Modulation of rapid eye movement sleep deprivation via transcranial ultrasound stimulation of the basal forebrain in mice
Yue Wu, Haiqing Wang, Mengke Wang, Pengyu Ren, Siyuan Zhang
Ultrasonics 2026, 108282 · 10.1016/j.ultras.2026.108282
Abstract
This study presents a strategy of non‑invasive transcranial ultrasound stimulation (TUS) to mitigate sleep insufficiency. Mice were subjected to 20 h of sleep deprivation, while receiving 10 min of TUS of the basal forebrain for 7 days. Sleep architecture was evaluated by electroencephalographic analysis, while anxiety-like behavior and cognitive performance were assessed using open field testing and Y-maze. Hippocampal neuronal integrity was examined by Nissl staining, and serum cortisol levels was assessed by ELISA, whereas basal forebrain cholinergic activation was analyzed using c-Fos immunofluorescence. TUS significantly increased rapid eye movement (REM) sleep compared with the sleep-deprived group (14.97 ± 1.05% vs. 10.86 ± 1.11%, P < 0.05), while non-rapid eye movement-related delta power rose to 130.77% of normal control levels (P < 0.0001) and REM-related theta power was enhanced (P < 0.05). TUS improved cognitive performance, increasing Y-maze alternation rate to 61.42 ± 1.31% versus 50.05 ± 1.59% in sleep-deprived mice (P < 0.001). Histological analysis demonstrated marked neuroprotection, with TUS significantly restoring hippocampal neuronal counts in the cornu ammonis 1 and dentate gyrus. In addition, serum cortisol levels were elevated toward normal values (P < 0.05), accompanied by increased c-Fos expression, suggesting enhanced basal forebrain neuronal activity and potential cholinergic involvement. These findings suggest that TUS provides a novel non-pharmacological treatment strategy targeting the basal forebrain in the sleep deprivation mouse model.
Abstract via europepmc.
Exposures
Exposure 1: TUS of the bilateral medial basal forebrain in sleep-deprived mice
Target: basal forebrain — “bilateral medial basal forebrain (AP = +0.24 mm, ML = ±0.25 mm, DV = -5.00 mm relative to bregma)”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 250 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 270 | ✓✓✓⚑ |
|---|---|---|
| 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 |
The total sonication duration (TSD) was 200 ms, with an inter-stimulation interval (ISI) of 5 s. The US group received ultrasound stimulation for 10 min per day while the mice were sleep deprived, for 7 consecutive days.
Flags from extraction
n_subjects— Main group-design statement gives n=8 per group, but several figure legends report smaller subsample sizes for specific assays (e.g., n=5 for EEG/behaviour, n=3 for cortisol); n=8 (the ultrasound-stimulated US group) is used here.exposures[0].device— The transducer is described only as 'a small 1 MHz focused transducer' with no manufacturer or model given.exposures[0].free_field.pressure_kpa— Only negative peak pressure and mechanical index are reported; no ISPPA/ISPTA intensity values are given.