Background Transcranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation. Objective The objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague-Dawley rats. Methods We transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650 kHz of fundamental frequency. Results We observed that motor responses were elicited at minimum threshold acoustic intensities (4.9–5.6 W/cm2 in spatial-peak pulse-average intensity; 2.5–2.8 W/cm2 in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1–5 ms of tone-burst duration, 50% of duty cycle, and 300 ms of sonication duration, at 350 kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication. Conclusion Our results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.

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We investigated the use of pulsed low-intensity focused ultrasound (FUS) to suppress the visual neural response induced by light stimulation in rodents. FUS was administered transcranially to the rat visual cortex using different acoustic intensities and pulsing duty cycles. The visual evoked potentials (VEP) generated by an external strobe light stimulation were measured three times before, once during, and five times after the sonication. The VEP magnitude was suppressed during the sonication using a 5% duty cycle (pulse-repetition frequency of 100 Hz) and spatial-peak pulse-average acoustic intensity of 3 W/cm2; however, this suppressive effect was not present when a lower acoustic intensity and duty cycle were used. The application of a higher intensity and duty cycle resulted in a slight elevation of VEP magnitude, which suggested excitatory neuromodulation. Our findings demonstrate that the application of pulsed FUS to the region-specific brain area not only suppresses its excitability, but also can enhance the excitability depending on the acoustic intensity and rate of energy deposition. This bimodal feature of FUS-mediated neuromodulation, which has been predicted by numerical models on neural membrane capacitance change by the external acoustic pressure waves, suggests its versatility for neurotherapeutic applications.