Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes.

Understanding how changes in the cardiovascular system contribute to cerebral blood flow (CBF) and volume (CBV) increases is critical for interpreting hemodynamic signals. Here we investigated how systemic cardiovascular changes affect the cortical hemodynamic response during voluntary locomotion. In the mouse, voluntary locomotion drives an increase in cortical CBF and arterial CBV that is localized to the forelimb/hindlimb representation in the somatosensory cortex, as well as a diffuse venous CBV increase. To determine if the heart rate increases that accompany locomotion contribute to locomotion-induced CBV and CBF increases, we occluded heart rate increases with the muscarinic cholinergic receptor antagonist glycopyrrolate, and reduced heart rate with the β1-adrenergic receptor antagonist atenolol. We quantified the effects of these cardiovascular manipulations on CBV and CBF dynamics by comparing the hemodynamic response functions (HRF) to locomotion across these conditions. Neither the CBF HRF nor the arterial component of the CBV HRF was significantly affected by pharmacological disruption of the heart rate. In contrast, the amplitude and spatial extent of the venous component of the CBV HRF were decreased by atenolol. These results suggest that the increase in venous CBV during locomotion was partially driven by peripheral cardiovascular changes, whereas CBF and arterial CBV increases associated with locomotion reflect central processes.