The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.

Noninvasive and reversible modulation of neuronal activity in specific brain circuits may allow us to diagnose and treat brain disorders in, targeted ways. Low-intensity ultrasound, applied to the brain noninvasively, can be used to modulate neural activity with spatial specificity superior to other noninvasive methods such as transcranial electrical or magnetic stimulation (1–5). The neuromodulatory potential of ultrasound has been highlighted in studies that targeted peri-motor regions of anesthetized rodents or rabbits. Brief, low-intensity stimuli lead to observable movements of the limbs or other body parts (6–13).

However, the enthusiasm about the neuromodulatory potential of ultrasound has recently been dampened by studies that called these effects into question (14, 15). In addition, such overt effects have not been observed in large mammals including humans. Only small changes in neural signals (16–23) or small changes in reaction time or other metrics (24–26) have been found. Yet, to make it truly useful, the approach would ideally provide neuromodulatory effects that are strong enough to manifest in behavior. For example, if clinicians are to determine which brain circuits drive a patient’s craving for an addictive drug, the neuromodulatory effects on a particular neural circuit should be potent enough to yield measurable changes in the subject’s choice behavior, i.e., whether the subject decides to use the drug or not.