Hemodynamic signals are widely used to infer neural activity in the brain. We tested the hypothesis that hemodynamic signals faithfully report neural activity during voluntary behaviors by measuring cerebral blood volume (CBV) and neural activity in the somatosensory cortex and frontal cortex of head-fixed mice during locomotion. Locomotion induced a large and robust increase in firing rate and gamma-band (40-100 Hz) power in the local field potential in the limb representations in somatosensory cortex, and was accompanied by increases in CBV, demonstrating that hemodynamic signals are coupled with neural activity in this region. However, in the frontal cortex, CBV did not change during locomotion, but firing rate and gamma-band power both increased, indicating a decoupling of neural activity from the hemodynamic signal. These results show that hemodynamic signals are not faithful indicators of the mean neural activity in the frontal cortex during locomotion; thus, the results from fMRI and other hemodynamic imaging methodologies for studying neural processes must be interpreted with caution.
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