High-Frequency Focused Ultrasound Directly Activates the Auditory Midbrain and Protects Against Noise-Induced Hearing Loss in Guinea Pigs

Abstract

Although focused ultrasound (FUS) offers promising opportunities for neuromodulation, its ability to activate central auditory neurons remains uncertain. We targeted the central nucleus of the inferior colliculus (CNIC) in anesthetized guinea pigs using 20-MHz FUS while recording cochlear and cortical activity. Consistent with previous studies, FUS delivered through a small craniotomy evoked cortical responses through indirect cochlear activation, potentially mediated by skull mechanical coupling. However, under conditions that minimized cochlear interaction, FUS induced c-Fos expression in the CNIC and auditory cortex, suggesting direct central activation of the auditory afferent pathway. FUS additionally engaged the auditory efferent system, presumably through medial olivocochlear neurons. FUS delivered before acoustic trauma nearly prevented noise-induced hearing loss, limiting threshold shifts to <10 dB compared with ~60 dB in controls. Gentamicin abolished both efferent modulation and protection, implicating cochlear efferent mechanisms. Together, these findings support FUS for auditory neuromodulation and cochlear protection against acoustic injury.