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Cerebral Cortex Advance Access originally published online on December 5, 2007
Cerebral Cortex 2008 18(8):1814-1827; doi:10.1093/cercor/bhm208
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Negative BOLD with Large Increases in Neuronal Activity

Ulrich Schridde1, Manjula Khubchandani2, Joshua E. Motelow1, Basavaraju G. Sanganahalli2,3, Fahmeed Hyder2,3,4 and Hal Blumenfeld1,3,5,6

1 Department of Neurology, 2 Department of Diagnostic Radiology, 3 Quantitative Neuroscience with Magnetic Resonance and Magnetic Resonance Research Center, 4 Department of Biomedical Engineering, 5 Department of Neurobiology, 6 Department of Neurosurgery, Yale University, New Haven, CT 06510, USA

Address correspondence to Hal Blumenfeld, MD PhD, Department of Neurology, Yale University, 333 Cedar Street, New Haven, CT 06520-8018, USA. Email: hal.blumenfeld{at}yale.edu.

Blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used in neuroscience to study brain activity. However, BOLD fMRI does not measure neuronal activity directly but depends on cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO2 modeling, we investigated how the signals are related during seizures in rats. We found that increases in hemodynamic, neuronal, and metabolic activity were associated with positive BOLD signals in the cortex, but with negative BOLD signals in hippocampus. Our data show that negative BOLD signals do not necessarily imply decreased neuronal activity or CBF, but can result from increased neuronal activity, depending on the interplay between hemodynamics and metabolism. Caution should be used in interpreting fMRI signals because the relationship between neuronal activity and BOLD signals may depend on brain region and state and can be different during normal and pathological conditions.

Key Words: cerebral blood flow • epilepsy • fMRI • hippocampus • neuroimaging • neurovascular coupling


Ulrich Schridde and Manjula Khubchandani have contributed equally to the study.


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D. J. Englot, A. M. Mishra, P. K. Mansuripur, P. Herman, F. Hyder, and H. Blumenfeld
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[Abstract] [Full Text] [PDF]



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