Browsing by Subject "Peripheral"
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Item Cerebral and peripheral hemodynamic responses to increased end-tidal carbon dioxide volumes(2015-03) Geijer, Justin RobertThough hypercapnia is a naturally occurring physiological state, it is generally accompanied by hypoxic conditions (Venkataraman et al., 2008). The convolution associated with concurrent changes in carbon dioxide and oxygen volumes offer unclear results to researchers investigating the effects of arterial gas changes (Brogan et al., 2003; Cinar et al., 2012). Researchers at the University of Toronto have developed a computer-controlled gas blender (RespirActTM, Thornhill Research, Toronto, Ontario, CA) capable of measuring and altering end-tidal gas volumes, which are indicative of arterial blood gas changes (Brogan et al., 2003; Cinar et al., 2012). Researchers have utilized this technology to investigate cerebral vascular reactivity (Kassner et al., 2010; Mandell et al., 2008; Mark et al., 2011; Prisman et al., 2008), but differing methodologies and a lack of reproducibility studies raise questions about the validity of the findings. In addition, the peripheral response to a hypercapnic, normoxic environment is not well documented. This dissertation will investigate the effects of a hypercapnic environment on the cerebral and peripheral vascular beds. We hypothesize that the vascular changes associated with a hypercapnic environment are repeatable in both the cerebral and peripheral beds. We further hypothesize that the cerebral vascular changes will occur more quickly than the peripheral changes. Lastly, we hypothesize that a comparison between hypercapnia-induced vasodilation of the brachial artery will provide a similar, but slower dilatory response than reactive hyperemia. The results of this dissertation may provide further insight into the mechanisms responsible for hypercapnia-induced vasodilation of the cerebral and peripheral blood vessels, and may provide repeatable methodologies to be utilized in future research.Item Identifying Parameters to Excite or Suppress Peripheral and Central Neurons Using Ultrasound for a New Noninvasive Neuromodulation Approach(2019-06) Guo, HongsunUltrasound (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.