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Localization of Ultrasound-Induced In Vivo Neurostimulation in the Mouse Model

Randy L. King, Julian R. Brown, Kim Butts Pauly

Ultrasound in Medicine & Biology 2014 · 10.1016/j.ultrasmedbio.2014.01.020

rodenthealthyemg mep

Abstract

Developments in the use of ultrasound to stimulate and modulate neural activity have raised the possibility of using ultrasound as a new investigative and therapeutic tool in brain research. Although the phenomenon of ultrasound-induced neurostimulation has a long history dating back many decades, until now there has been little evidence of a clearly localized effect in the brain, a necessary requirement for the technique to become genuinely useful. Here we report clearly distinguishable effects in sonicating rostral and caudal regions of the mouse motor cortex. Motor responses measured by normalized electromyography in the neck and tail regions changed significantly when sonicating the two different areas of motor cortex. Response latencies varied significantly according to sonication location, suggesting that different neural circuits are activated depending on the precise focus of the ultrasound beam. Taken together, our findings present good evidence of the ability to target selective parts of the motor cortex with ultrasound neurostimulation in the mouse, an advance that should help to set the stage for developing new applications in larger animal models, including humans.

Abstract via europepmc.

Speciesmouse (CBL-7)
Subjects16 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsemg mep — EMG of neck, tail and forelimb (triceps) muscles; latency, success rate, normalized peak EMG amplitude
Direction of effectexcitatorySonication of motor cortex evoked neck and tail muscle contractions (success about 81-82 %); caudal sonication gave larger tail EMG and shorter latency, rostral gave larger neck EMG; no lateralisation between left and right.
Adverse eventsnone observedNo evidence of any noxious effect of the stimulation at the intensities used; animals appeared normal after recovery.

Exposures

Exposure 1: Rostral and caudal mouse motor cortex, 80 ms CW at 500 kHz

Target: motor cortex — “rostral and caudal regions of the mouse motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓

Pulse timing
Waveformcontinuous
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not applicable
Pulse repetition frequency (Hz)not applicable
Duty cycle (%)not applicable
Sonication duration (s)0.08✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)200✓✓✓⚑
Free-field Isppa (W/cm²)3✓✓✓⚑
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
Protocol, in the paper’s words

All experiments were conducted using 80-ms continuous wave ultrasound sonications. Sonications were delivered in pseudo-random sequence with a minimum interval of 5 s, only during quiescence in muscle activity; sham sonications at 0 W/cm2 were interleaved in 4 of 10 mice.

Consistency checks: intensity pressure inconsistent free field.

Flags from extraction

  • exposures[0].free_field.isppa_w_cm2 — Paper says only 'intensity of 3 W/cm2' and does not name the metric; placed under isppa by assumption. Calculated from hydrophone scans in a scanning tank, skull ignored, so recorded as free field.
  • species — Paper writes 'CBL-7 mice'; probably C57BL/6 but recorded as written.
  • exposures[0].free_field.pressure_kpa — 0.2 MPa stated in parentheses beside the intensity; converted to 200 kPa.
  • sham_type — Sham was 0 W/cm2 sonications; mechanism not described beyond zero intensity.
  • exposures[0].timing.protocol_description — Intensity varied 0.7 to 3 W/cm2 only during site-finding; main experiment at 3 W/cm2.