Weak correlations between hemodynamic signals and ongoing neural activity during the resting state

Abstract

Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest, and during whisker stimulation and volitional whisking. Here we show that neurovascular coupling was similar across states, and large spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input was blocked, and during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes.

Investigating GABA concentrations measured with macromolecule suppressed and unsuppressed MEGA‐PRESS MR spectroscopy and their relationship with BOLD responses in the occipital cortex

“…Intersubject variability may arise within the connection between induced neural activations and the hemodynamic effects of those responses that are then detected in BOLD fMRI. For example, there may be differences in relative stimulus‐induced cerebral blood flow versus oxygen metabolism changes and different contributions of nonneural regulation of hemodynamic changes . Importantly, MRS measurements reflect bulk rather than synaptic GABA concentrations, and so likely also reflect transmitter that influences vascular and metabolic responses through routes other than its influence of neuronal signaling and for which there may be nonlinearities present .…”

“…For example, there may be differences in relative stimulus-induced cerebral blood flow versus oxygen metabolism changes 32 and different contributions of nonneural regulation of hemodynamic changes. 33 Importantly, MRS measurements reflect bulk rather than synaptic GABA concentrations, 34 and so likely also reflect transmitter that influences vascular and metabolic responses through routes other than its influence of neuronal signaling 35,36 and for which there may be nonlinearities present. 37 Previous work has provided evidence for a linear relationship between MRS measures of GABA and nonhemodynamic signatures of neural activity, including EEG and MEG, 38 but these results do not provide clear evidence that the MRS measures are related to stimulusinduced responses rather than reflecting structural properties of the local neural networks.…”

Functional hyperemia drives fluid exchange in the paravascular space

“…To simulate the peristaltic wave due to the heartbeat, the position of the inner wall of the PVS was prescribed via a travelling sinusoidal wave whose amplitude 9 , frequency 23 and velocity 24,25 were taken from experimental observations in mice. When the PVS was of anatomically realistic size (3 µm wide and 250 µm long, see methods) we observed no appreciable unidirectional pumping of fluid (0.75 m 3 /s, 0.0015% volume of PVS per second).…”

“…These pulsations travel at a speed of 0.5-10 m/s along the arterial tree 25,88,89 . Mice have a heartrate of 7-14 Hz when they are awake and freely behaving 23 . Neural activity can drive 10-30% changes in arterial radius.…”

Mouse optical imaging for understanding resting-state functional connectivity in human fMRI

“…Alternatively, the use of anesthetized preparation could have caused non-stationary FC in the mouse data. A recent report using simultaneous measurement of electrophysiological and optical intrinsic signals in local population of mouse somatosensory neurons showed that “spontaneous” hemodynamic activity is driven by behavior (e.g., whisking) and correlate only weakly with neuronal activity [25]. Whether or not such “spontaneous” hemodynamic activity contains spatial patterns relevant to resting-state FC remains unclear.…”