← Explore

High-Resolution Focused Ultrasound Neuromodulation Induces Limb-Specific Motor Responses in Mice in Vivo

Christian Aurup, Hermes A.S. Kamimura, Elisa E. Konofagou

Ultrasound in Medicine & Biology 2021, 47, 998-1013 · 10.1016/j.ultrasmedbio.2020.12.013

rodenthealthyemg mep

Abstract

Ultrasound can modulate activity in the central nervous system, including the induction of motor responses in rodents. Recent studies investigating ultrasound-induced motor movements have described mostly bilateral limb responses, but quantitative evaluations have failed to reveal lateralization or differences in response characteristics between separate limbs or how specific brain targets dictate distinct limb responses. This study uses high-resolution focused ultrasound (FUS) to elicit motor responses in anesthetized mice in vivo and four-limb electromyography (EMG) to evaluate the latency, duration and power of paired motor responses (n = 1768). The results indicate that FUS generates target-specific differences in electromyographic characteristics and that brain targets separated by as little as 1 mm can modulate the responses in individual limbs differentially. Exploiting these differences may provide a tool for quantifying the susceptibility of underlying neural volumes to FUS, understanding the functioning of the targeted neuroanatomy and aiding in mechanistic studies of this non-invasive neuromodulation technique.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects3 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlsound only sham
Readout timingonline
Anaesthesiaanaesthetised
Readoutsemg mepfour-limb electromyography (EMG) of triceps brachii and biceps femoris
Direction of effectexcitatoryFUS elicited target-specific four-limb motor (EMG) responses, more effectively than a matched auditory tone or sham stimulus, indicating direct excitatory neuromodulation rather than an auditory startle response.
Adverse eventsnot reportedA thermocouple experiment found a peak subcranial temperature rise of 2.3 ± 0.1°C at the end of the last 300-ms pulse, with no accumulation over successive sonications.

Exposures

Exposure 1: Motor region (M) sonication

Target: motor cortex — “The motor region (M) included most of the motor cortex.
Device: IGT / Imasonic · Imasonic SAS

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,000✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 50%
Sonication duration (s)0.3✓✓
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
Pressure, domain unspecified (kPa)1,760✓✓
Isppa, domain unspecified (W/cm²)97✓✓
Protocol, in the paper’s words

Each target was sonicated 10 times for statistical purposes before repositioning the transducer at the next target. Sonications were applied for 300 ms at 5-s intervals (vs. the 1-s duration at 1-s interval used before) to reduce potential cumulative effects associated with repetitive sonications such as temperature elevation.

Exposure 2: Left/right posterior region (LP/RP) sonication

Target: other — “The two posterior regions were situated entirely in the left or right hemispheres, denoted LP (left posterior) and RP (right posterior).
Device: IGT / Imasonic · Imasonic SAS

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,000✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 50%
Sonication duration (s)0.3✓✓
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
Pressure, domain unspecified (kPa)1,760✓✓
Isppa, domain unspecified (W/cm²)97✓✓
Protocol, in the paper’s words

Each target was sonicated 10 times for statistical purposes before repositioning the transducer at the next target. Sonications were applied for 300 ms at 5-s intervals (vs. the 1-s duration at 1-s interval used before) to reduce potential cumulative effects associated with repetitive sonications such as temperature elevation.

Flags from extraction

  • exposures[0].unspecified_domain.isppa_w_cm2ISPPA is explicitly calculated using the acoustic impedance of brain tissue, suggesting it is intended as an in-situ estimate, but the paper does not explicitly label the pressure/intensity domain (free field vs in situ), so it is recorded as unspecified.
  • exposures[1].target.termsThe LP/RP posterior regions are not named as a specific structure in the target vocabulary; paper associates them qualitatively with midbrain locomotor-control areas without stating precise coordinates in the main text.
  • exposures[0].timing.duty_cycle_pctDuty cycle is computable from pulse length (0.5 ms) and PRF (1 kHz) but is not stated directly by the paper, so left not_reported per protocol.