Theta-gamma phase-amplitude coupling as a promising neurophysiological biomarker for evaluating the efficacy of low-intensity focused ultrasound stimulation on vascular dementia treatment
Faqi Wang, Jing Ren, Qiuquan Cai, Rong Liang, Ling Wang, Qing Yang, Yutao Tian, Chenguang Zheng, Jiajia Yang, Dong Ming
Experimental Neurology 2025 · 10.1016/j.expneurol.2025.115237
Abstract
Low-intensity focused ultrasound stimulation (LIFUS) has garnered attention for its potential in vascular dementia (VD) treatment. However, the lack of sufficient data supporting its efficacy and elucidating its mechanisms of action limits its further clinical translation and application. Considerable researches support the idea that LIFUS can improve the disturbance of neural oscillation modes caused by a variety of neurological diseases. However, the effect of LIFUS on neural oscillation modes in VD remains unclear. Therefore, this study aims to investigate the therapeutic effects of LIFUS on neural oscillation modes in VD. To achieve this purpose, the VD model was established via the bilateral common carotid artery occlusion, followed by two weeks of LIFUS treatment targeting the bilateral hippocampus. The therapeutic effects of LIFUS were evaluated by behavioral tests and cerebral blood flow measurement. Electrophysiological signals were recorded from the hippocampal CA1 and CA3 and medial prefrontal cortex (mPFC). The results indicated LIFUS could effectively improve cognitive dysfunction in VD rats. The underlying electrophysiological mechanisms involved the restoration of phase-amplitude coupling (PAC) of theta-gamma oscillations within both the CA3-CA1 local circuit and the hippocampus-mPFC cross-brain circuit. Classification results based on PAC characteristics suggested that PAC metrics are effective for evaluating the efficacy of LIFUS in treating VD, with optimal recognition performance observed in the hippocampus-mPFC cross-brain circuit. Our findings provide neuroelectrophysiological insights into the mechanisms of LIFUS in VD treatment and propose a promising diagnostic biomarker for evaluating LIFUS efficacy in future applications.
Abstract via europepmc.
Exposures
Exposure 1: LIFUS to bilateral hippocampus, 1 MHz
Target: hippocampus — “bilateral hippocampus”
Device: Olympus / Panametrics · Olympus · A303s ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 40 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 4% | ⚑ |
| Sonication duration (s) | 10 | ✓✓✓⚑ |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.1 | ✓✓✓⚑ |
1-ms pulses at 25 ms repetition interval (40 Hz) in 10-s pulse trains repeated every 20 s for 10 min; in the VD+LIFUS group 10 min on each side daily for two weeks.
Flags from extraction
n_subjects— 6 normal rats received acute LIFUS and 26 VD rats received two weeks of LIFUS; the total exposed is not stated, so the group sizes are listed.n_sessions_per_subject— Daily for two weeks is stated in words; no session count given.exposures[0].unspecified_domain.ispta_w_cm2— Ispta 100 mW/cm2 converted to 0.1 W/cm2; medium not stated though field measured with collimator attached.exposures[0].timing.duty_cycle_pct— Duty cycle not stated.exposures[0].timing.sonication_duration_s— 10-s pulse train, repeated every 20 s for 10 min (Table 1).sham_type— Sham: transducer positioned 10 cm from the rat's head without contact, other procedures identical.
Notes: The behavioural, CBF and VD model methods cite the authors' earlier papers; whether any of the exposure was already reported there is not stated.