Non-invasive Ultrasound Deep Neuromodulation of the Human Nucleus Accumbens Increases Win-Stay Behaviour

Abstract Current methods for directly modulating activity in deep human brain structures are limited and invasive. Here, we demonstrate modulation of activity in human deep brain structures using non-invasive transcranial ultrasound stimulation (TUS) and show it exerts selective effects on learning and decision making. 26 healthy adults participated in a within-subject repeated TUS– functional magnetic resonance imaging (fMRI) experiment with three sonication conditions. Participants performed a probabilistic learning task while undergoing fMRI scanning after counterbalanced 80 s 5 Hz repetitive TUS of the nucleus accumbens (NAcc), dorsal anterior cingulate cortex (dACC), or Sham. TUS-NAcc altered parametric BOLD response to reward expectation in NAcc and adjacent areas. Moreover, it induced changes specific to reward-related behaviours including in the use of win–stay strategy, learning rate following rewards, learning curve for choices of the rewarding option, and rate of repetition for rewarded choices. The results demonstrate TUS’s utility for human non-invasive deep-brain neuromodulation and the causal role of the human NAcc in learning from positive outcomes. Summary Precisely neuromodulating deep brain regions in humans could bring transformative advancements in both cognitive neuroscience and brain disorder treatment. In a within subject experiment, twenty-six healthy adults underwent a series of transcranial ultrasound stimulation procedures, including stimulation of the nucleus accumbens, the dorsal anterior cingulate cortex, or no sonication. Results revealed that ultrasound stimulation of the nucleus accumbens (NAcc) induced changes in reward-related behaviours, including in the tendency to stick with winning choices, the rate of learning specifically from positive feedback, and the rate of repeating rewarded choices. Functional brain scans showed corresponding neural changes in response to reward expectations in targeted and interconnected brain areas. These findings demonstrate the causal role of the human NAcc in learning from positive feedback, as well as the feasibility of using non-invasive neuromodulation deep in the human brain to modulate learning and decision making both as a research tool and as a potential component of future treatments for disorders involving reward sensitivity.