Origins of Spontaneous Hemodynamic Signals in the Awake Brain
Open Access
- Author:
- Winder, Aaron Thomas
- Graduate Program:
- Engineering Science and Mechanics
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 19, 2017
- Committee Members:
- Patrick James Drew, Dissertation Advisor/Co-Advisor
Patrick James Drew, Committee Chair/Co-Chair
Bruce Gluckman, Committee Member
Steven Schiff, Committee Member
Nanyin Zhang, Outside Member - Keywords:
- Neurovascular Coupling
Behavior
Barrel Cortex
Spontaneous Hemodynamics - Abstract:
- Cerebral blood flow is dynamically regulated through signaling from active neural populations. This neurovascular coupling allows the brain to satisfy its metabolic needs and enables the use of non-invasive imaging techniques, such as fMRI, to study brain function through hemodynamic measurements. In particular, hemodynamic fluctuations, which occur in the absence of a task or overt sensory stimulation, are used to infer ongoing local neural activity and study intrinsic functional brain connectivity. However, the neural underpinnings of these spontaneous hemodynamic signals are not clear. We tested how well spontaneous hemodynamic signals correspond to local neural activity by making simultaneous cerebral blood volume (CBV) and electrophysiological measurements from the somatosensory cortex of awake, head-fixed mice during periods of rest, sensory stimulation, and volitional movement. Large spontaneous CBV changes in the absence of sensory input were primarily driven by volitional whisker and body movements, indicating that unmonitored behaviors could contribute to hemodynamic variance in resting state neuroimaging studies. We then quantified neurovascular coupling as the transfer function between measured neural activity and CBV. We showed that the temporal dynamics of the vascular response to increased neural activity were similar across behavioral states. However, individual CBV changes were weakly predictive of the corresponding local neural activity during periods of rest. To discern the origin of resting state CBV, we perturbed local neural activity and observed that spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking, glutamatergic input, and noradrenergic modulation were blocked. These results indicated that spontaneous hemodynamic signals observed in resting-state imaging data reflect a combination of behavior, local neural activity, and putatively non-neural processes.