Neurovascular coupling: motive unknown

Abstract

In the brain, increases in neural activity drive changes in local blood flow via neurovascular coupling. The common explanation for increased blood flow (known as functional hyperemia) is that it supplies the metabolic needs of active neurons. However, there is a large body of evidence that is inconsistent with this idea. Baseline blood flow is adequate to supply oxygen needs even with elevated neural activity. Neurovascular coupling is irregular, absent, or inverted in many brain regions, behavioral states, and conditions. Increases in respiration can increase brain oxygenation without flow changes. Simulations show that given the architecture of the brain vasculature, areas of low blood flow are inescapable and cannot be removed by functional hyperemia. As discussed in this article, potential alternative functions of neurovascular coupling include supplying oxygen for neuromodulator synthesis, brain temperature regulation, signaling to neurons, stabilizing and optimizing the cerebral vascular structure, accommodating the non-Newtonian nature of blood, and driving the production and circulation of cerebrospinal fluid (CSF).

Keywords: brain metabolism; cerebral blood flow; cerebrospinal fluid; hypoxia; neuromodulator synthesis; red blood cells.

Figure 1.

Examples of non-canonical neurovascular coupling. A) Canonical neurovascular coupling, with a brief increase in neural activity followed by a slower vasodilation and flow increase. B & C) Inversion of neurovascular coupling in hypothalamus [30] and striatum [22]. D) In the olfactory bulb, there are flow increases in areas without neural activity, but nearby activated areas [27]. E) In the frontal cortex, neural activity goes up during locomotion, but there is a slight decrease in blood volume/flow [–25].

Figure 2.

Potential non-metabolic functions for neurovascular coupling A) Circulation of CSF in the sub-arachnoid space is driven by arterial dilation [97]. B) Arterial dilation can drive convective transport through the brain [100]. C) Elevated pressure drives increased CSF secretion by vasculature [102]. D) Signaling from vasculature to neurons [19,116] E) Maintenance of brain temperature [85]. F) Transmission of signaling molecules from the periphery [65,66]. G) Regularization of non-Newtonian flow [121,122]. H) Providing oxygen for neuromodulator synthesis [54]. I) Mechanical signals for stabilization of vascular topology [131].