title: High-speed vascular dynamics of the hemodynamic response.
abstract: While a range of cellular mechanisms have been proposed to underlie control of neurovascular coupling, a comprehensive, reconciliatory model has yet to be determined. To fit with such a model, it is essential that candidate mechanisms exhibit reaction times, spatial ranges, and speeds of propagation that are consistent with the vascular manifestations of the 'hemodynamic response'. Understanding these vascular dynamics is therefore a critical step towards developing a robust model of neurovascular coupling. In this study, we utilize high-speed optical imaging of exposed rodent somatosensory cortex to explore and characterize the spatiotemporal dynamics of surface vessels during functional hyperemia. Our high-speed, high-resolution optical imaging approach allows us to study the hemodynamic response independently in individual vessels, and in discrete regions of the parenchyma with enough resolution to precisely characterize subtle spatial and temporal features of the response. Specifically, we explore when and where the first hemodynamic changes occur in response to stimuli, the direction and speed at which these changes propagate in arterioles and regions of the parenchyma, and the relative timing at which each of these compartments returns to its original baseline state. From these results, we are able to conclude that the hemodynamic response appears to initiate in the parenchyma and then spreads rapidly to surface arterioles. Following the initial onset we find evidence that the response spreads spatially outwards via the dilation of targeted arterioles. This propagation of vasodilation is independent of the direction of blood flow within each arteriole. We also find evidence of a decay phase that acts with a more uniform spatial dependence, rather than along targeted vessels, causing the periphery of the responding region to return to baseline first. We hypothesize that different underlying cellular mechanisms/signaling pathways are responsible for the response initiation and the response decay. Our results advance the fundamental understanding of the hemodynamic response, as well as our ability to evaluate potential cellular mechanisms for their involvement in neurovascular coupling.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA. bc2288@columbia.edu
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Chen
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Bouchard
authors.forename: Addason F H
authors.initials: AF
authors.lastname: McCaslin
authors.forename: Sean A
authors.initials: SA
authors.lastname: Burgess
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Hillman
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D021621:Imaging, Three-Dimensional / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000502:physiology*; D013997:Time Factors