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High-Resolution Transcranial Electrical Simulation for Living Mice Based on Magneto-Acoustic Effect

Xiaoqing Zhou, Shikun Liu, Yuexiang Wang, Tao Yin, Zhuo Yang, Zhipeng Liu

Frontiers in Neuroscience 2019 · 10.3389/fnins.2019.01342

rodenthealthyparkinsons diseasebehaviourinvasive electrophysiology

Abstract

Transcranial electrical stimulation is an important neuromodulation tool, which has been widely applied in the cognitive sciences and in the treatment of neurological and psychiatric diseases. In this work, a novel non-invasive method of transcranial electrical stimulation with high-resolution transcranial magneto-acoustic stimulation (TMAS) method has been tested experimentally in living mice for the first time. It can achieve spatial resolution of 2 mm in the cortex and even in the deep brain regions. The induced electrical field of TMAS was simulated and measured using a test sample. Then, an animal experimental system was built, and the healthy as well as Parkinson's disease (PD) mice were simulated by TMAS in vivo . To investigate the effect of transcranial ultrasound stimulation (TUS) at the same time as TMAS, a TUS group was added in the experiments and its results compared with those of the TMAS group. The results not only demonstrate the high-resolution ability and safety of TMAS, but also show that both TMAS and TUS improved the synaptic plasticity of the PD mice and might improve the spatial learning and memory ability of the healthy mice and the PD mice, although the improvement performance of the TMAS group was superior to that of the TUS-group. Based on the in vivo TMAS studies, we propose that TMAS functions as a dual-mode stimulation combining the electric field of the magneto-acoustic effect and the mechanical force of TUS. Our results also provide an explanation of the mechanism of TMAS. This research suggests that future use of US stimulation in magnetic resonance imaging (MRI)-guided studies should involve careful consideration of the induced magneto-acoustic electrical field caused by the static magnetic field of MRI.

Abstract via europepmc.

Speciesmouse (C57BL)
Subjects3, 3, 6, 6, 4, 4swept animals
Sessions per subject10
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsbehaviour, invasive electrophysiology — elevated plus-maze, open field, Morris water maze; in vivo hippocampal (dentate gyrus) fEPSP recording of LTP and depotentiation
Direction of effectmixed or unclearBoth TMAS (ultrasound plus 0.2 T static field) and ultrasound alone (TUS) improved hippocampal LTP in MPTP mice and might improve water-maze performance relative to sham; TMAS performed better than TUS. Behavioural group sizes were 3 or 4 per group.
Adverse eventsnone observedPD mice were in good physical and mental state during the 10 days of treatment and showed no obvious discomfort after TMAS and TUS.

Exposures

Exposure 1: TUS (and TMAS with 0.2 T magnet) to substantia nigra, 1 MHz, daily for 10 days

Target: substantia nigra — “substantia nigra of the mouse brain”
Device: other named manufacturer · IOA-AC, China · FP-1M

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓✓
Pulse duration (ms)0.2✓✓✓⚑
Pulse repetition frequency (Hz)1✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 0.02%
Sonication duration (s)120✓✓✓
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 estimatemeasurementsingle value
In-situ pressure (kPa)3,000✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.06✓✓✓⚑
Protocol, in the paper’s words

1 MHz pulses with a stated pulse duration of "200 µm" (unit as printed, apparently a typo for a time unit) at 1 Hz PRF; 2 min per session containing 120 pulses, once daily for 10 days. The TMAS arm used the same ultrasound within a 0.2 T static magnetic field; the TUS arm removed the magnet. Mice were under 1% isoflurane.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Text says pulse duration was "200 µm" at 1 Hz PRF; unit is not a time unit (likely microseconds), so not recorded.
  • exposures[0].in_situ.pressure_kpa — Stated intracranial pressure of about 3 MPa looks implausible next to an Ispta of about 60 mW/cm2; recorded as printed.
  • exposures[0].in_situ.ispta_w_cm2 — Ispta given as 60 mW/cm2, converted to W/cm2.
  • n_subjects — Healthy n=9 and PD n=30 are group totals including sham mice; the paper gives no total, and only TMAS and TUS arms (not sham) received ultrasound.
  • exposures[0] — Paper is chiefly about magneto-acoustic stimulation; only the TUS arm (magnet removed) is pure ultrasound, and the TMAS arm shares the same ultrasound parameters. Recorded as one exposure.