Parameter-dependent offline modulation of motor cortical excitability by transcranial low-intensity focused ultrasound: Evidence from rat models
Shu-Mei Yang, Jia-Rong Wu, Yu-Ling Lin, Sung-Jan Lin, Wen-Shiang Chen, Ming-Yen Hsiao
Brain Research 2025 · 10.1016/j.brainres.2025.149813
Abstract
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/cm 2 , 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/cm 2 , 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.
Abstract via europepmc.
Exposures
Exposure 1: LIFU 500 kHz, high-duty-cycle pulsed and low-duty-cycle burst-mode, 0.11 and 0.21 W/cm2 Ispta
Target: primary motor cortex — “primary motor cortex responsible for the forelimb”
Device: Sonic Concepts · Sonic Concepts · H 104 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 250 | ✓✓✓ |
| Duty cycle (%) | 50, 7.5sweptpulse duration × PRF gives 50% | ✓✓✓⚑ |
| Sonication duration (s) | 600 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 0.23, 0.42, 1.51, 2.82swept | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.11, 0.21swept | ✓✓✓ |
Two modes for 10 min each: continuous pulsing at PRF 250 Hz, 2 ms pulses, 50 % DC; or burst mode with 300-ms pulse trains every 2 s (PRF 250 Hz, 2 ms pulses, 50 % intra-train DC, total DC 7.5 %). MEPs measured about 5 min before and after.
Flags from extraction
n_subjects— 50 rats in five groups of 10; the 10 controls received no ultrasound, so 40 were sonicated.exposures[0].unspecified_domain.isppa_w_cm2— Isppa values are read from Table 1 rows 2 to 5 (0.23, 0.42, 1.51, 2.82); domain not stated.exposures[0].timing.sonication_duration_s— Total session is 10 min; in burst mode the train is 300 ms every 2 s. Recorded the session length.exposures[0].timing.duty_cycle_pct— Burst-mode total DC 7.5 % arises from 300 ms train every 2 s at 50 % intra-train DC; both values stated in text.