction Somatosensory Cortex Substance of Abuse System Testing Time Vasodilation awake base blood oxygen level dependent cocaine exposure cognitive function constriction drug of abuse experimental study foot frontal lobe hemodynamics high resolution imaging human subject imaging study inhibitory neuron metabolic rate neuropeptide Y neuroregulation neurotransmission neurovascular non-invasive imaging optogenetics response tool two photon microscopy two-photon vasoconstriction

项目摘要

Abstract Ascending neuromodulation associated with cognitive functions, such as arousal, attention, learning, memory, decision making, evaluation of reward, are active in any conscious human subject participating in a Blood Oxygenation Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) study. And yet, our understanding of how these systems affect the BOLD signal remains rudimentary. In fact, our current knowledge of neurovascular and neurometaboic mechanisms that underlie the BOLD signal has been derived almost exclusively from studies in anesthetized animals where the state of neuromodulation was uncertain. Recently, we have developed optical reporters for dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) applicable for high-resolution imaging of brain function in awake behaving mice. In the proposed project, we will combine these reporters with an integrated suite of the BRAIN Initiative tools, developed by us and others, to investigate the microscopic makeup of “brain states” and their reflection in macroscopic BOLD fMRI signals. These tools (except fMRI) are only applicable to model organisms. Therefore, all experiments will be performed in awake behaving mice. Our Central Hypothesis is that ascending projections from one or more neuromodulatory systems contribute critically to generation of spontaneous (“resting-state”) hemodynamic fluctuations as well as task-induced hemodynamic responses. To test this hypothesis, we will investigate the relationship between neuronal, vascular and metabolic activity as a function of (i) intrinsic brain states (Aims 1-2), and (ii) exposure to cocaine – a common drug of abuse that acts by affecting neuromodulation (Aim 3). Brain states will be operationally defined based on the readout of DA, NE, and ACh reporters referenced to electrophysiological/imaging measures of local cortical dynamics. These studies will be performed in the context of resting-state hemodynamic fluctuations as well as task-induced hemodynamic responses in the primary somatosensory and frontal cortices. The proposed project will (i) provide a stronger physiological foundation for resting-state and task-induced fMRI in healthy individuals; (ii) place the relationship between the state of neuromodulation and energy expenditure (cerebral metabolic rate of O2, CMRO2) on a quantitative footing; and (iii) examine the effects of cocaine on neuronal and hemodynamic brain activity. This study will also generate further hypotheses about the ways in which substance exposure may affect fMRI readouts.

摘要