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Ultrasound (US) can noninvasively activate intact brain circuits, making it a promising neuromodulation technique. However, little is known about the underlying mechanism. Here, we apply transcranial US and perform brain mapping studies in guinea pigs using extracellular electrophysiology. We find that US elicits extensive activation across cortical and subcortical brain regions. However, transection of the auditory nerves or removal of cochlear fluids eliminates the US-induced activity, revealing an indirect auditory mechanism for US neural activation. Our findings indicate that US activates the ascending auditory system through a cochlear pathway, which can activate other non-auditory regions through cross-modal projections. This cochlear pathway mechanism challenges the idea that US can directly activate neurons in the intact brain, suggesting that future US stimulation studies will need to control for this effect to reach reliable conclusions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined., Approach: In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs., Main Results: We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations., Significance: These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.