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Transcranial Ultrasound Stimulation Improves Memory Performance of Parkinsonian Mice

Zhe Zhao, Hui Ji, Jiamin Pei, Jiaqing Yan, Xiangjian Zhang, Yi Yuan, Mengyang Liu

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2024 · 10.1109/tnsre.2024.3378109

rodentparkinsons diseasehealthybehaviourinvasive electrophysiology

Abstract

Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD). Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation can significantly suppress the motor symptoms of PD. However, whether ultrasound stimulation can improve cognitive ability in PD and the related neural oscillation mechanism remain unclear to date. To evaluate the effect of ultrasound stimulation on memory ability in PD and explore its neural oscillation mechanism. Ultrasonography was used for 7-day stimulation of the CA1 in transgenic mice with PD. The working memory ability of the PD mice was then tested using novel object discrimination, and the local field potential and spikes in the mice CA1 were recorded at the same time as in the behavioral test. We found that ultrasound stimulation of the PD mice CA1 for 4 days: 1) significantly increased their learning and memory ability, although the learning and memory ability on the 7th day after the stimulation stopped was not significantly different from that before stimulation (P>0.05); 2) significantly increased the relative power of theta, low gamma, and high gamma frequency bands of the local field potential, and the phase amplitude coupling strength between theta and low gamma and between theta and high gamma; and 3) modulated the phase-locking angle between the spike of interneuron and theta wave to a 180°-360° rise cycle. Transcranial ultrasound stimulation can improve the learning and memory abilities of PD mice, and evoking neural oscillations in the CA1 is the potential mechanism.

Abstract via europepmc.

Speciesmouse (C57BL/6; C57BL/6J-TgN alpha-synuclein A53T)
Subjects6, 6swept animals
Sessions per subject7
Randomisednot reported
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingnot reported
Anaesthesiaawake
Readoutsbehaviour, invasive electrophysiology — novel object recognition; CA1 LFP, spikes
Direction of effectmixed or unclearTUS of CA1 increased novel object exploration, relative LFP power in theta and gamma bands and theta-gamma coupling in PD and normal mice from day 4; effects returned toward baseline by day 14.
Adverse eventsnone observedHE staining showed no damage except minor damage at the electrode implantation site.

Exposures

Exposure 1: CA1 stimulation, 1 MHz

Target: CA1 — “CA1 region (hippocampus)”
Device: Olympus / Panametrics · Olympus, USA · V301-SU focused probe ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓✓
Pulse duration (ms)50✓✓✓⚑
Pulse repetition frequency (Hz)1✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)300✓✓✓⚑
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)510✓✓✓⚑
Protocol, in the paper’s words

Fundamental frequency 1 MHz, 50000 cycles per pulse, PRF 1 Hz, duty cycle 5%, stimulation duration (SD) 50 ms. Each stimulation lasted 5 minutes then paused 5 minutes, 3 cycles in total (25 minutes), once daily for 7 days.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Paper gives 'stimulation duration (SD)=50 ms' with 50000 cycles at 1 MHz, PRF 1 Hz and duty cycle 5%; taken as the pulse duration because 5%/1 Hz = 50 ms (resolved by arithmetic).
  • exposures[0].timing.sonication_duration_s — Value 300 s is the 5-minute stimulation block (3 blocks separated by 5-minute pauses), converted from the text.
  • exposures[0].unspecified_domain.pressure_kpa — 'Maximum sound pressure' 0.51 MPa given without stating the domain; a COMSOL simulation is mentioned separately.
  • n_subjects — 12 wild-type and 6 transgenic mice are stated; non-stimulated normal controls exist, so the number actually sonicated is not stated; group sizes of 6 per group are used in the results.
  • readout_timing — Whether LFP and behaviour were recorded during or after sonication on test days is not stated in the text.
  • direction_of_effect — Effects are on memory and LFP power; direction in terms of excitation or inhibition is not stated.
  • sham_type — Non-stimulated normal mice served as the comparison group; no sham device arm described.