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The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation

Yi Yuan, Xingran Wang, Jiaqing Yan, Xiaoli Li

BMC Neuroscience 2018 · 10.1186/s12868-018-0476-2

rodenthealthyemg mep

Abstract

Background Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a noninvasive method with high spatial resolution and deep penetration. Previous studies have qualitatively demonstrated that the electromyographic response caused by LIPUS in the mouse motor cortex is affected by the anesthetic state of the mice. However, the quantitative relationship between motor response and anesthetic dose remains unclear. Results Experimental results show that the success rate decreases stepwise as the isoflurane concentration/mouse weight ratio increases (ratios: [0.004%/g, 0.01%/g], success rate: ~ 90%; [0.012%/g, 0.014%/g], ~ 40%; [0.016%/g, 0.018%/g], ~ 7%; 0.024%/g, 0). The latency and duration of EMG increase significantly when the ratio is more than 0.016%/g. Compared with that at ratios from 0.004 to 0.016%/g, normalized EMG amplitude decreases significantly at ratios of 0.018%/g and 0.020%/g. Conclusions Quantitative calculations indicate that the anesthetic dose has a significant regulatory effect on the motor response of mice during LIPUS. Our results have guiding significance for the selection of the anesthetic dose for LIPUS in mouse motor cortex experiments.

Abstract via europepmc.

Speciesmouse (BALB/c)
Subjects11 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsemg mepTail EMG: motor-response success rate, latency, duration, and normalized amplitude
Direction of effectexcitatoryLIPUS reliably evoked tail muscle EMG (motor) responses; response success rate and EMG amplitude decreased and latency/duration increased stepwise as the isoflurane concentration/body-weight ratio increased, with no responses at the highest dose tested (0.024%/g).
Adverse eventsnot reportedBioheat modelling using the study's maximum ultrasonic intensity (2 W/cm2) and pulse duration (0.2 s) estimated a maximum temperature rise of ~3.67x10^-3 degrees C, judged far below the threshold for thermal bioeffects.

Exposures

Exposure 1: LIPUS to mouse motor cortex across 11 isoflurane doses

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

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.3✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 30%
Sonication duration (s)0.2✓✓
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)2✓✓
Protocol, in the paper’s words

The PRF, SD (stimulation duration) and TBD (tone-burst duration) of the ultrasound were 1 kHz, 200 ms and 0.3 ms, respectively. Mice were anesthetized with one isoflurane concentration for 10 min before LIPUS, then LIPUS was performed for 5 min while tail EMG was recorded, followed by 5 more minutes of anesthesia; each mouse was then tested with the next of 11 isoflurane doses (0.1% to 0.6% in 0.05% steps, corresponding to ratios of 0.004%/g to 0.024%/g of body weight).

Flags from extraction

  • exposures[0].timing.sonication_duration_sPaper labels this value 'SD' (stimulation duration) rather than a named sonication/train duration; a later thermal-safety calculation independently uses 'pulse duration t=0.2 s', consistent with this value being the length of one uninterrupted train.
  • exposures[0].timing.duty_cycle_pctNot stated by the paper; arithmetic from TBD (0.3 ms) and PRF (1 kHz) would imply ~30%, but this was not computed here per instructions.
  • exposures[0].unspecified_domainPaper does not state whether the reported Isppa (~2 W/cm2) is a free-field or in-situ value; placed in unspecified_domain.
  • n_sessions_per_subjectEach of the 11 mice appears to have been tested at all 11 isoflurane doses (matching N=11 at every ratio), but the paper does not explicitly state the number of sessions per subject or whether doses were tested on separate days.