Transcranial focused ultrasound (tFUS) is an emerging tool for non-invasive neuromodulation that transmits low-intensity ultrasound through the skull to temporarily and safely modulate regional brain activity (Tyler, 2011). Ultrasound neuromodulation offers advantages over transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), such as better spatial resolution and the ability to reach deep targets in the brain (Fini and Tyler, 2017). tFUS reversibly modulates neuronal activity in rats (Tufail et al., 2010; Kim et al., 2014), sheep (Lee et al., 2016c), pigs (Dallapiazza et al., 2017), and monkeys (Downs et al., 2016).

In humans, tFUS has temporarily altered activity in somatosensory (Lee et al., 2016a), visual (Lee et al., 2016b), and thalamic brain regions (Legon et al., 2018). Researchers are interested in clinical applications of tFUS, including the treatment of psychiatric and neurological disease (Bystritsky and Korb, 2015; Monti et al., 2016). The current experiments investigated whether tFUS could modulate mood in healthy participants by sonicating a region in the prefrontal cortex implicated in emotional regulation, thereby uncovering a target for future therapeutic interventions (Experiment 1). The second experiment used resting-state functional magnetic resonance imaging (fMRI) to investigate FC changes after sonication of the prefrontal cortex to demonstrate that tFUS modulates brain function in networks related to emotional processing and mood.