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.
Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine’s effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.