Modulation of rapid eye movement sleep deprivation via transcranial ultrasound stimulation of the basal forebrain in mice.

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.