Impact Factor for human Brain Mapping

System in the human brain

With the global demographic shift towards an older population, and the impact that age can have on cognition and dementia, there is a pressing need to understand the neurobiology of cognitive ageing. Functional brain imaging with functional magnetic resonance imaging (fMRI) has many advantages as a tool to study ageing and much of the current theoretical understanding of neurocognitive ageing has drawn on blood-oxygenation level-dependent (BOLD) based fMRI, linked to the cognitive ontologies from cognitive neuroscience. However, the BOLD signal is not a direct measure of neural activity, but is a complex convolution of neural and vascular signals (Logothetis, ). There is a risk therefore that fMRI studies that have been interpreted in terms of neural or neurocognitive change with age, instead reflect the effects of ageing on vasculature and neurovascular coupling.

Ageing affects the neural and vascular components of the BOLD fMRI signal differentially (D'Esposito et al., ; Hutchison et al., ). Without correction for vascular effects, the attribution of age-related differences in task-related BOLD signal to neural functioning may be overestimated (Liu et al., ). Several methods enable the estimation of vascular differences, including hypercapnia (Bright et al., ; Liu et al., ; Lu et al., ; Yezhuvath et al., ), breath-holding induced hypercapnia (Handwerker et al., ; Mayhew et al., ; Riecker et al., ; Thomason et al., ), cerebral blood flow and venous oxygenation (Liau and Liu, ; Lu et al., ; Restom et al., ). However, these are impractical in larger cohort studies of ageing, and may be poorly tolerated by older adults (for a review, see Liu et al., ). Additionally, hypercapnic challenge may not be entirely neuronally neutral: for example, participant awareness of the challenge might produce confounding effects in this normalization approach (Hall et al., ), suggesting a potential advantage for scaling approaches that offer “task-free” estimates of vascular reactivity.

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