Guo, Hongsun2023-11-282023-11-282019-06https://hdl.handle.net/11299/258745University of Minnesota Ph.D. dissertation. June 2019. Major: Biomedical Engineering. Advisor: Hubert Lim. 1 computer file (PDF); xxxvii, 170 pages.Ultrasound (US) has shown to activate brain circuits, making it a promising noninvasive neuromodulation technique. However, little is known about the underlying mechanisms and neuromodulatory effects across different stimulus parameters. Here, we present research in which we applied transcranial US to different cortical regions and performed brain mapping studies in guinea pigs using extracellular electrophysiology. We observed that US elicits extensive activation across cortical and subcortical brain regions. However, transection of the auditory nerves or removal of cochlear fluids eliminated the US-induced activity, revealing an indirect auditory mechanism for US neural activation. This finding indicates that US stimulation of the brain predominantly activates the ascending auditory system through a cochlear pathway, which can activate other nonauditory regions through cross-modal projections. We then used similar approaches to study US modulatory effects on brain circuits in deafened animals. We observed that US induces localized suppression of somatosensory and visual evoked activity, which is associated with temperature rises in the brain tissue caused by US stimulation. This finding challenges the idea that US non-thermal effects are the only mechanism accounting for suppression of cortical activity by US stimulation. Whereas US activation of brain has been widely reported, activation of peripheral nerves by US have been reported with inconsistent results. Here, we show that US did not directly activate a mammalian sciatic nerve isolated from the surrounding tissue even at high pressures (1.3 to 5 MPa for different transducers) and various pulse patterns, but it could activate sensory structures (e.g., receptors in the skin or surrounding tissue) during stimulation of a non-isolated sciatic nerve, which could be mistakenly interpreted as direct activation of nerves (i.e., activation of the sensory structures leads to activation of peripheral nerves). We further demonstrated that US could reliably suppress nerve activity in vivo, depending on specific pulse durations (PDs), pressures, and center frequencies of US, with the observation that rises in tissue temperature caused by US stimulation drives greater suppressive effects. Maintaining the nerve temperature at a constant level prevents the suppression of nerve activity. These overall findings reveal that US can stimulate sensory structures rather than nerve fibers and that the US thermal effect is a major mechanism for suppression of nerve activity. Further improving our understanding of how US interacts with and modulates receptors, nerve fibers and cells within the brain will facilitate the development of new ultrasound-based neuromodulation therapies for various neurological and psychiatric disorders.enBrainHearingNeuromodulationNoninvasivePeripheralUltrasoundThesis or Dissertation