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Time–frequency cross-coupling between cortical low-frequency neuronal calcium oscillations and blood oxygen metabolism evoked by ultrasound stimulation

Zhaocheng Su, Jiaqing Yan, Hui Ji, Mengyang Liu, Xiangjian Zhang, Xiaoli Li, Yi Yuan

Cerebral Cortex 2023 · 10.1093/cercor/bhac370

rodenthealthycerebral haemodynamicsother

Abstract

Low-intensity transcranial ultrasound stimulation (TUS) can modulate the coupling of high-frequency (160-200 Hz) neural oscillations and cerebral blood oxygen metabolism (BOM); however, the correlation of low-frequency (0-2 Hz) neural oscillations with BOM in temporal and frequency domains under TUS remains unclear. To address this, we monitored the TUS-evoked neuronal calcium oscillations and BOM simultaneously in the mouse visual cortex by using multimodal optical imaging with a high spatiotemporal resolution. We demonstrated that TUS can significantly increase the intensity of the neuronal calcium oscillations and BOM; the peak value, peak time, and duration of calcium oscillations are functionally related to stimulation duration; TUS does not significantly increase the neurovascular coupling strength between calcium oscillations and BOM in the temporal domain; the time differences of the energy peaks between TUS-induced calcium oscillations and BOM depend on their spectral ranges; the frequency differences of the energy peaks between TUS-induced calcium oscillations and BOM depend on their time ranges; and TUS can significantly change the phase of calcium oscillations and BOM from uniform distribution to a more concentrated region. In conclusion, ultrasound stimulation can evoke the time-frequency cross-coupling between the cortical low-frequency neuronal calcium oscillations and BOM in mouse.

Abstract via europepmc.

Speciesmouse (Thy1-GCaMP6f transgenic)
Subjects15 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlcontrol experiment
Readout timingonline
Anaesthesiaanaesthetised
Readoutscerebral haemodynamics, other — widefield GCaMP6f calcium fluorescence imaging; intrinsic signal optical imaging of HbO, HbR, HbT
Direction of effectexcitatoryTUS increased neuronal calcium oscillation intensity and HbO/HbT and decreased HbR in the visual cortex; calcium peak value, peak time and duration increased with stimulation duration.
Adverse eventsnot reported

Exposures

Exposure 1: TUS of mouse visual cortex, stimulation duration 0.3-0.7 s

Target: primary visual cortex — “mouse visual cortex”
Device: Olympus / Panametrics · Olympus · V323-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.1 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)10✓✓✓
Sonication duration (s)0.3, 0.7swept✓✓✓⚑
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)450✓?⚑
Isppa, domain unspecified (W/cm²)6.75✓?
Protocol, in the paper’s words

500 kHz, 1 kHz PRF, 10% duty cycle; stimulation duration 0.4 s in the main protocol and varied from 0.3 to 0.7 s in 0.1 s steps; one stimulus every 10 s; 8 trials averaged, repeated after 30 min.

Flags from extraction

  • n_subjects — 15 total: 9 normal-hearing, 6 chemically deafened.
  • exposures[0].timing.sonication_duration_s — Range 0.3-0.7 s recorded as stated; text says 0.4 s as the standard duration.
  • exposures[0].unspecified_domain.pressure_kpa — 0.45 MPa and Isppa 6.75 W/cm2; hydrophone measurement 'under the skull' is mentioned but pressure domain not explicitly assigned.
  • exposures[0].timing.pulse_duration_ms — Not stated; duty cycle and PRF given, but not computed here.