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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS078168-02
Application #
8628885
Study Section
Special Emphasis Panel (SPC)
Program Officer
Babcock, Debra J
Project Start
2013-03-01
Project End
2018-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
$286,861
Indirect Cost
$89,986
Name
Pennsylvania State University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Gao, Yu-Rong; Drew, Patrick J (2014) Determination of vessel cross-sectional area by thresholding in Radon space. J Cereb Blood Flow Metab 34:1180-7
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