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Low-intensity ultrasound stimulation modulates time-frequency patterns of cerebral blood oxygenation and neurovascular coupling of mouse under peripheral sensory stimulation state

Yi Yuan, Qianqian Wu, Xingran Wang, Mengyang Liu, Jiaqing Yan, Hui Ji

NeuroImage 2023 · 10.1016/j.neuroimage.2023.119979

rodenthealthycerebral haemodynamicsinvasive electrophysiology

Abstract

Previous studies have demonstrated that transcranial ultrasound stimulation (TUS) not only modulates cerebral hemodynamics, neural activity, and neurovascular coupling characteristics in resting samples but also exerts a significant inhibitory effect on the neural activity in task samples. However, the effect of TUS on cerebral blood oxygenation and neurovascular coupling in task samples remains to be elucidated. To answer this question, we first used forepaw electrical stimulation of the mice to elicit the corresponding cortical excitation, and then stimulated this cortical region using different modes of TUS, and simultaneously recorded the local field potential using electrophysiological acquisition and hemodynamics using optical intrinsic signal imaging. The results indicate that for the mice under peripheral sensory stimulation state, TUS with a duty cycle of 50% can (1) enhance the amplitude of cerebral blood oxygenation signal, (2) reduce the time-frequency characteristics of evoked potential, (3) reduce the strength of neurovascular coupling in time domain, (4) enhance the strength of neurovascular coupling in frequency domain, and (5) reduce the time-frequency cross-coupling of neurovasculature. The results of this study indicate that TUS can modulate the cerebral blood oxygenation and neurovascular coupling in peripheral sensory stimulation state mice under specific parameters. This study opens up a new area of investigation for potential applicability of TUS in brain diseases related to cerebral blood oxygenation and neurovascular coupling.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects12 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutscerebral haemodynamics, invasive electrophysiology — optical intrinsic signal imaging of cerebral blood oxygenation; LFP; neurovascular coupling
Direction of effectmixed or unclearWith simultaneous forepaw electrical stimulation, TUS at 50% duty cycle enhanced the blood-oxygenation signal and reduced evoked-potential time-frequency power; 5% duty cycle and a 1 s delayed TUS had little effect.
Adverse eventsnot reportedEstimated maximum temperature rise from the stated intensity and duration was about 6e-3 C.

Exposures

Exposure 1: TUS combined with forepaw electrical stimulation (modes 2 and 3)

Target: somatosensory cortex — “mouse sensory cortex”
Device: not reported

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)50, 5swept✓✓✓⚑
Sonication duration (s)0.3, 0.6, 0.9swept✓✓✓⚑
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)550✓✓✓⚑
Isppa, domain unspecified (W/cm²)10.1✓✓✓
Protocol, in the paper’s words

500 kHz, PRF 1 kHz, 300 ms stimulation, duty cycle 50% or 5%, delivered simultaneously with forepaw electrical stimulation (mode 2) or lagging it by 1 s (mode 3); extra groups used 600 and 900 ms durations at 5%.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpa — Maximum pressure 0.55 MPa and Isppa 10.1 W/cm2 given without stating medium or skull path.
  • exposures[0].timing.duty_cycle_pct — Duty cycle 50% and 5% are separate groups; 50% mode also used with a 1 s delay.
  • exposures[0].target.terms — Paper says it did not target specific brain regions; stimulated the sensory cortex region identified by forepaw stimulation, coordinates AP -3.8, ML 2.5.
  • exposures[0].timing.sonication_duration_s — Two additional groups (n = 5) used 600 and 900 ms in mode 2 (5%); only 300 ms recorded.
  • exposures[0].device — Transducer not described; refers to a previous study's setup.