Hemodynamic low-frequency oscillation reflects resting-state neuronal activity in rodent brain

Brain functional connectivity is mapped using spontaneous low-frequency oscillations (LFOs) in blood-oxygen-leveldependent (BOLD) signals using fMRI. However, the origin of spontaneous BOLD oscillations remains elusive. Specifically, the coupling of regional hemodynamic LFOs to neuronal activity in a resting brain is rarely examined directly. Here we present a method based on instantaneous-frequency (IF) analysis to detect regional LFOs of cerebral blood flow (CBF) along with local-field potential (LFP) changes of neurons in resting state to study neurovascular coupling. CBF and LFP were simultaneously acquired using laser Doppler flowmetry (LDF) and electroencephalography in the rat's somatosensory cortex with high temporal resolution (i.e., 20Hz for CBF and 2kHz for LDF, respectively). Instead of fast Fourier transform analysis, a peak-detection algorithm was used to define the LFP activities and CBF spontaneous oscillations in the time domain and the time lapses were used to calculate the IFs of hemodynamic (i.e., CBF) oscillations and neuronal (i.e., LFP) activities. Our results showed that the CBF mostly oscillated at ∼0.1Hz with a full-half-bandwidth of [0.08Hz, 0.15Hz]. In addition, the maximal frequency of LFP firings was also approximately at 0.1Hz, which collaborated with to the frequency of CBF oscillations. Interestingly, CBF increased linearly with the LFP activity up to 0.15Hz (r=0.93), and both signals then decreased rapidly as a function of activity frequency. This indicates the spontaneous hemodynamic LFOs were associated with neuronal activities, thus confirming the neuronal origin of the hemodynamic oscillations.