Parameter-dependent offline modulation of motor cortical excitability by transcranial low-intensity focused ultrasound: Evidence from rat models.

Transcranial low-intensity focused ultrasound (LIFU) has emerged as a promising tool for non-invasive brain stimulation; however, evidence regarding its offline neuromodulatory effects and parameter-dependent modulation remains limited. This study investigated the effects of varying acoustic intensities and stimulation modes of LIFU on motor cortical excitability. LIFU was applied to the primary motor cortex using a fundamental frequency of 0.5 MHz, a pulse repetition frequency of 250 Hz, duty cycles of 7.5 % or 50 %, spatial peak temporal average intensities of 0.11 or 0.21 W/cm², and a duration of 10 min. Motor evoked potentials (MEPs) and motor thresholds (MTs) were assessed in rats using transcranial magnetic stimulation before and 5 min after LIFU. A significant increase in MEP amplitude (median 6.86 %, interquartile range -0.65-20.09 %, p = 0.037) was observed in the group exposed to a duty cycle of 7.5 % and an intensity of 0.11 W/cm², while no significant changes in MEP amplitude occurred in other experimental groups. MEP latency and MTs remained unchanged across all groups after LIFU application. These findings demonstrate that LIFU modulates motor cortical excitability in a parameter-dependent manner, with lower intensity burst-mode pulsed LIFU showing an excitatory effect, providing valuable insights for future neuromodulation research.