Neuromodulation Effect of Very Low Intensity Transcranial Ultrasound Stimulation on Multiple Nuclei in Rat Brain
Yingjian Liu, Gang Wang, Chao Cao, Gaorui Zhang, Emily B. Tanzi, Yang Zhang, Weidong Zhou, Yi Li
Frontiers in Aging Neuroscience 2021 · 10.3389/fnagi.2021.656430
Abstract
Objective Low-intensity transcranial ultrasound stimulation (TUS) is a non-invasive neuromodulation technique with high spatial resolution and feasible penetration depth. To date, the mechanisms of TUS modulated neural oscillations are not fully understood. This study designed a very low acoustic intensity (AI) TUS system that produces considerably reduced AI Ultrasound pulses ( I SPTA Methods We recorded the local field potential (LFP) of five brain nuclei under TUS with three groups of simulating parameters. Spectrum estimation, time-frequency analysis (TFA), and relative power analysis methods have been applied to investigate neural oscillation patterns under different stimulation parameters. Results Under PRF, 500 Hz and 1 kHz TUS, high-amplitude LFP activity with the auto-rhythmic pattern appeared in selected nuclei when I SPTA exceeded 12 mW/cm 2 . With TFA, high-frequency energy (slow gamma and high gamma) was significantly increased during the auto-rhythmic patterns. We observed an initial plateau in nuclei response when I SPTA reached 16.4 mW/cm 2 for RPF 500 Hz and 20.8 mW/cm 2 for RPF 1 kHz. The number of responding nuclei started decreasing while I SPTA continued increasing. Under 1.5 kHz TUS, no auto-rhythmic patterns have been observed, but slow frequency power was increased during TUS. TUS inhibited most of the frequency band and generated obvious slow waves (theta and delta band) when stimulated at RPF = 1.5 kHz, I SPTA = 8.8 mW/cm 2 . Conclusion These results demonstrate that very low intensity Transcranial Ultrasound Stimulation (VLTUS) exerts significant neuromodulator effects under specific parameters in rat models and may be a valid tool to study neuronal physiology.
Abstract via europepmc.
Exposures
Exposure 1: VLTUS, three PRF groups
Target: primary somatosensory cortex, primary motor cortex, habenula, CA1, hippocampus — “five nuclei: SI, CA1, CA2, LHb, and MI”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.4, 0.2, 0.134swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 500, 1,000, 1,500swept | ✓✓✓ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | not reported | ⚑ |
| 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) | 0.036, 0.044, 0.06, 0.082swept | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.0072, 0.0256swept | ✓✓✓ |
Fixed 500 kHz and 20% duty cycle; three trial groups with PRF 500 Hz (200 cycles per pulse), 1 kHz (100 cycles per pulse) and 1.5 kHz (67 cycles per pulse), with amplifier gain increased across trials to raise intensity. Stimulation duration is not stated; LFP power was compared over 10 s before and after stimulation.
Flags from extraction
exposures[0].unspecified_domain.isppa_w_cm2— Table 1 lists ISPPA only up to 0.082 W/cm2 (ISPTA 16.4 mW/cm2) while the text reports ISPTA up to 25.6 mW/cm2; the upper ISPPA limit is therefore probably understated. The paper does not say whether the values are before or after the 83.9% skull attenuation.exposures[0].timing.pulse_duration_ms— Pulse duration not stated in ms; only cycles per pulse (200, 100, 67) are given in Table 1.exposures[0].timing.sonication_duration_s— Stimulation duration (SD) appears in a figure schematic but its value is not stated in the text.exposures[0].target.terms— Stimulation was applied from the occipital side (6.5 mm lateral of midline, 4 mm posterior of bregma) with a collimator and a plane transducer; LFP was recorded in S1, M1, LHb, CA1 and CA2. The recorded nuclei are listed as the target; CA2 mapped to hippocampus.n_subjects— Two rats, each repeated three times per parameter set.exposures[0].device.family— No transducer maker or model is named.