Regulation of Circadian Rhythm Disruption in Mice via Transcranial Low-Intensity Focused Ultrasound Stimulation Targeting the Suprachiasmatic Nucleus
Haiqin Wang, Dapeng Li, Mengke Wang, Baochen Zhang, Zhou Jiang, Yue Wu, Jiawei Duan, Dong Huang, Pengyu Ren, Siyuan Zhang
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2025 · 10.1109/tnsre.2025.3626143
Abstract
Circadian rhythm disruption (CRD) is a critical contributor to sleep, metabolic, and neuropsychiatric disorders. Ultrasound (US) stimulation represents a non-invasive neuromodulatory modality, yet its impact on CRD remains unexplored. This study is the first to propose and systematically assess the effects of transcranial low-intensity focused ultrasound (LIFU) stimulation targeting the suprachiasmatic nucleus (SCN) in a chronic jet lag mouse model. Circadian and anxiety-related behaviors were evaluated through spontaneous locomotor activity monitoring and open field testing. Plasma melatonin and cortisol levels were quantified via ELISA, and neuronal activity in the SCN, dorsomedial hypothalamus (DMH), and subparaventricular zone (SPZ) was assessed using c-Fos immunofluorescence. Results revealed that US stimulation markedly reduced the phase difference in the US-SCN group to -2.6 h, in contrast to -7.15 h in the CJL group, indicating enhanced circadian alignment with the normal control group in the US-SCN. In the US-SCN group, melatonin and cortisol levels significantly decreased from 214.70 $~\pm ~$ 3.54 pg/mL and 217.21 $~\pm ~$ 5.62 pg/mL to 172.45 $~\pm ~$ 10.16 pg/mL (p = 0.001) and 187.35 $~\pm ~$ 2.57 pg/mL (p = 0.002), respectively. Additionally, anxiety-like behaviors were alleviated in the US-SCN group, as evidenced by a 61.40% increase in the time spent exploring the center zone. Neuronal activity in the SCN, DMH, and SPZ was significantly enhanced. Histological analysis confirmed no tissue damage following LIFU stimulation, demonstrating its safety. LIFU stimulation of the SCN effectively alleviates CRD. This non-invasive approach offers a promising therapeutic strategy for CRD and advancing neuromodulation-based chronotherapy.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to SCN
Target: suprachiasmatic nucleus — “the suprachiasmatic nucleus (SCN)”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 250 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 350 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 430 | ✓?⚑ |
Total stimulation 10 minutes, pulse trains every 5 s; each train 200 ms with 2 ms tone bursts at PRF 250 Hz (4 ms period); daily in the morning for three consecutive days.
Flags from extraction
n_subjects— n=8 per group for three groups; only the US-SCN group (8) was sonicated, the safety-assessment cohort size is not stated.exposures[0].timing.duty_cycle_pct— Duty cycle not stated.exposures[0].unspecified_domain.pressure_kpa— 0.43 MPa described as peak acoustic pressure at the skull surface; domain not otherwise stated.exposures[0].in_situ.pressure_kpa— 0.35 MPa obtained by the authors from an estimated 18% transcranial attenuation (derating), not measured.exposures[0].device.family— No transducer maker named; only PZT-4 material, 19 mm diameter.anaesthesia— Whether mice were awake or anaesthetised during sonication is not stated.