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

Nature Reviews Neuroscience volume 4, pages 863–872 (2003)Cite this article

Key Points

  • Neural activity influences the haemodynamic properties of the cerebral vasculature in a number of ways. The increase in local blood flow and subsequent decrease in the local concentration of deoxygenated haemoglobin that occur at the site of neural activity are the basis of the blood-oxygen-level-dependent (BOLD) signal that is measured by functional magnetic resonance imaging (fMRI). Changes in neurovascular coupling that occur with age or disease might alter the BOLD signal.

  • Vasodilators that are probably mediators of neurovascular coupling include: K+, which is released from active nerve terminals; nitric oxide (NO), which is probably produced by neuronal NO synthase; release of eicosanoids by astrocytes, stimulated by glutamate; and possibly other neurotransmitters.

  • Changes in cerebrovascular ultrastructure during ageing result largely from arteriosclerotic changes, which probably decrease the elasticity and compliance of affected vessels. If cerebral vessels are occluded, post-stenotic compensatory dilation might reduce the dynamic range of vascular reactivity in the affected area.

  • Ageing is also associated with a decrease in resting cerebral blood flow, cerebral metabolic rate of O2 consumption and vascular reactivity. There is evidence that the BOLD signal shows a decreased signal-to-noise ratio in older subjects, probably because of a greater level of noise. In individuals with cerebrovascular disease, neurovascular coupling has also been found to be altered, although only two studies have been reported.

  • These findings have implications for fMRI studies that aim to compare neural activity between ageing or diseased populations and young or healthy subjects. It might be necessary to screen subjects carefully for cerebrovascular abnormalities. Possible alterations in neurovascular coupling must be considered when interpreting the results of such studies.

  • Advances in the design or analysis of experiments should make it easier to distinguish between changes in neurovascular coupling and changes in neural activity. The combination of functional imaging with other techniques, such as the measurement of event-related potentials, might also be helpful in this regard.

Abstract

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.

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Figure 1: Schematic of the transformation of neural activity elicited by a stimulus to a haemodynamic response resulting in a blood-oxygen-level-dependent (BOLD) signal.
Figure 2: Some of the suspected mediators of neurovascular coupling.
Figure 3: Ultrastructural changes observed in the cerebral microvasculature of elderly individuals as compared with younger individuals.
Figure 4: Empirical observations of decreased signal-to-noise ratio in the blood-oxygen-level-dependent (BOLD) signal of older individuals as compared with younger individuals.
Figure 5: Abnormal blood-oxygen-level-dependent (BOLD) signal in patients with cerebrovascular pathology.

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Article 13 May 2021

David S. Knopman, Helene Amieva, … David T. Jones

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Acknowledgements

This work was supported by the National Institutes of Health and the American Federation for Aging Research.

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Authors and Affiliations

  1. Helen Wills Neuroscience Institute and Department of Psychology, Henry H. Wheeler Jr. Brain Imaging Center, University of California, Berkeley, 3210 Tolman Hall, Berkeley, 94720-1650, California, USA

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

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  1. Mark D'Esposito
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  2. Leon Y. Deouell
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  3. Adam Gazzaley
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Correspondence to Mark D'Esposito.

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FURTHER INFORMATION

Encyclopedia of Life Sciences

ageing and the brain

brain imaging as a diagnostic tool

Glossary

RESISTANCE VESSELS

Arterioles and small arteries.

ISCHAEMIA

A condition of insufficient oxygen delivery to a tissue.

CAROTID STENOSIS

The condition in which one or both carotid arteries (the arteries in the neck that supply blood to the brain) is narrowed or blocked. Can lead to stroke secondary to decreased blood flow in the brain region that it supplies.

ATHEROSCLEROSIS

A condition in which fatty material is deposited along the walls of arteries, which then thickens, hardens, and might eventually block the arteries.

TRANSCRANIAL DOPPLER ULTRASOUND

A non-invasive method that is used to assess blood-flow velocity in intracranial vessels and then make determinations about intracranial haemodynamics, such as cerebral blood flow (CBF).

CEREBRAL AUTOREGULATION

The intrinsic ability of cerebral vessels to maintain a relatively constant, steady-state CBF despite large changes in arterial blood pressure.

T2-WEIGHTED

A magnetic resonance imaging (MRI) recording sequence that provides sensitivity to pathologic processes through changes in water content. T2 is often lengthened for oedema and demyelination.

FLAIR

FLAIR (fluid-attenuated inversion recovery) is a T2-weighted MRI image that has the advantage of separating white-matter lesions from cerebrospinal fluid-like lesions.

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D'Esposito, M., Deouell, L. & Gazzaley, A. Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci 4, 863–872 (2003). https://doi.org/10.1038/nrn1246

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