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Nature Reviews Neuroscience 4, 863–872 (1 November 2003) | doi:10.1038/nrn1246

Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging

Mark D'Esposito , Leon Y. Deouell & Adam Gazzaley

Functional magnetic resonance imaging (fMRI) has rapidly emerged as a powerful tool for studying brain function, despite the fact that it measures neuronal activity indirectly, through the blood-oxygen-level-dependent (BOLD) signal. The BOLD signal depends on neurovascular coupling — the processes by which neural activity influences the haemodynamic properties of the surrounding vasculature. Although the exact mechanisms that underlie neurovascular coupling are not completely understood, there is empirical evidence that these mechanisms might be altered in normal ageing and disease. So, interpretation of BOLD fMRI studies of individuals with different ages or pathology might be more challenging than is commonly acknowledged.