title: Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons.
abstract: Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Shaik
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032.
authors.forename: Mariel G
authors.initials: MG
authors.lastname: Kozberg
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027.
authors.forename: Sharon H
authors.identifier: 0000-0002-5044-5177
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Portes
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Timerman
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027; eh2245@columbia.edu.|Department of Radiology, Columbia University, New York, NY 10032.|Kavli Institute for Brain Science, Columbia University, New York, NY 10032.|Mortimer B. Zuckerman Institute for Mind Brain and Behavior, Columbia University, New York, NY 10032.
authors.forename: Elizabeth M C
authors.identifier: 0000-0001-5511-1451
authors.initials: EM
authors.lastname: Hillman
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D003344:Cortical Synchronization; D055724:Electrophysiological Phenomena; D005456:Fluorescent Dyes / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006439:Hemodynamics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008959:Models, Neurological; D009415:Nerve Net; D009474:Neurons / Q000502:physiology*; D061848:Optical Imaging; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins
keywords: GCaMP; neural network activity; neurovascular coupling; optical imaging; resting state