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Autonomic modulation by low-intensity focused ultrasound stimulation of the vagus nerve

Ning Ji, Yuanheng Li, Jingjing Wei, Fei Chen, Lisheng Xu, Guanglin Li, Wan-Hua Lin

Journal of Neural Engineering 2022 · 10.1088/1741-2552/aca8cd

rodentotherautonomic physiologyhistology molecular

Abstract

Objective. Our previous study has shown that low-intensity focused ultrasound stimulation (FUS) of the vagus nerve could modulate blood pressure (BP), but its underlying mechanisms remain unclear. We hypothesized that low-intensity FUS of the vagus nerve would regulate autonomic function and thus BP. Approach. 17 anesthetized spontaneously hypertensive rats were treated with low-intensity FUS of the left vagus nerve for 15 min each trial. Continuous BP, heart rate, respiration rate (RR), and core body temperature were simultaneously recorded to evaluate the effects on BP and other physiological parameters. Heart rate variability (HRV), systolic BP variability, and baroreflex sensitivity were computed to evaluate the autonomic modulation function. A Control-sham group without stimulation and another Control-FUS group with non-target stimulation were also examined to exclude the influence of potential confounding factors on autonomic modulation. Main results. A prolonged significant decrease in BP, pulse pressure, RR, the normalized low-frequency power of HRV, and the low-to-high frequency power ratio of HRV were found after the low-intensity FUS of the left vagus nerve in comparison with the baseline and those of the control groups, demonstrating that activities of the sympathetic nervous system were inhibited. The prolonged significant increase of the normalized high-frequency power of HRV suggested the activation of parasympathetic activity. Significance. Low-intensity FUS of the left vagus nerve effectively improved the autonomic function by activating parasympathetic efferent and inhibiting sympathetic efferent, which contributes to BP reduction. The findings shed light on the hypotensive mechanism underlying FUS.

Abstract via europepmc.

Speciesrat (spontaneously hypertensive rat)
Subjects17, 12swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer, active control site
Auditory controlcontrol experiment
Readout timingboth
Anaesthesiaanaesthetised
Readoutsautonomic physiology, histology molecular — blood pressure, heart rate, respiration rate, heart rate variability, systolic BP variability, baroreflex sensitivity; H&E staining of vagus nerve
Direction of effectmixed or unclearLeft vagus nerve FUS lowered blood pressure and respiration rate, reduced normalised low-frequency HRV power and LF/HF ratio (sympathetic inhibition) and raised normalised high-frequency HRV power (parasympathetic activation) versus controls; effects persisted about 30 min after FUS.
Adverse eventsnone observedH&E histology of the sonicated vagus nerve showed normal histology without necrosis or inflammatory response.

Exposures

Exposure 1: FUS of the left cervical vagus nerve

Target: vagus nerve — “left vagus nerve”
Device: not reported

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)3,700✓✓✓
Pulse duration (ms)2✓✓✓
Pulse repetition frequency (Hz)100✓✓✓
Duty cycle (%)20pulse duration × PRF gives 20%✓✓✓
Sonication duration (s)1✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)18✓✓✓
Free-field Ispta (W/cm²)0.6✓✓✓⚑
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

100 Hz PRF, 20% duty cycle, 2 ms tone burst, 1 s sonication, inter-stimulation interval of 6 s; each trial had 10 min baseline, 15 min ultrasound stimulation and 30 min recovery. Control-sham: transducer placed on the nerve with FUS off; Control-FUS: FUS to the left upper leg.

Flags from extraction

  • n_subjects — 50 rats were allocated to three groups; 21 (Control-sham) received no ultrasound, 12 received FUS at the leg and 17 at the vagus nerve. Value is enrolled total.
  • exposures[0].free_field.ispta_w_cm2 — Stated Ispta 0.6 W/cm2 is not what 20% duty cycle times 18 W/cm2 would give; the 1 s on / 6 s interval pattern may explain it. Recorded as stated.
  • auditory_control — Paper states the control groups were meant to exclude auditory and non-target confounds; no dedicated auditory control (masking, deafening) is described.
  • exposures[0].device.family — Transducer maker not named; described only by frequency, diameter and focal length; refers to a previous paper.
  • n_sessions_per_subject — Trials are counted per group (25, 25, 15 trials) and not per rat.