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  • Review Article
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Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging

Key Points

  • Spontaneous blood oxygen level dependent (BOLD) fluctuations are not random noise, but are specifically correlated between functionally related brain regions and relate well to known anatomical systems.

  • Spontaneous BOLD fluctuations due to non-neuronal factors such as cardiac or respiratory activity can be isolated and are not responsible for the observed correlation patterns.

  • Spontaneous BOLD fluctuations are correlated with fluctuations in the power of high-frequency neuronal activity.

  • Spontaneous BOLD correlation patterns are largely consistent across different resting states, including sleep and anaesthesia, suggesting that they are an intrinsic property of the brain as opposed to being activity evoked by unconstrained mental activity.

  • Inter-subject variability in these correlation patterns relates to inter-subject variability in activation patterns and task performance.

  • Spontaneous BOLD fluctuations do not disappear during task paradigms but continue throughout, contributing to inter-trial variability in measured BOLD responses and behaviour.

Abstract

The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.

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Figure 1: Traditional fMRI analysis and BOLD noise.
Figure 2: Generation of resting-state correlation maps.
Figure 3: Intrinsically defined anticorrelated networks in the human brain.
Figure 4: Coherent spontaneous fluctuations account for variability in event-related BOLD responses.
Figure 5: Spontaneous BOLD activity in the anaesthetized macaque monkey.

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Acknowledgements

We thank Avi Snyder and Justin Vincent for their insights and valuable suggestions on this manuscript. This work was supported by grants NS06833 and F30 NS054398-01.

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FURTHER INFORMATION

Brain Spontaneous Correlation Analysis Processing Engine (BrainSCAPE)

Glossary

Blood oxygen level dependent signal

(BOLD). Signal used by fMRI as a non-invasive but indirect measure of changes in neuronal activity.

Noise

Modulation in a measured signal that is unrelated to the effect of interest. Noise is usually minimized through averaging, allowing the effect of interest to be emphasized.

Water phantom

Glass sphere containing water that is used to study fMRI signal properties in a non-biological system.

Linear regression

Computation of a scaling factor such that multiplication of a regressor time course by this scaling factor will remove the greatest amount of variance when subtracted from a signal of interest.

Voxel

A volume element that is the smallest distinguishable, box-shaped part of a three-dimensional space.

Power spectral density function

The distribution of power at each frequency in a time-varying signal, generally displayed with power on the y-axis and frequency along the x-axis.

Electroencephalography

(EEG). A technique used to measure neural activity by monitoring electrical signals from the brain that reach the scalp. EEG has good temporal resolution but relatively poor spatial resolution.

Magnetoencephalography

(MEG). A non-invasive technique that allows the detection of the changing magnetic fields that are associated with brain activity on a timescale of milliseconds.

Local field potential

Electrical fields recorded from microelectrodes in the brain that are thought to reflect the weighted average of input signals on the dendrites and cell bodies of neurons in the vicinity of the electrode.

Hypercapnia

Situation occurring when the amount of dissolved carbon dioxide in blood rises above its physiological mean of about 40 Torr.

Callosal agenesis

A rare birth defect in which the corpus callosum fails to develop.

Diffusion tensor imaging

(DTI). An MRI imaging technique that takes advantage of the restricted diffusion of water through myelinated nerve fibres in the brain to map the anatomical connectivity between brain areas.

Mentation

Mental activities of which a subject is consciously aware.

Mental imagery

The conscious recollection of an object or a scene in its absence.

Near-infrared spectroscopy

A form of optical imaging in which arrays of lasers and detectors are used to measure changes in the absorption of near-infrared light caused by neural activation.

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Fox, M., Raichle, M. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8, 700–711 (2007). https://doi.org/10.1038/nrn2201

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