← Explore

State-dependent neurovascular modulation induced by transcranial ultrasound stimulation

Hang Song, Ruoyu Chen, Liyuan Ren, Junfeng Sun, Shanbao Tong

Medical & Biological Engineering & Computing 2025 · 10.1007/s11517-025-03290-5

rodenthealthyinvasive electrophysiologycerebral haemodynamics

Abstract

Previous studies reported baseline state-dependent effects on neural and hemodynamic responses to transcranial ultrasound stimulation. However, due to neurovascular coupling, neither neural nor hemodynamic baseline alone can fully explain the ultrasound-induced responses. In this study, using a general linear model, we aimed to investigate the roles of both neural and hemodynamic baseline status as well as their interactions in ultrasound-induced responses. Thirty Sprague-Dawley rats were randomly assigned to Hypoxia, Hyperoxia, and Normoxia groups. The baseline states were altered by changing the oxygen concentrations. Micro-electrode and laser speckle contrast imaging were used to record local field potentials and cerebral blood flow during resting, before, and after ultrasound stimulation, respectively. We found that baseline neural activity played a positive role in neural response (Coefficient = 0.634, t = 1.748, p = 0.096, ηp2 = 0.133), but a negative role in hemodynamic response (Coefficient = - 0.060, t = - 1.996, p = 0.060, ηp2 = 0.166). Baseline hemodynamic activity also had a significantly negative correlation with the hemodynamic response (Coefficient = - 0.760, t = - 3.947, p < 0.001, ηp2 = 0.438). This study enriched our understanding of state-dependent effects underlying the neurovascular activation by ultrasound stimulation.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects30 animals
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, cerebral haemodynamics — local field potential in S1 (relative LFP power); laser speckle contrast imaging (relative CBF)
Direction of effectmixed or unclearRelative LFP power rose after TUS in the hyperoxia and normoxia groups (not significant for group interaction); rCBF fell in hypoxia and rose in hyperoxia and normoxia. Baseline neural activity was positively related to the neural response and baseline CBF and LFP were negatively related to the CBF response.
Adverse eventsnot reported

Exposures

Exposure 1: TUS at S1 under hypoxia, hyperoxia and normoxia

Target: primary somatosensory cortex — “S1”
Device: Olympus / Panametrics · Olympus NDT · V318-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)0.4✓✓✓⚑
Pulse repetition frequency (Hz)1,500✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 60%⚑
Sonication duration (s)1✓✓✓⚑
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)8.69✓✓✓⚑
Protocol, in the paper’s words

5 min of stimulation consisting of 1-s sonications (tone burst duration 0.4 ms, PRF 1.5 kHz) with an interstimulus interval of 4 s, delivered through a 3-mm plexiglass collimator.

Flags from extraction

  • n_subjects — 30 rats enrolled; 6 were used in a preliminary experiment and 24 (8 per group) in the formal experiment.
  • n_sessions_per_subject — A single 5-min TUS session per rat is implied by the protocol but the number of sessions is not stated.
  • exposures[0].unspecified_domain.isppa_w_cm2 — Isppa given without stating the medium; a hydrophone measured the field with the collimator attached.
  • exposures[0].timing.duty_cycle_pct — Duty cycle is mentioned but its value is not stated.
  • exposures[0].timing.pulse_duration_ms — Burst rule: TBD 0.4 ms taken as the pulse; sonication duration (SD) 1 s is the train; 'ISI = 4 s' interpretation as gap between sonications is assumed from the protocol.
  • exposures[0].timing.sonication_duration_s — Nested structure: 1-s sonications repeated across a 5-min session with a 4-s ISI.

Notes: Hypoxia, hyperoxia and normoxia were used to change baseline state; all three groups received the same TUS.