Separating vascular and neuronal effects of age on fMRI BOLD signals

TL;DR

This paper reviews methods to distinguish vascular and neuronal influences on fMRI BOLD signals in aging, emphasizing the importance of accounting for vascular effects to accurately interpret neurocognitive aging studies.

Contribution

It provides a comprehensive review of current techniques to separate vascular and neuronal components in fMRI data related to aging, highlighting their significance.

Findings

Vascular and neuronal factors influence BOLD signals differently with age.

Few studies have applied correction techniques for vascular effects in aging research.

Neurovascular interactions play a complex role in brain health and disease.

Abstract

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood-oxygen-level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. In contrast to over 10,000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease.