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The Effect of Low-Intensity Transcranial Ultrasound Stimulation on Behavior in a Mouse Model of Parkinson’s Disease Induced by MPTP

Yi Yuan, Zhe Zhao, Zhijie Wang, Xingrang Wang, Jiaqing Yan, Xiaoli Li

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2020, 28, 1017-1021 · 10.1109/tnsre.2020.2978865

rodentparkinsons diseasebehaviour

Abstract

This study investigated the effects of low-intensity transcranial ultrasound stimulation (TUS) on behavior in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD mouse model was induced by consecutive injecting the mice with MPTP for 7 days. When the animal model is completed, we performed behavioral tests including the wire hanging test, open field test and forced swimming test on day 1, 2, 3, 4, 7, 14 during 2 weeks. Simultaneously, the ultrasound was used to stimulate the brain tissue of the mice daily for these 2 weeks. The data were analyzed to examine treatment effects. When the PD+TUS and PD+Sham groups were compared, the behavior of the PD+TUS mice was better on the fourth day after TUS (*p<0.05) and had further improved on the fourteenth day of TUS (**p<0.01). These results demonstrate that TUS can improve behavior in mice with MPTP-induced PD. The treatment effect gradually improved as the TUS duration increased.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects8 animals
Sessions per subject14
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsbehaviourwire hanging test, open field test, forced swimming test
Direction of effectnot assessedTUS improved wire-hanging, open-field, and forced-swimming behavioral scores in the PD+TUS group relative to PD+Sham from day 4 onward, with no direct neurophysiological measure of excitation/inhibition reported.
Adverse eventsnot reportedAuthors estimated the maximum temperature rise from ultrasound to be far below the threshold for thermal bioeffects, based on the maximum intensity and pulse duration used.

Exposures

Exposure 1: PD+TUS group, single stimulation protocol

Target: subthalamic nucleus — “brain tissue without motor cortex; the subthalamic nucleus (STN) is one of nuclei in brain tissue covered by the ultrasound spot
Device: Olympus / Panametrics · Olympus, USA · V301-SU

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.05 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)5✓✓
Sonication duration (s)0.05✓✓
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)390✓✓
Isppa, domain unspecified (W/cm²)5.1✓✓
Ispta, domain unspecified (W/cm²)0.255✓✓
Protocol, in the paper’s words

The interstimulus interval was 1 s, and the total stimulation time was 5 minutes for each stimulus. TUS was performed in the PD mice daily for 2 weeks.

Flags from extraction

  • exposures[0].targetExact stimulation target is not given with stereotaxic coordinates; paper only states brain tissue excluding motor cortex, with STN noted as one nucleus covered by the ultrasound spot.
  • exposures[0].unspecified_domain.pressure_kpaPaper does not state whether the measured pressure/intensity was measured in free field/water or in situ; hydrophone measurement setup relative to the animal is not specified.
  • exposures[0].timing.pulse_duration_msPaper gives a separate 'stimulation duration (SD)' of 50 ms and a PRF/duty cycle but never states a distinct pulse duration; not computed per protocol (would be 0.05 ms from duty/PRF).
  • direction_of_effectOnly behavioral outcomes were assessed; no neurophysiological measure of excitatory/inhibitory direction was reported.