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Comparison of Electrical and Ultrasound Neurostimulation in Rat Motor Cortex

Daniel W. Gulick, Tao Li, Jeffrey A. Kleim, Bruce C. Towe

Ultrasound in Medicine & Biology 2017 · 10.1016/j.ultrasmedbio.2017.08.937

rodenthealthybehaviouremg mep

Abstract

Ultrasound (US) is known to non-invasively stimulate and modulate brain function; however, the mechanism of action is poorly understood. This study tested US stimulation of rat motor cortex (100 W/cm 2 , 200 kHz) in combination with epidural cortical stimulation. US directly evoked hindlimb movement. This response occurred even with short US bursts (3 ms) and had short latency (10 ms) and long refractory (3 s) periods. Unexpectedly, the epidural cortical stimulation hindlimb response was not altered during the 3-s refractory period of the US hindlimb response. This finding suggests that the US refractory period is not a general suppression of motor cortex, but rather the recovery time of a US-specific mechanism.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects4 animals
Sessions per subject3
Randomisedyes
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsbehaviour, emg mepaccelerometer-based limb/scrotum movement; hindlimb EMG
Direction of effectmixed or unclearDirect US bursts to motor cortex excited hindlimb/scrotum movement (excitatory), while concurrent US significantly suppressed the long-term epidural-cortical-stimulation-evoked motor response (inhibitory); short-term (single paired-pulse) modulation of the ECS response was not significant.
Adverse eventsnone observedUS heating in motor cortex averaged 1.8 +/- 0.6 degC (peak ~3 degC) using a cortical thermocouple; no gross behavioral changes from repeated stimulation were observed.

Exposures

Exposure 1: US stimulation of motor cortex (US/ECS interaction and EMG-latency protocols)

Target: motor cortex — “rat motor cortex
Device: custom-built

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)200✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)0.3, 0.003swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)4.5, 0.009swept✓✓
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

The US power was delivered in bursts of 500-us pulses every 1 ms (50% duty at a 1-kHz pulse rate). For the US-ECS interaction experiment, the 50% duty US bursts were 300 ms in duration at 0.5 Hz. For the EMG latency measurement, the US bursts were only 3 ms (4 pulses), repeated every 10 s. Burst interval for the US/ECS interaction experiment ranged 1-10 s (mean 2 s, Table 1).

Flags from extraction

  • n_subjectsPaper never states a single total: 4 array-implanted rats were used for the modulation/direct-response experiments, a separate group of 3 non-implanted rats was used only for temperature measurement, and EMG latency was measured in 2-3 rats (unclear overlap with the primary 4); left not_reported rather than guess a sum.
  • exposures[0].free_field.isppa_w_cm2Paper reports 'SPTP' (spatial-peak time-peak) rather than the conventional ISPPA (spatial-peak pulse-average); mapped to isppa_w_cm2 as the closest standard quantity.
  • exposures[0].free_fieldThe 100 W/cm2 power density was derived from a water-tank hydrophone/force-balance calibration, then applied in vivo through a craniotomy with no skull in the beam path; recorded as free_field since the paper never states an independently measured or simulated in-brain value.
  • sham_typeStudy has no designed sham/placebo arm for TUS itself; the 'no-US' ECS-only blocks were used as the comparison condition, classified here as no_treatment_control as the closest vocabulary fit.
  • randomisedRandomisation described is of trial order (which ECS pulses were preceded by a US burst) within-subject, not random allocation of subjects to groups.