Abstract
Transcranial ultrasound stimulation (tUS) is a promising non-invasive approach to modulate brain circuits. The application is gaining popularity, however the full effect of ultrasound stimulation is still unclear and further investigation is needed. This study aims to apply optical intrinsic signal imaging (OISI) for the first time, to simultaneously monitor the wide-field cerebral hemodynamic change during tUS on awake animal with high spatial and temporal resolution. Three stimulation paradigms were delivered using a single-element focused transducer operating at 425 kHz in pulsed mode having the same intensity (ISPPA = 1.84 W/cm2, ISPTA = 129 mW/cm2) but varying pulse repetition frequencies (PRF). The results indicate a concurrent hemodynamic change occurring with all actual tUS but not under a sham stimulation. The stimulation initiated the increase of oxygenated hemoglobin (HbO) and decrease of deoxygenated hemoglobin (RHb). A statistically significant difference (p < 0.05) was found in the amplitude change of hemodynamics evoked by varying PRF. Moreover, the acoustic stimulation was able to trigger a global as well as local cerebral hemodynamic alteration in the mouse cortex. Thus, the implementation of OISI offers the possibility of directly investigating brain response in an awake animal during tUS through cerebral hemodynamic change.
Highlights
Brain stimulation plays an important role in both general neuroscience as well as in clinical applications[1,2,3]
The spatial map demonstrated that hemodynamic activity was distributed over the entire mouse cortex, while the time series showed the hemodynamic changes to be initiated shortly after the start of stimulation, reaching the maximum peak after 2.76 ± 0.51 s, with no changes observed during the sham stimulation
To confirm that the observed optical changes are due to cerebral hemodynamics rather than the ultrasound wave affecting the optical characteristics of the medium[43,44], we performed additional experiment on two other mice
Summary
Brain stimulation plays an important role in both general neuroscience as well as in clinical applications[1,2,3]. Several studies have been conducted to measure the effect of tUS by simultaneous recording of electrical activity in the brain using electroencephalogram (EEG)[24,25], multi-unit activity (MUA)[26] and local field potential (LFP)[27], as well as in muscle using electromyography (EMG)[28] These approaches provide a direct measure of neural response to US with superior temporal resolution but are unable to offer a broader view of brain activity at high spatial resolution. The application of OISI in brain studies was driven by the similarity in contrast mechanism with fMRI which primarily uses the blood-oxygen level dependent (BOLD) signal as an indicator of neural activity through the hemodynamic response function (HRF). The OISI technique has been used in various neuroscience studies to investigate functional brain connectivity[38,39], anaesthetic effect on the brain[32], as well as to explore other neuromodulation approaches[40,41]
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