Non-invasive ultrasound neuromodulation of human goal-directed behaviour

Objective

Many everyday scenarios require us to decide whether to persist or disengage from a course of action. For example, should we stay in a slow-moving supermarket queue or move to one that appears faster? In depressive disorders, these decisions are known to be altered, leading people to invest too little or too much effort in their goals. Despite their centrality to everyday behaviour, we lack a causal account of the neural and emotional mechanisms that shape these decisions. Neuroimaging implicates the nucleus accumbens and anterior insula, but as a correlational method, it cannot establish causality. Leveraging my expertise in ultrasound neuromodulation and clinical neuropsychology, I will address that gap by applying bilateral transcranial ultrasound stimulation (TUS) to these circuits in participants ranging from healthy volunteers to individuals with moderate depressive symptoms. Facial expressions and physiology (heart rate, pupil dilation, skin conductance) will provide a real-time index of emotion during decision-making. This fellowship will test TUS effects in a preregistered, double-blind, sham-controlled, within-subject study using a gamified decision-making task. Findings will advance causal understanding of how key brain circuits contribute to decisions to persist or disengage, identify emotional signatures that shape these decisions, and generate mechanistic targets for future interventions in depression. The fellowship, hosted by Prof Elsa Fouragnan at a leading centre for ultrasound neuromodulation, will consolidate international collaborations across Europe and the United States, develop my skills in computational modelling of behaviour, and accelerate my path to independence while building European capacity in translational mental health science.