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Disease and the brain's dark energy

Abstract

Brain function has traditionally been studied in terms of physiological responses to environmental demands. This approach, however, ignores the fact that much of the brain's energy is devoted to intrinsic neuronal signaling. Recent studies indicate that intrinsic neuronal activity manifests as spontaneous fluctuations in the blood oxygen level-dependent (BOLD) functional MRI (fMRI) signal. The study of such fluctuations could potentially provide insight into the brain's functional organization. In this article, we begin by presenting an overview of the strategies used to explore intrinsic neuronal activity. Considering the possibility that intrinsic signaling accounts for a large proportion of brain activity, we then examine whether the functional architecture of intrinsic activity is altered in neurological and psychiatric diseases. We also review a clinical application of brain mapping, in which intrinsic activity is employed for the preoperative localization of functional brain networks in patients undergoing neurosurgery. To end the article, we explore some of the basic science pursuits that have been undertaken to further understand the physiology behind intrinsic activity as imaged with BOLD fMRI.

Key Points

  • The majority of the brain's energy is devoted to intrinsic neuronal signaling

  • Intrinsic neuronal activity manifests as spontaneous fluctuations in the blood oxygen level-dependent functional MRI (fMRI) signal and exhibits synchrony within neuroanatomically and functionally related brain regions

  • Many established methods, each with its own advantages and disadvantages, are available for characterizing synchrony in intrinsic neuronal activity (functional connectivity)

  • Changes in functional connectivity have been reported in various neurological and psychiatric diseases, and such alterations might have potential as clinical biomarkers in the long term

  • Functional connectivity has potential as a preoperative functional brain mapping tool to indicate the regions that should be avoided during surgery

  • Much of the progress that has been made in our basic science understanding of intrinsic neuronal activity, as detected by fMRI, will aid the interpretation of clinical changes during disease

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Figure 1: Intrinsic neuronal activity is synchronous within neuroanatomically and functionally related regions of the brain.
Figure 2: Functional connectivity on different spatial scales visualized using various complementary techniques.
Figure 3: Functional connectivity and brain lesions.

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Acknowledgements

We would like to thank Abraham Z. Snyder and Benjamin J. Shannon (Mallinckrodt Institute of Radiology, Washington University, St Louis, MO, USA) for their insightful comments and valuable suggestions throughout the writing process. Funding for this work was provided by NIH grant NS06833 and National Institute of Mental Health grant F30 MH083483.

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Correspondence to Marcus E. Raichle.

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Supplementary information

Supplementary References (DOC 80 kb)

Supplementary Figure Legend 1

Intrinsic neuronal activity is synchronous within neuroanatomically and functionally related regions of the brain. (DOC 28 kb)

Supplementary Figure Legend 2

Functional connectivity on different spatial scales can be visualized using various complementary techniques. (DOC 1200 kb)

Supplementary Figure Legend 3

Functional connectivity and brain lesions. (DOC 24 kb)

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Zhang, D., Raichle, M. Disease and the brain's dark energy. Nat Rev Neurol 6, 15–28 (2010). https://doi.org/10.1038/nrneurol.2009.198

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