Hsueh, Shang-YiShang-YiHsuehLu, Ying-ChangYing-ChangLuLim, JormayJormayLimChu, Ya-CherngYa-CherngChuPEI-HSUAN LINChan, Yen-HuiYen-HuiChanWu, Yu-WeiYu-WeiWuCHEN-CHI WUJAW-LIN WANG2025-08-282025-08-282025-08-0503785955https://www.scopus.com/record/display.uri?eid=2-s2.0-105012313303&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/731686Objectives: Transcranial ultrasound stimulation (TUS) is a non-invasive technique with therapeutic potential for neurodegenerative diseases. Given its increasing therapeutic relevance, it is essential to identify any unintended consequences, especially on vulnerable systems such as the auditory pathway. Specifically, the precise impact of TUS on auditory responses and neural activation patterns within the central auditory system remains unclear. We hypothesized that TUS could indirectly modulate central auditory processing, even at frequencies outside the direct hearing range, leading to observable changes in auditory brainstem responses (ABRs) and neuronal activity in the cochlear nucleus. Design: We analyzed periodic ABR recordings before and after 1 MHz ultrasound stimulation in mice. To investigate the immediate and long-term engram effects of ultrasound stimulation in the cochlear nucleus, we used c-Fos TRAP2 mice. All mice received a 12 kHz pure tone stimulation to establish the tonal signature in the cochlear nucleus. We administered ultrasound stimulation transcranially over the entire brain, covering the region including the cochlear nucleus, either immediately prior to the first tone presentation (ultrasound preconditioning group) or 30 minutes prior to sacrifice (acute ultrasound group) to analyze the long-term and immediate responses to ultrasound stimulation, respectively. A sham control group received only the 12 kHz tone stimulation. Results: Ultrasound stimulation induced latency shifts in ABR recordings. The effect of ultrasound on latency was more pronounced at regions of the auditory pathway farther from the inner ear. A significant increase in immediate neural activation was observed in the acute ultrasound group, while a trend toward an increase in long-term engram effect was seen in the ultrasound preconditioning group. A broader band pattern of neural activation was consistently identified in the cochlear nucleus following TUS. These results suggest that TUS can affect neural activation in the cochlear nucleus, manifesting as ABR latency shifts. Conclusions: This study provides evidence that ultrasound stimulation can induce latency shifts in ABR recordings and alter neuronal activation patterns in the cochlear nucleus, indicating a modulatory effect of ultrasound on the auditory pathway. The observed activation of neurons along the auditory pathway by ultrasound may offer therapeutic opportunities to improve auditory transduction in patients with central auditory pathway dysfunction, such as auditory neuropathy.falseAuditory brainstem responsec-FosCochlear nucleusLatency shiftUltrasound neuromodulation[SDGs]SDG3journal article10.1016/j.heares.2025.1093792-s2.0-105012313303