Figure 4 -. Ultrasonic Neuromodulation and Sonogenetics.

(A) Illustration of focused ultrasound application to the brain and acoustic pulse parameters. CW, continuous wave; ISI, inter stimulus interval; PRF, pulse repetition frequency; PW, pulsed wave; SD, sonication duration; TBD, tone burst duration. (B) Top-down view of the brain showing acoustic intensity field of ultrasound beam targeting the S1 and sites 1 cm anterior (+1 cm) and posterior (−1 cm). (C) Time-frequency plots showing the power of evoked neural oscillations in the α, β, γ frequency bands in relation to the onset of ultrasound (dashed vertical line) and median nerve stimulation (solid vertical line) for sham and ultrasound treatment condition (B and C adapted with permission from Legon et al., 2014). (D) Left: acoustic intensity field targeting amygdala area of the primate brain. Right: functional connectivity fingerprint shows the strength of activity coupling between amygdala and other areas in control (blue), after ultrasound to amygdala (yellow), and after ultrasound to anterior cingulate cortex (ACC, red; adapted with permission from Folloni et al., 2019). (E) Diagram of experimental setup for in vitro neuronal ultrasound stimulation under acoustically realistic conditions. (F) GCaMP6f calcium signals in cultured neurons in response to ultrasound stimulation. Scale bar, 30 μm. (G) Biomolecular mechanisms of ultrasonic neuromodulation (E-G adapted with permission from Yoo et al., 2020). (H) Indirect excitation of mouse auditory cortex by FUS application to the visual cortex followed by widespread cortical response, as observed with wide-field calcium imaging (adapted with permission from Sato et al., 2018). (I) Neuronal responses to FUS recorded from guinea pig auditory or somatosensory cortex before and after deafening. (J) Mechanisms of indirect ultrasonic neuromodulation, where propagating ultrasound waves vibrate the cochlea, activating both auditory and non-auditory ascending pathways, leading to widespread activation. Deafening eliminates ultrasound-evoked multiunit sensory activity (I and J adapted from with permission from Guo et al., 2018). (K) Ultrasound activation of calcium signal in a C. elegans neuron engineered to express TRP-4 (adapted with permission from Ibsen et al., 2015).