Reversible neuroinhibition by focused ultrasound is mediated by a thermal mechanism

Background: Transcranial focused ultrasound (tFUS) at low intensities has been reported to directly evoke responses and reversibly inhibit function in the central nervous system. While some doubt has been cast on the ability of ultrasound to directly evoke neuronal responses, spatially-restricted transcranial ultrasound has demonstrated consistent, inhibitory effects, but the underlying mechanism of reversible suppression in the central nervous system is not well understood. Objective/hypothesis: In this study, we sought to characterize the effect of transcranial, low-intensity, focused ultrasound on the thalamus during somatosensory evoked potentials (SSEP) and investigate the mechanism by modulating the parameters of ultrasound. Methods: TFUS was applied to the ventral posterolateral nucleus of the thalamus of a rodent while electrically stimulating the tibial nerve to induce an SSEP. Thermal changes were also induced through an optical fiber that was image-guided to the same target. Results: Focused ultrasound reversibly suppressed SSEPs in a spatially and intensity-dependent manner while remaining independent of duty cycle, peak pressure, or modulation frequency. Suppression was highly correlated and temporally consistent with in vivo temperature changes while producing no pathological changes on histology. Furthermore, stereotactically-guided delivery of thermal energy through an optical fiber produced similar thermal effects and suppression. Conclusion: We confirm that tFUS predominantly causes neuroinhibition and conclude that the most primary biophysical mechanism is the thermal effect of focused ultrasound.