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Neuromodulation Effects of Ultrasound Stimulation Under Different Parameters on Mouse Motor Cortex

Xingran Wang, Jiaqing Yan, Zhijie Wang, Xiaoli Li, Yi Yuan

IEEE Transactions on Biomedical Engineering 2020, 67, 291-297 · 10.1109/tbme.2019.2912840

rodenthealthyinvasive electrophysiologybehaviour

Abstract

Objective Although low-intensity transcranial ultrasound stimulation (TUS) enhances/suppresses neural oscillations and causes electroencephalography changes in the motor cortex, researchers have not clearly determined the manner in which the relative power and entropy of neural oscillations in the motor cortex vary with ultrasonic parameters, such as ultrasound intensity, stimulation duration (SD), and duty cycle. Methods In this paper, we use the transcranial ultrasound of different parameters to stimulate the mouse motor cortex, cause tail muscle contraction and movement, and simultaneously record local field potentials (LFPs) in the mouse motor cortex. The relative power and entropy of the LFPs under different ultrasonic parameters are analyzed. Results The relative power of the theta [4-8 Hz] frequency bands decreases with an increase in spatial-peak and pulse-average intensity (I sppa ) at 0-0.5 s and 0.5-1 s; the relative power of the gamma [30-45 Hz] frequency bands increases with an increase in I sppa at 0-0.5 s and 0.5-1 s; the relative power each of the gamma [30-45 Hz] and high gamma [55-100 Hz] frequency bands increases with an increase in the SD at 0-0.5 s and 0.5-1 s; the entropy values decrease with increases in I sppa and SD at 0-0.5 s. Conclusion The relative power and entropy of neural oscillations in the motor cortex can be modulated by TUS with different parameters, namely, ultrasound intensity and stimulation duration.

Abstract via europepmc.

Speciesmouse (BALB/c)
Subjects19 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, behaviourTail motor response (movement) monitored during TUS
Direction of effectmixed or unclearRelative power of theta band decreased while relative power of gamma and high-gamma bands increased with increasing Isppa and stimulation duration; LFP entropy decreased with increasing Isppa and SD; no significant effect of duty cycle was found.
Adverse eventsnot reportedThermal modelling estimated a maximum temperature increase of ~4.8x10^-3 degrees C at the highest intensity and longest duration used, considered far below the threshold for thermal bioeffects.

Exposures

Exposure 1: TUS of mouse motor cortex, sweep of intensity/duration/duty cycle

Target: motor cortex — “motor cortex
Device: Olympus / Panametrics · Olympus, USA · V301-SU

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)10, 20, 30, 40swept✓✓
Sonication duration (s)0.1, 0.2, 0.3, 0.4swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot 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)0.2, 0.4, 0.8, 1.1swept?
Protocol, in the paper’s words

The FF and PRF of the ultrasound were 500 and 1 kHz, respectively. Other combinations of the ultrasound parameters Isppa, SD, and DC are displayed in Table I. The other ultrasonic parameters remained unchanged so that we could quantitatively analyze the changes in parameters of LFP with a single ultrasonic parameter. TUS group (19 mice): The mice in the TUS group were used to analyze the effects of TUS of different parameters on neural oscillations.

Flags from extraction

  • n_subjects33 mice were used in total (19 TUS, 5 sham, 9 dead-animal control for electrode-vibration noise); n_subjects reports only the active TUS group since sham/control did not receive brain-penetrating stimulation intended to modulate neural activity.
  • exposures[0].sham_typeSham group received real ultrasound output but with the collimator oriented parallel to the skull so the wave would not penetrate into brain tissue; classified as inactive_transducer (aimed away) but mechanism differs from a powered-off transducer.
  • exposures[0].unspecified_domain.isppa_w_cm2Field distribution (kPa) was measured 'under the skull' by hydrophone (ex vivo skull), but the paper does not explicitly state whether the reported Isppa sweep values are free-field or in-situ/through-skull; domain left unspecified.