MAPPING THE SONICATION PARAMETER SPACE TO CHARACTERISE NEUROMODULATION BY ULTRASOUND STIMULATION IN THE HIPPOCAMPUS

Transcranial focused ultrasound stimulation (tFUS) is a promising tool for non-invasive neuromodulation. However, how acoustic parameters interact to direct the effects of tFUS on neural circuit function remains poorly understood. We investigated how variations in duty cycle (DC) and spatial peak pulse average intensity (ISPPA) affect network function in acute hippocampal slices prepared from Han Wistar rats (n=20) following ultrasound stimulation. A) 5Hz pulse repetition frequency (PRF) and sonication duration of 40 seconds were constant across all conditions, based on previous work demonstrating a reliable increase in offline circuit function. By fixing PRF and duration, we aimed to isolate the specific contributions of DC and ISPPA to post-sonication neuromodulation. We tested nine ultrasound conditions combining three DCs (10, 30, and 50%) and three intensities (0.5, 1, and 2 W/cm²), selected to remain within established safety thresholds whilst providing a range of profiles. A sham condition was included to control for non-acoustic effects. We assessed changes in neuronal function using extracellular field recordings measuring fEPSPs and FVs recorded from the CA1 stratum radiatum with increasing stimulation strength of the Schaffer collaterals (0-20V in 1V increments). Results indicate that both DC and ISPPA influence network function post-sonication, but not in a linear manner. Changing parameters provides a unique mechanical profile of the sound waves, meaning the mechanical force and action may differ, which could reflect preferential activation of different mechanosensitive ion channels. Identifying the relationship between DC and ISPPA under otherwise matched conditions informs the selection of ultrasound paradigms for future applications.