Hemodynamic signals allow us to non-invasively assay neural activity and could provide great insight into neural changes during postnatal development. However, it is not clearly understood how neural activity is related to changes in blood flow and oxygenation in the neonatal and juvenile brain. Previous studies in anesthetized animals and sedated humans have come to conflicting results as to the sign and magnitude of neurovascular coupling, and this unresolved issue has stalled the use of hemodynamic imaging in infants and children. In this proposal, we will determine how neurovascular coupling changes during postnatal development in the somatosensory cortex of the awake mouse brain, how this change in neurovascular coupling impacts BOLD fMRI signals, and how behavioral state can alter neurovascular coupling. We will use a multimodal approach, combining optical imaging (intrinsic optical signal imaging and 2-photon microscopy), electrophysiology, and fMRI to elucidate the relationship of hemodynamic signals to neural activity from the levels of single vessels up to the whole brain. We will mechanistically dissect the roles of local neural activity and cardiovascular effects on hemodynamic signals. The research proposed here will enable the use of hemodynamic imaging to study neural activity, plasticity, and neurodevelopmental disorders in infants and juvenile humans and animals.

Public Health Relevance

Hemodynamic signals can give us valuable insight into brain activity and cognitive function. However, the use of hemodynamic signals in infants and juveniles is hampered by our poor understanding of their coupling to neural activity in the awake brain. Here, we will measure neural activity and hemodynamic signals at the level of single vessels up to the entire brain to better understand how neural activity in the developing brains of infants and juveniles are related to hemodynamic signals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS101353-01A1
Application #
9444108
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Babcock, Debra J
Project Start
2017-09-25
Project End
2022-06-30
Budget Start
2017-09-25
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Ma, Zilu; Ma, Yuncong; Zhang, Nanyin (2018) Development of brain-wide connectivity architecture in awake rats. Neuroimage 176:380-389
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