Time-frequency cross-coupling between cortical low-frequency neuronal calcium oscillations and blood oxygen metabolism evoked by ultrasound stimulation.

Low-intensity transcranial ultrasound stimulation (TUS) can modulate the coupling of high-frequency (160-200 Hz) neural oscillations and cerebral blood oxygen metabolism (BOM); however, the correlation of low-frequency (0-2 Hz) neural oscillations with BOM in temporal and frequency domains under TUS remains unclear. To address this, we monitored the TUS-evoked neuronal calcium oscillations and BOM simultaneously in the mouse visual cortex by using multimodal optical imaging with a high spatiotemporal resolution. We demonstrated that TUS can significantly increase the intensity of the neuronal calcium oscillations and BOM; the peak value, peak time, and duration of calcium oscillations are functionally related to stimulation duration; TUS does not significantly increase the neurovascular coupling strength between calcium oscillations and BOM in the temporal domain; the time differences of the energy peaks between TUS-induced calcium oscillations and BOM depend on their spectral ranges; the frequency differences of the energy peaks between TUS-induced calcium oscillations and BOM depend on their time ranges; and TUS can significantly change the phase of calcium oscillations and BOM from uniform distribution to a more concentrated region. In conclusion, ultrasound stimulation can evoke the time-frequency cross-coupling between the cortical low-frequency neuronal calcium oscillations and BOM in mouse.