The goal of this project is to quantify how natural behaviors modulate hemodynamic signals in the cortex, and to measure their coupling to neural activity. We will concurrently measure neural activity and hemodynamic signals, using electrophysiology, intrinsic optical signal imaging and two-photon laser scanning microscopy, in the cortex of awake, head-fixed mice. Mice will be free to alternate between running, grooming or quiescent behaviors on top of a spherical treadmill. We will use pharmacology to dissect the relative contributions of central neural and peripheral cardiovascular mechanisms in controlling cerebral blood flow. The neurovascular impulse response function, which defines the relationship between neural activity and blood flow, will be quantified across behaviors to test the constancy of neurovascular coupling. Lastly, we will test whether functional networks, areas with correlated blood flow during rest, are similarly correlated during locomotion. Understanding if, and how, the behavioral state modulates the cortical hemodynamic response, the coupling of blood flow to neural activity, and functional connectivity, are all critical for the interpretationof hemodynamic signals.

Public Health Relevance

Changes in cerebral blood flow are coupled to neural activity, and are extensively used to assay brain activity non-invasively. This proposal seeks to understand how these blood flow changes are related to neural activity and behavioral state, which we hope will aid in the diagnosis and treatment of cerebrovascular and cognitive disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (SPC)
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pennsylvania State University
Engineering (All Types)
Schools of Engineering
University Park
United States
Zip Code
Adams, Matthew D; Winder, Aaron T; Blinder, Pablo et al. (2018) The pial vasculature of the mouse develops according to a sensory-independent program. Sci Rep 8:9860
Winder, Aaron T; Echagarruga, Christina; Zhang, Qingguang et al. (2017) Weak correlations between hemodynamic signals and ongoing neural activity during the resting state. Nat Neurosci 20:1761-1769
Gao, Yu-Rong; Ma, Yuncong; Zhang, Qingguang et al. (2017) Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal. Neuroimage 153:382-398
Gao, Yu-Rong; Drew, Patrick J (2016) Effects of Voluntary Locomotion and Calcitonin Gene-Related Peptide on the Dynamics of Single Dural Vessels in Awake Mice. J Neurosci 36:2503-16
Gao, Yu-Rong; Greene, Stephanie E; Drew, Patrick J (2015) Mechanical restriction of intracortical vessel dilation by brain tissue sculpts the hemodynamic response. Neuroimage 115:162-76
Huo, Bing-Xing; Gao, Yu-Rong; Drew, Patrick J (2015) Quantitative separation of arterial and venous cerebral blood volume increases during voluntary locomotion. Neuroimage 105:369-79
Huo, Bing-Xing; Greene, Stephanie E; Drew, Patrick J (2015) Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes. Neuroimage 118:301-12
Shirey, Michael J; Smith, Jared B; Kudlik, D'Anne E et al. (2015) Brief anesthesia, but not voluntary locomotion, significantly alters cortical temperature. J Neurophysiol 114:309-22
Letourneur, Annelise; Chen, Victoria; Waterman, Gar et al. (2014) A method for longitudinal, transcranial imaging of blood flow and remodeling of the cerebral vasculature in postnatal mice. Physiol Rep 2:
Huo, Bing-Xing; Smith, Jared B; Drew, Patrick J (2014) Neurovascular coupling and decoupling in the cortex during voluntary locomotion. J Neurosci 34:10975-81

Showing the most recent 10 out of 11 publications