Reversible neuroinhibition does not require a thermal mechanism

We wish to respond to the recent publication by Darrow et al. titled “Reversible Neuroinhibition by FocusedUltrasound ismediated by a ThermalMechanism [1].” Specifically, wewish to alert the larger transcranial Focused Ultrasound Sonication (tFUS) community regarding inducing reversible neuroinhibition without thermal changes. Prior research has clearly demonstrated neuroinhibition without the temperature change suggested by Darrow et al. In a study attempting to suppress regional cortical excitability in rabbits, fMRI BOLD was used to monitor neural activity in the visual cortex after LED light stimulation [2]. Focused Ultrasound with a tone burst duration of 0.5 msec, Pulse repetition frequency1⁄4 100 Hz, and Isppa1⁄4 3.3 W/cm2 successfully suppressed the BOLD signal caused by light stimulation. The authors initially set out to confirm the accuracy of their targeting in rabbits using MR thermometry [3]. MR thermometry is based on the principle that the metrics used in MR-imaging (i.e. spin-lattice relaxation time, spin-spin relaxation time, proton density) are sensitive to temperature changes [3]. Specifically, the equation for measuring change in temperature caused by focused ultrasound stimulation can be given by DT1⁄4fðTÞ fðT0Þ gaB0TE