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Noninvasive Focused Ultrasound Stimulation Can Modulate Phase-Amplitude Coupling between Neuronal Oscillations in the Rat Hippocampus

Yi Yuan, Jiaqing Yan, Zhitao Ma, Xiaoli Li

Frontiers in Neuroscience 2016 · 10.3389/fnins.2016.00348

rodenthealthyinvasive electrophysiology

Abstract

Noninvasive focused ultrasound stimulation (FUS) can be used to modulate neural activity with high spatial resolution. Phase-amplitude coupling (PAC) between neuronal oscillations is tightly associated with cognitive processes, including learning, attention, and memory. In this study, we investigated the effect of FUS on PAC between neuronal oscillations and established the relationship between the PAC index and ultrasonic intensity. The rat hippocampus was stimulated using focused ultrasound at different spatial-average pulse-average ultrasonic intensities (3.9, 9.6, and 19.2 W/cm(2)). The local field potentials (LFPs) in the rat hippocampus were recorded before and after FUS. Then, we analyzed PAC between neuronal oscillations using a PAC calculation algorithm. Our results showed that FUS significantly modulated PAC between the theta (4-8 Hz) and gamma (30-80 Hz) bands and between the alpha (9-13 Hz) and ripple (81-200 Hz) bands in the rat hippocampus, and PAC increased with incremental increases in ultrasonic intensity.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects6 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology — LFP phase-amplitude coupling index
Direction of effectmixed or unclearPhase-amplitude coupling between theta-gamma and alpha-ripple bands increased with ultrasonic intensity relative to the pre-FUS control.
Adverse eventsnot reportedAuthors judged the dose safe because the maximum intensity was below diagnostic imaging limits; no tissue assessment reported.

Exposures

Exposure 1: FUS to rat hippocampus at 3.9, 9.6, 19.2 W/cm2

Target: hippocampus — “rat hippocampus”
Device: not reported

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,500✓✓✓
Pulse duration (ms)0.0016✓✓✓⚑
Pulse repetition frequency (Hz)500✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 0.08%
Sonication duration (s)0.16✓✓✓⚑
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
Isppa, domain unspecified (W/cm²)3.9, 9.6, 19.2swept✓✓✓⚑
Protocol, in the paper’s words

A single stimulation consisted of 4-cycle (1.6 us) ultrasound pulses at a PRF of 500 Hz and a duration of 160 ms (80 repetitions). Transducer coupled via a plastic cone and gel; LFPs recorded before and after FUS.

Flags from extraction

  • exposures[0].unspecified_domain.isppa_w_cm2 — Paper calls these 'spatial-average pulse-average' intensities measured with a sound power meter of 9.5 mm diameter; the metric is not Isppa and the medium is not stated.
  • exposures[0].timing.pulse_duration_ms — Stated as 4 cycles (1.6 us); converted to ms.
  • exposures[0].timing.sonication_duration_s — Duration of 160 ms (80 repetitions) converted to s; inter-stimulus interval and number of stimulations not stated.
  • exposures[0].device.family — Transducer maker not named; only the Ultratek driver card.