Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound

Abstract

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 (VEPs) 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 a spatial-peak pulse-average acoustic intensity of 3 W/cm; 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 in 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 can also enhance the excitability depending on the acoustic intensity and the 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.

Figure 1

Illustration of the experimental procedures. (A) An overview of the experimental setup (B) An example of the averaged visual evoked potentials (VEP) (n = 100) measured from an individual rat. Square box shows the timing of the visual stimulation. The first positive and negative peaks of the VEP are indicated as 'P1' and 'N1', respectively. (C) Timeline of the experiment. Boxes indicate VEP sessions with or without FUS sonication: B = Baseline before sonication ('PreFUS'), S = FUS sonication or Control (CTL) without FUS, R = Resting after stimulation ('PostFUS').

Figure 2

The percentage changes in the VEP magnitude (P1 - N1, shown with standard error) in different data acquisition blocks (shown in horizontal axis) for (A) acoustic intensities of 1, 3, and 5 W/cm² at a fixed duty cycle of 5%, and (B) duty cycles of 1, 5, and 8.3% at a fixed acoustic intensity of 3 W/cm². For both (A) and (B), the unsonicated condition was included as a control group. Asterisk (*) indicates the significant group-level difference (P < 0.05), while dagger (†) indicates the marginal significance (P = 0.11), according to one-way ANOVA followed by post-hoc Tukey's test.