Fig. 1

Approach for effective deep brain ultrasonic neuromodulation in humans. a Application to a patient with major depression. Programmatic electronic focusing is achieved using two sets of 126 individually controlled transducer elements, one over the left and one over the right side of the head. The subject’s head is secured in place using a standard radiological mask. Lateral windows are made within the mask for unobstructed ultrasound propagation. Coupling is mediated using cryogel. b Treatment validation. A standard Siemens flex coil was positioned over the subject’s head. Ultrasound was delivered into the target in 30-millisecond on periods (650 kHz, 1.0 MPa peak pressure) followed by 4-second off periods (0.8% duty). The on and off periods were presented in 1 minute ON blocks, followed by 1 minute OFF blocks of no ultrasound, for a total of up to 10 min (see also c). The MRI scanner acquired fMRI BOLD signals during the stimulation. The colorbar shows the t-statistic associated with the BOLD difference between the ON and OFF blocks. The white circles outline the approximate location of the SCC. c The modulation of the blood-oxygen-level-dependent (BOLD) signal by the ON and OFF ultrasound conditions. The fitted model (red) assumes standard hemodynamic response. d Control stimulation. To control for potential generic artifacts associated with ultrasound, we delivered a stimulus that had the same waveform and pressure amplitude as the stimulus focused into the SCC, but was unfocused (that is, the transducers emitted a plane wave)