Low-intensity transcranial ultrasound stimulation modulates neurovascular coupling in mouse models of Alzheimer’s disease

Xin Li, Qiaoxuan Wang, Mengran Wang, Zhenfang Ma, Yi Yuan

Cerebral Cortex 2024 · 10.1093/cercor/bhae413

rodentalzheimers diseasecerebral haemodynamicsinvasive electrophysiology

Abstract

Neurovascular coupling plays an important role in the progression of Alzheimer's disease. However, it is unclear how ultrasound stimulation modulates neurovascular coupling in Alzheimer's disease. Here, we found that (i) transcranial ultrasound stimulation modulates the time domain and frequency domain characteristics of cerebral blood oxygen metabolism in Alzheimer's disease mice; (ii) transcranial ultrasound stimulation can significantly modulate the relative power of theta and gamma frequency of local field potential in Alzheimer's disease mice; and (iii) transcranial ultrasound stimulation can significantly modulate the neurovascular coupling in time domain and frequency domain induced by forepaw electrical stimulation in Alzheimer's disease mice. It provides a research basis for the clinical application of transcranial ultrasound stimulation in Alzheimer's disease patients.

Abstract via europepmc.

Speciesmouse (APP/PS1 transgenic; C57BL/6 wild-type)

Subjects8, 8swept animals

Sessions per subjectnot reported

Randomisedyes

Blindingnot reported

Sham / controlno treatment control

Auditory controlnot reported

Readout timingonline

Anaesthesiaboth

Readoutscerebral haemodynamics, invasive electrophysiology — optical intrinsic signal imaging (HbR); LFP theta/gamma relative power and sample entropy; neurovascular coupling by Pearson correlation

Direction of effectmixed or unclearTUS before forepaw stimulation increased the HbR response peak and shortened its peak time in AD mice toward healthy values, and lowered theta relative power and neurovascular coupling strength.

Adverse eventsnot reported

Exposures

Exposure 1: TUS to left hippocampus in APP/PS1 mice

Target: hippocampus — “hippocampus”
Device: Olympus / Panametrics · Olympus, USA · V301-SU ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	500	✓✓✓
Pulse duration (ms)	not reportedimplied by duty cycle ÷ PRF: 0.3 ms (not stated by the paper)	⚑
Pulse repetition frequency (Hz)	1,000	✓✓✓
Duty cycle (%)	30	✓✓✓
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 estimate	not 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)	310	✓✓✓⚑

Protocol, in the paper’s words

Stimulation duration 50 ms at PRF 1 kHz and 30% duty cycle, timed by a LABVIEW program with 30 s forepaw electrical stimulation trials, 16 trials per mouse.

Flags from extraction

n_subjects — 16 = AD-TUS (8) + AD-TUS+FES (8) received TUS; 8 wild-type FES-only and 8 AD-FES mice were not sonicated. Group-size text is garbled by extraction.
exposures[0].timing.pulse_duration_ms — Pulse duration not stated; 'stimulation duration 50 ms' is taken as the sonication duration.
exposures[0].timing.sonication_duration_s — SD 50 ms with PRF 1 kHz and DC 30% gives 50 pulses of 0.3 ms by arithmetic; burst rule not resolved from text alone.
exposures[0].unspecified_domain.pressure_kpa — 'Maximum ultrasound pressure 0.31 MPa'; domain not stated.
anaesthesia — Isoflurane for surgery; recordings and TUS in awake restrained mice.