DISENTANGLING NEUROMODULATION AND ARTEFACTS INDUCED BY TRANSCRANIAL ULTRASOUND STIMULATION: LIMITED ELECTROPHYSIOLOGICAL EVIDENCE FOR NEUROMODULATION IN THE SOMATOSENSORY CORTEX OF ANESTHETIZED RATS

Low-intensity transcranial focused ultrasound stimulation (TUS) is an emerging, non-invasive neuromodulation method that offers high spatial precision and the ability to target deep brain regions. Therefore, interest in TUS has grown rapidly with many studies reporting promising effects. However, uncertainties remain regarding its underlying mechanism, effectiveness and reproducibility. To address these concerns, this study investigated the electrophysiological effects of TUS on the somatosensory cortex of anesthetized rats by examining somatosensory evoked potentials (SSEPs) and TUS-evoked neural activity.
Electrophysiological recordings were obtained using a 32-channel silicon probe during a 30-minute alternating paradigm, in which every other forepaw-evoked SSEP was stimulated with TUS (500kHz, 1.5MPa), controlling for the natural SSEP variability over time. As TUS induced artefacts in these recordings that mimicked neuromodulation effects, rigorous controls and artefact removal were foreseen.
At the instantaneous level, TUS did not significantly alter SSEP amplitudes or peak-to-peak values, even when applied through a craniotomy. Similarly, no long-term changes in SSEP measures were observed compared to control conditions. Current source density analysis further revealed no significant TUS-induced modulation of synaptic currents across cortical layers.
Additionally, we assessed whether TUS could evoke activity rather than modulate ongoing responses. This analysis revealed a TUS-evoked potential (EP) with peak at 6ms. Similar EPs were observed with visual cortex, earbar or sound stimulation but not during tail stimulation, suggesting a non-specific vibrational origin.
In conclusion, under the conditions tested, TUS did not produce clear neuromodulatory effects in the somatosensory cortex but could induce an EP although the origin remained unclear.