LAUSR

We read with great interest the commentary titled, “Reversible Neuroinhibition Does Not Require a Thermal Mechanism” in response to our article “Reversible Neuroinhibition by Focused Ultrasound is mediated by a Thermal Mechanism.” [1]We are grateful that the authors highlight an important and complex point of ongoing discussion in the literature about the underlying mechanism(s) of FUS-mediated neuromodulation. There are some differences of interpretation that we are happy to address in a response. We measure significant suppression at temperature changes caused by US at around 1e2 Celsius. This is consistent with our interpretation of other’s work that temperature changes were relatively small. [2] Spivak et al. therefore interpret these results as not supporting the thermal hypothesis. Our claim is that even temperature changes at these magnitudes can cause significant suppression of neural activity as a signature of thermal activity. A major difference in our work is the chosen frequency of ultrasound. We use a 3.2 MHz carrier frequency due to its ability to provide high spatial resolution. Below are our results supporting that ultrasound-mediated thermal effect plays a significant role in neuromodulation: