Neurovascular coupling and energy metabolism in the developing brain

Abstract

In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations.

Neurovascular coupling develops alongside neural circuits in the postnatal brain

“…In fact, this conclusion is highly consistent with the extensive neural and vascular development that is known to occur in the postnatal brain 14,20,23,25,41 as elaborated below:…”

Imaging structural and functional brain development in early childhood

“…Nevertheless, non-invasive brain imaging of awake infants remains challenging owing to their motion and their inability to perform certain tasks, which limit such studies to a restricted set of brain functions. Moreover, the neurovascular coupling mechanism is known to be immature during this stage 83 since key components enabling such coupling, including neurons, astrocytes, pericytes, and the brain’s vasculature, are still actively developing during infancy. The best approaches to model infant BOLD-based activation detection is still an active area of research 74 (Box 4).…”

Neurovascular coupling in the developing neonatal brain at rest

“…NVC has been well characterized in adults by an increase in blood flow in response to neuronal activation (Jobsis, ). The balance between local consumption and arterial blood supply related to neuronal activation is much more delicate in the developing brain (Kozberg & Hillman, ). The way in which this NVC is affected by particular metabolic and vascular disorders (Attwell & Iadecola, ; Sheth et al, ), in the immature brain is clinically relevant with respect to the neurodevelopmental consequences of NVC dysfunction.…”

“…In contrast, in preterm neonates, we observed NVC from 28 weeks GA in response to either spontaneous endogenous bursts of activity (Roche‐Labarbe et al, ) or exogenous phonemes or voice stimulation (Mahmoudzadeh et al, ). Although the response of the vascular network in adults has been clearly shown to consist of positive NVC (increase in oxy‐hemoglobin [HbO], total hemoglobin [HbT], and blood volume and a decrease in deoxy‐hemoglobin [HbR]), increases and decreases of blood flow or blood volume have been reported in response to exogenous stimulation in neonates or preterm infants, see for example (A. P. Born et al, ; P. Born et al, ; G. Erberich, Friedlich, & Seri, ; S. G. Erberich et al, ; Heep et al, ; Kozberg et al, ; Mahmoudzadeh, Dehaene‐Lambertz, & Wallois, ), and in immature animals (Colonnese, Phillips, Constantine‐Paton, Kaila, & Jasanoff, ), suggesting interstudy, intersubject, and even intrasubject regional variability in early development (Kozberg & Hillman, ). It has also been shown that sleep influences cerebral blood flow index in neonates.…”