Neural Simulation as a Neurocomputational Mechanism Underpinning Pathological Worry

Worry is the cardinal symptom of generalised anxiety disorder, which affects 6% of the population at any time. Worry may arise from altered functioning of the neurocomputational processes that simulate the future to adaptively avoid danger. My goals are to 1) characterise the neurocomputational processes that use “simulation” to enable avoidance, and 2) determine how changes in these processes are linked to pathological worry. I will use computational modelling, combined with neuroimaging, to reveal how simulations, supported by neural state reactivation, are used to guide decision-making in gamified avoidance tasks. Using state-of-the-art transcranial ultrasound stimulation and pharmacological manipulation, I will determine the causal role of neural circuits and their reliance on core neuromodulators. Finally, I will investigate the origins of aberrant simulation strategies, determining the influence of genetic risk and early-life stress, and testing the influence of real-world stress in adulthood. Later, I will link simulation processes to clinically significant worry, both in the lab and the real world, and investigate how to train more positive simulation strategies. Together, this work will provide insights into the processes supporting avoidance of danger, and indicate how these processes underpin pathological worry. Ultimately, these findings could inform the development of more targeted treatments.