Noninvasive acoustic vagus nerve stimulation modulates Emotion-Related brain networks
Yiyue Zhu, Houminji Chen, Qianlin Xie, Chuanao Lei, Zhengrong Lin, Long Meng, Lili Niu
Ultrasonics 2027 · 10.1016/j.ultras.2026.108294
Abstract
The vagus nerve, a critical bidirectional pathway linking the central nervous system and peripheral organ systems, plays a core role in emotional regulation. Here, we introduce a noninvasive acoustic vagus nerve stimulation (aVNS) paradigm and systematically characterize its modulatory effects on emotion-related brain circuitry using in vivo fiber photometry, behavioral assays, and transcriptomic profiling. The pulsed aVNS protocol was defined as follows: fundamental frequency = 1 MHz, sonication duration = 1 s, inter-stimulus interval = 9 s, pulse repetition frequency = 100 Hz, tone-burst duration = 0.5 ms, duty cycle = 5 %, and acoustic pressure = 3 MPa. Acoustic field mapping confirmed a spatially confined ultrasound beam, supporting localized stimulation of the cervical vagus nerve region. In vivo calcium imaging revealed robust aVNS-evoked neural responses across multiple emotion-associated brain regions, with the medial prefrontal cortex (mPFC) showing the strongest response magnitude, as indicated by significantly increased area under the curve values during both the stimulation period (0-1 s, p = 0.0156) and the post-stimulation period (1-10 s, p = 0.0156). Response-profile and inter-regional similarity analyses further demonstrated that aVNS organized distributed neural responses into a coordinated network-level activation pattern rather than inducing isolated regional excitation. Behaviorally, aVNS alleviated anxiety-like and depressive-like behaviors in acute lipopolysaccharide-treated mice (0.5 mg/kg), as shown by increased open-arm exploration in the elevated plus maze (EPM; p = 0.0018) and reduced immobility in the tail suspension test (TST; p = 0.0045), as well as in chronic restraint stress mice (6 h/day for 28 consecutive days), as shown by increased open-arm exploration (p = 0.0167) and reduced immobility time (p = 0.0057). Bulk RNA sequencing further showed that repeated aVNS partially reversed stress-induced transcriptional alterations in the mPFC, particularly inflammation-related signatures. Together, these findings demonstrate that noninvasive aVNS modulates emotion-related brain networks and provide neural, behavioral, and molecular evidence supporting its potential for intervention in emotional dysfunction.
Abstract via europepmc.
Exposures
Exposure 1: aVNS to left cervical vagus nerve
Target: vagus nerve — “left cervical VN region”
Device: Olympus / Panametrics · NDT, USA · IBP0106 SF-1.75 in focused transducer with custom collimator ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓⚑ |
| Sonication duration (s) | 1 | ✓✓✓ |
| 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) | 3,000 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.365 | ✓✓✓⚑ |
1 s sonication followed by a 9 s inter-stimulus interval; 15 min of aVNS in LPS mice; 7 consecutive days of aVNS in chronic restraint stress mice.
Flags from extraction
exposures[0].timing.duty_cycle_pct— Abstract, PCD methods and Discussion state 5% duty cycle; Section 2.2 states 10%. 0.5 ms x 100 Hz = 5%; recorded 5.n_subjects— Group sizes vary by experiment (n = 5-7 per photometry region, n = 9 per behavioural group, n = 3 per RNA-seq group); no total stated.exposures[0].unspecified_domain.pressure_kpa— 3 MPa stated as acoustic pressure without domain; hydrophone mapping was in water but the pressure is not explicitly attributed to it.exposures[0].unspecified_domain.ispta_w_cm2— Intensity described as 'calculated' Ispta of 365.26 mW/cm2; domain not stated.n_sessions_per_subject— Varies by experiment (single 15 min session in LPS, 7 days in CRS); not a single number.